Update on Alveolar Soft Part Sarcoma Clinical and Preclinical Studies as Presented at the Annual Meeting of CTOS in November 8-11, 2017

Below are summaries of three clinical studies and one preclinical study on Alveolar Soft Part Sarcoma as were presented at the 2017 annual meeting of the “Connective Tissue Oncology Society” (CTOS) in November 8-11.

Please click the titles of each one of the 3 clinical studies to read more information on the “clinical Trials.gov” website.

  1. CASPS (CEDIRANIB IN ALVEOLAR SOFT PART SARCOMA), AN INTERNATIONAL RANDOMISED PHASE II TRIAL (NCT01337401) 

Ian Judson et al.,

Royal Marsden Hospital, London, United Kingdom

Objective: ASPS is rare (0.5-1% of soft tissue sarcomas), mainly affects young people and is unresponsive to conventional chemotherapy. Cediranib (C), a tyrosine kinase inhibitor (TKI), including vascular endothelial growth factor receptors, has shown significant activity in ASPS in single arm phase II trials. CASPS was designed to discriminate between the impact of C and the intrinsically indolent nature of ASPS.

Methods: CASPS compared C (30mg od) with placebo (P) in a 2:1 double blind randomization in pts age ≥16yrs with metastatic ASPS progressive in the previous 6 mths. Pts were unblinded at wk 24 or progression if sooner when those on P crossed over to C. The primary endpoint of % change in the sum of target marker lesions (TMLsum) between baseline and wk 24 or progression if sooner was compared between groups by Mann-Whitney test. Secondary endpoints were progression-free survival (PFS), wk 24 response rate (RR) and best response (RECIST v1.1), safety/tolerability, overall survival (OS). One-sided p-values and two-sided 90% condense intervals are reported.

Results: 48 pts were recruited between 07/2011 and 07/2016 from 12 sites (UK, Australia & Spain). 52% pts were female, median age 31. Most common grade ≥3 AEs on C were hypertension (19.4%), raised gamma GT (6.5%), diarrhoea (6.5%), asthenia (3.2%) and fatigue (3.2%), which were manageable by dose reduction. In the evaluable population (N=44) median change in TMLsum on C was −8.3% (IQR −26.5% to +5.9%) vs P: +13.4% (IQR −0.6% to +23.1%), one-sided p=0.0010. Best response by wk24 was partial response (PR) in 6/28 (21%) pts on C vs 0/16 on P (one-sided p=0.053), giving a RR of 21%. At wk24 3 pts were still in PR and 14 had stable disease, giving a 6 mth clinical benefit rate (CBR) of 61%. At the time of analysis 3 pts remained in PR with median response duration of 26+mths. The HR for PFS (C vs P) was 0.58 (90%CI 0.33-1.03, one-sided p=0.059), median PFS was 10.8 mths on C vs 3.7 mths on P. The HR for OS was 0.66 (95%CI 0.25-1.75) p=0.41. OS at 12mths was C: 94%; P: 66%, in spite of crossover. 12 C pts had received a prior TKI; this had no major impact on PFS.

Conclusion: CASPS confirms the activity of C in ASPS shown in previous trials. CASPS met its primary endpoint of a significant change in TMLsum at week 24 for C compared with P. There was a 7-month improvement in median PFS. Tumor tissue and serial blood samples will be analyzed for predictive and prognostic biomarkers. 

 

  1. ANTITUMOR ACTIVITY OF AXITINIB PLUS PEMBROLIZUMAB IN A PHASE II TRIAL FOR PATIENTS WITH ADVANCED ALVEOLAR SOFT PART SARCOMA (ASPS) AND OTHER SOFT TISSUE SARCOMAS (NCT02301039)

Breelyn A. Wilky et al.,

University of Miami Miller School of Medicine, Miami, FL, USA

Objective: Inhibition of programmed-death 1 (PD1) by pembrolizumab (P) monotherapy produced overall response rates (ORR) of 19% in SARC028, a Phase II study in advanced soft tissue sarcomas (STS). Vascular endothelial growth factor (VEGF) promotes accumulation of suppressive immune cell phenotypes and cytokines. Combinations of anti-VEGF receptor tyrosine kinase inhibitors (VEGFR-TKI) with checkpoint inhibitors increased immune cell infiltration and showed promising anti-tumor activity in other solid cancers. Axitinib (Ax) is a pan-VEGFR TKI with favorable progression-free survival (PFS) reported in Axi-STS, with acceptable toxicity in combination with P in renal cell carcinoma. We report initial toxicity and efficacy results of combination Ax plus P for patients (pts) with advanced STS.

Methods: We designed an open-label single institution Phase II trial of Ax plus P in 30 pts with advanced or metastatic STS, requiring radiographically progressing disease, adequate end-organ function and performance status. Pts received Ax at 5 mg PO twice daily with intra- patient dose escalation according to predefined toxicity thresholds, and concurrent P 200mg IV q21 days. Primarily endpoint was progression-free rate at 3 months (PFR), with secondary endpoints of toxicity, ORR, PFS, and overall survival. All patients underwent mandatory tumor biopsies and peripheral blood sampling for correlative immunoprofiling at baseline, 12 weeks and at progression.

Results: 28 of 30 pts have accrued to date. Enrolled sub- types: ASPS (29%), UPS (18%), LMS (21%), and other (29%). 3-month PFR by RECIST 1.1 for 18 evaluable pts was 56%, and 4 pts (22%) achieved partial response (PR). Responders include 3/3 (100%) currently evaluable ASPS pts (median tumor size decrease of 70%), and 1 pt with non-uterine LMS (tumor size decrease 55%). Clinical benefit was observed in 3 pts with RECIST progression at 3 months, suggesting a need for alternative response criteria such as Choi criteria. Ax plus P was overall well-tolerated, with P-related grade 3/4 toxicities in 3 pts (autoimmune hepatitis, arthritis and hyperglycemia), and Ax-related grade 3/4 toxicities in 2 pts (hypertriglyceridemia, spontaneous pneumothorax).

Updated response and toxicity data will be presented. Correlative immuno- profiling is ongoing.

Conclusion: Combination Ax plus P is feasible and well-tolerated, and shows early evidence of activity, particularly in ASPS pts. Clinical trial information: NCT02301039.

 

  1. A PHASE 2 TRIAL OF CABOZANTINIB (XL184) IN METASTATIC REFRACTORY SOFT TISSUE SARCOMA (NCT 01755195) 

Alice Chen et al.,

National Cancer Institute, Bethesda, MD, USA

Objective: Soft tissue sarcomas (STS) are a rare group of tumors (~1 % of adult cancers) arising mainly from embryonic mesoderm. Increased expression of VEGF and MET has been reported both in sarcoma cell lines and patients (pts) with STS. Cabozantinib, a multi-kinase inhibitor of MET, VEGFR2, AXL, RET, ROS1 is approved for treatment of renal cell carcinoma and medullary thyroid cancer. Dual targeting of VEGF and MET pathways with cabozantinib is hypothesized to result in clinical benefit for pts with STS. We are conducting a 2-stage, open-label, phase II trial of cabozantinib monotherapy (NCT 01755195) evaluating a dual-endpoint of response rate (CR+PR) of 30% vs. 10%, and a 6-month PFS rate of 65% vs 45% in pts with STS. Secondary objectives include measuring circulating levels of HGF, VEGF-A, soluble VEGFR2 (sVEGFR2), and soluble MET (sMET) pre- and post-treatment, which will be collected in the second stage pts.

Methods: Cabozantinib is administered orally at 60 mg po qd for 28d cycles. Eligibility criteria includes pts ≥18 years; ECOG PS ≤ 1, adequate organ functions. No cavitating mass or vessel-encasing lesions are permitted. Antitumor responses are determined using RECIST 1.1 criteria.

Results: The study has accrued 27 pts at NCI (Alveolar soft part sarcoma (ASPS) (6), leiomyosarcoma (5), clear cell sarcoma (3), liposarcoma (2), synovial sarcoma (2) and one each of embryonal sarcoma, MPNST, myxoid chondrosarcoma (MC), myoepithelioma, myxoid cell sarcoma, GIST). At time of analysis, 5 pts remain on study. Time on study 7-47 months. Four pts have confirmed PRs (2 ASPS, 1 liposarcoma, 1 MC); time to PR was 4 – 22 months and response duration averaged 39 months. Twelve pts have SD for six months. Median PFS was 9.6 months. Drug related grade 3/4 adverse events include 5 HTN (21%), 3 neutropenia (13%), 2 abdominal pain (8%), 2 lipase elevation (8%), 2 thromboembolic events (8%), and one each (4%) of left ventricular dysfunction, alkaline phosphatase elevation, enterocolitis, fatigue, mu- cositis, nausea, hand-foot syndrome, transaminitis. 8 pts required dose reductions, including 2 reductions in 3 pts.

Conclusion: This is the first phase II study of cabozantinib in STS. Having met our first stage response objective, we are accruing at multi-sites with plans to assess a total of 50 patients.

 

  1. AUTOPHAGY IN ALVEOLAR SOFT PART SARCOMA CONFERS MECHANISMS OF RESISTANCE TO CHEMOTHERAPY

Jared J. Barrott & Kevin B. Jones,

University of Utah, Salt Lake City, UT, USA

Objective: Altered metabolism is considered to be one of the new hallmarks of cancer. Autophagy is one major avenue of altered cancer metabolism, enabling cell survival under metabolic stress and promoting chemoresistance. The nuclear localization of MiTF/TFE3 family transcription factors has associated with upregulated transcription of autophagy genes in pancreatic cancer. Alveolar soft part sarcoma is a rare but deadly soft-tissue sarcoma, with a predilection for adolescent and young adult victims. Alveolar soft part sarcoma is noteworthy for its resistance to traditional cytotoxic chemotherapies. It consistently associates with a t(X;17) chromosomal translocation that produces the ASPSCR1-TFE3 target gene, bearing the DNA-binding domain from TFE3 and protein interaction domains from ASPSCR1. We have demonstrated that conditional expression of ASPSCR1-TFE3 is sufficient to drive alveolar soft part sarcomagenesis in the mouse with complete penetrance. Mouse tumors recapitulate human alveolar soft part sarcoma histology and transcriptomes faithfully. While the direct targets of ASPSCR1-TFE3 have been studied in a renal cell carcinoma cell line, they have not been studied in alveolar soft part sarcoma. Our objective was to identify the direct targets of ASPSCR1-TFE3 and how these targets confer resistance to doxorubicin.

Methods: The human cell lines expressing ASP-SCR1-TFE3, ASPS-1 and FUUR-1, as well as mouse tumors driven by expression of ASPSCR1-TFE3 were subjected to nuclear fractionation and chromatin immunoprecipitation using antibodies against ASPSCR1 and RNAPol2. Cells and tumors were further characterized for their presence of auotphagic flux by detection of LC3-II and abundance of lysosomal proteins LAMP1 and CTSD. Cell lines were treated with combination therapy using the autophagy inhibitor, chloroquine, and doxorubicin and compared to monotherapy and controls. Viability was assessed as well as changes in mitochondria, ROS production, and apoptosis. Furthermore, cells were analyzed by gas-chromatography mass spectrometry (GC-MS) for metabolites involved in cellular respiration and glycolysis. Lastly, mice were treated with either control, monotherapy of chloroquine (15 mg/kg) or doxorubicin (10 mg/kg), or combination therapy for up to 5 months. Mice on combination therapy showed a statistical improvement in survival of 3 months over control and doxorubicin treatments.

Results: We report not only the first genome-wide localization of the ASPSCR1-TFE3 oncoprotein on chromatin from alveolar soft part sarcoma cell lines and mouse tumors, but also its association with actively transcribed genes. Among these are found many genes related to autophagy, especially those related specifically to the nutrient responsive pathways that drive autophagy. We demonstrate high expression of autophagy-related lysosomes and proteins at baseline conditions in human tumors and cell lines and mouse tumors. We also demonstrate active autophagic flux even in the absence of stress conditions. Inhibition of autophagy has no apparent impact on survival of alveolar soft part sarcoma cells alone, but profoundly impacts their protein degradation pathways and the availability of amino acids for protein assembly in stress. Inhibition of autophagy strongly synergizes with chemotherapy to kill alveolar soft part sarcoma cells, suggesting it was a source mechanism for resistance. Furthermore, mice treated with combination therapy of autophagy inhibition and chemotherapy significantly extends life 3 months beyond control and single agents alone.

Conclusion: We have therefore demonstrated the direct targets of ASPSCR1-TFE3 in alveolar soft part sarcomas, including a number of autophagy genes that are expressed in these tumors, independently from nutrient deprivation or stress, rendering cells particularly resistant to many therapy-induced stresses. Inhibition of autophagy in alveolar soft part sarcoma causes the tumor cells to be more susceptible to chemotherapeutic stress.

_____________________________________________________

Yosef Landesman, Ph.D.
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail: landesmany@yahoo.com

New ASPS Trial: A​​PROMISS – A Phase III Trial of Anlotinib for Patients with Alveolar Soft Part Sarcoma and Other Sarcomas

OPEN NOW: ​​​APROMISS – A Phase III Study of AL3818 (Anlotinib) Hydrochloride Monotherapy in Subjects With Metastatic or Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma and Synovial Sarcoma​​

Sponsored by: ​Advenchen Laboratories, LLC.

ClinicalTrials.gov Identifier: ​NCT03016819

​Anlotinib (AL3818), a tyrosine kinase inhibitor, is an investigational drug being evaluated in the treatment of ​Alveolar ​Soft ​Part ​Sarcoma​ and other sarcomas. ​Anlotinib was studied in ​soft tissue sarcomas in a phase 2 trial and demonstrated encouraging results in ​Alveolar ​Soft ​Part ​Sarcoma. The results were presented at the ASCO 2016 annual meeting. The promising phase 2 results paved the way for APROMISS, the phase 3 study, which is currently open to recruitment in the United States with plans to open globally in Japan and Europe.

The objective of APROMISS is to assess the effectiveness and safety of ​Anlotinib in subjects with metastatic or advanced​ Alveolar ​Soft ​Part ​Sarcoma​ and other sarcomas. The FDA also granted orphan drug designation to ​Anlotinib for the the potential treatment of soft tissue​ sarcoma, designation which is granted for drugs intended for diseases or conditions that affect fewer than 200,000 people in the United States.

Eligibility: Individuals​ 18 years of age and older with​ locally advanced or metastatic ​Alveolar ​Soft ​Part ​Sarcoma​ who are not candidates for surgical resection​. Please note that other eligibility criteria do apply – for further details please go to​ the ClinicalTrials.gov page at​ ​https://clinicaltrials.gov/ ct2/show/NCT03016819.

Contact:

​Melissa Chen ​at: melissac@advenchen.com​

Judy Chen ​at:​ judyc@advenchen.com

Locations: ​Miami, FL; Ann Arbor, Michigan; Los Angeles, CA; Stanford, CA

_____________________________________________________

Yosef Landesman, Ph.D.
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail: landesmany@yahoo.com

Anlotinib Shows Efficacy in ASPS Patients in Phase II Study in China

A presentation is the recent annual meeting of the American Society of Clinical Oncology (ASCO) conference in Chicago highlighted the new drug Anlotinib and its efficacy in treating Alveolar Soft Part Sarcoma patients. Anlotinib is a new receptor tyrosine kinase inhibitor, currently in phase II clinical trials in China. Patients with different types of soft tissue sarcomas were treated with the drug. Thirteen of the patients were Alveolar Soft Part Sarcoma patients.

Interestingly, best activity was measured in Alveolar Soft Part Sarcoma patients.

Currently Anlotinib is used in several clinical trials in China and in the USA:

USA:

  1. A Phase 1/2a Evaluation of the Safety and Efficacy of Adding AL3818 to Standard Platinum-Based Chemotherapy (AL3818-US-002) (AL3818)
  2. A Phase 1/2a Evaluation of the Safety, Pharmacokinetics and Efficacy of AL3818 in Subjects With Recurrent or Metastatic Endometrial, Ovarian or Cervical Cancer (AL3818-US-001)

China:

  1. Study of Anlotinib in Patients With Soft Tissue Sarcoma(STS)(ALTER0203)
  2. Study of Anlotinib in Patients With Esophageal Squamous Cell Carcinoma (ALTER1102)
  3. Study of Anlotinib in Patients With Metastatic Colorectal Cancer(mCRC)(ALTER0703) (ALTER0703)
  4. Study of Anlotinib in Patients With Medullary Thyroid Carcinoma(ALTER01031)
  5. A Phase I Additional Study of Anlotinib on Tolerance and Pharmacokinetics
  6. Study to Investigate the Absorption, Metabolism and Excretion of [14C] Anlotinib in Patients With Advanced Cancer Patients
  7. Study of Anlotinib in Patients With Differentiated Thyroid Cancer(ALTER01032)
  8. Study of Anlotinib in Patients With Gastric Cancer(ALTER0503)
  9. A Study of AL2846 on Tolerance and Pharmacokinetics

Here below is the full abstract as was presented at the June 2016 annual conference of the American Society of Clinical Oncology (ASCO) in Chicago:

Phase II study of anlotinib for treatment of advanced soft tissues sarcomas

Abstract Number: 11005

Citation: J Clin Oncol 34, 2016 (suppl; abstr 11005)

Author(s): Yihebali Chi,  Sun Yongkun et al.,

Abstract: 

Background: No standard therapies are available in China for Soft tissues sarcomas (STS)patients who failed to chemotherapies. Anlotinib is a multi-target RTK inhibitor, with VEGFR1/2/3, FGFR1/2/3, PDGFRα/β, c-Kit, Ret ect. Recommended dose in phase I is 12 mg daily, 2 weeks on/1 week off. This single-arm, multi-center phase II study (NCT01878448) to assess efficacy and safety of Anlotinib for treatment of STS patients who failed to conventional therapies.

Methods: Pathological types of advanced STS mainly include malignant fibrous histiocytoma (MFH), liposarcoma, leiomyosarcoma, synovial sarcoma (SS) and other sarcomas, but excluding RMS, chondrosarcoma, GIST etc. Patients with measurable indicators (RECIST1.1) were treated with Anlotinib. Efficacy was assessed every 6 weeks. The primary endpoint was disease PFR at week 12 (PFR12w ).

Results: From April 2013, we recruited 166 patients in 15 centers in China, including 100 males and 66 females, average age is 44 (15-70). Pathological types included SS (n=47), leiomyosarcoma (n=26), fibrosarcoma (n=18), MFH (n=19), alveolar soft part sarcoma (ASPS, n=13), liposarcoma (n=13), others (n=30). As of May 2015, 154 patients were assessable for efficacy: PFR12w was 57.23%, mPFS was 5.63 months.22 patients achieved PR over time (19 pts confirmed, and ORR was 11.45%. See below table. 166 patients were assessable for safety. Common grade III/IV AEs include: hypertension(n=8), pneumothorax(n=5), thyroid hypofunction(n=2), proteinuria(n=1), hand-foot-skin reaction(n=1), diarrhea(n=1), triglyceride increase (n=2), hyperglycemia (n=1). 24 patients (14.5%) had dose adjustment during treatment, reducing to 10 mg daily, 2 weeks on/1 week off.

Conclusions: Anlotinib is effective to many pathological types of soft tissue sarcoma, particularly to ASPS and SS. Overall PFR12w reached 57.23%. Meanwhile, Anlotinib is well tolerated, while pneumothorax needs to be noticed. A randomized, controlled clinical trial is ongoing.

Yihebali Chi and Sun Yongkun contributed equally to this work. Clinical trial information: NCT01878448

 

Case (n) Response Rate (%) Progression free survival Rate (12w) %
Overall 166 11.45 57.23
SS 47 12.77 63.83
leiomyosarcoma 26 7.69 69.23
fibrosarcoma 18 11.11 61.11
MFH 19 5.26 47.37
liposarcoma 13 7.69 53.83
ASPS 13 46.15 76.92
others 30 3.33 33.33

_____________________________________________________

Yosef Landesman, Ph.D.
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail: landesmany@yahoo.com

New ASPS Clinical Trial: Axitinib and Pembrolizumab in Subjects With Advanced Alveolar Soft Part Sarcoma and Other Soft Tissue Sarcomas

New clinical trial for ASPS is expected to open on March 2016.

Study number: NCT02636725

This is a phase II clinical trial that combines treatment with Axitinib and Pembrolizumab in patients with advanced Alveolar Soft Part Sarcoma (ASPS) and other soft tissue sarcomas.

Axitinib (AG013736; trade name Inlyta) is a small molecule tyrosine kinase inhibitor.

Pembrolizumab (formerly MK-3475 and lambrolizumab, trade name Keytruda) is an antibody used in cancer immunotherapy to target the programmed cell death 1 (PD-1) receptor.

Patients will be treated with twice daily dosing of axitinib alone for the first 7 days, followed by concurrent axitinib administered twice daily at 5 mg orally (PO), plus intravenous administration of pembrolizumab every 21 days. Patients will be assessed every three weeks for toxicity.

The study will include up to 30 patients

Contact information:

Breelyn Wilky, MD, University of Miami
Phone: 305-243-1287
e-mail: b.wilky@med.miami.edu
_____________________________________________________

Yosef Landesman, Ph.D.
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail: landesmany@yahoo.com

Important Announcement: CASPS – A Phase II Trial of Cediranib in the Treatment of Patients with Alveolar Soft Part Sarcoma

OPEN NOW: CASPS – A Phase II Trial of Cediranib in the Treatment of Patients with Alveolar Soft Part Sarcoma

Sponsored by: The Institute of Cancer Research / The Royal Marsden NHS Foundation Trust

Information provided by: The Institute of Cancer Research – Clinical Trials and Statistics Unit

ClinicalTrials.gov Identifier: NCT01337401

Cediranib (AZD2171) is a new, unlicensed drug that has been studied in the laboratory and clinic, and researchers think it could slow the spread of ASPS. CASPS is a small clinical trial investigating cediranib in the treatment of ASPS, which is currently open to recruitment in the UK, Australia and Spain. Further information on CASPS and a list of hospitals involved in the trial can be found at http://cancerhelp.cancerresearchuk.org/trials/a-trial-cediranib-alveolar-soft-part-sarcoma-casps.
Objective: The aim of this study is to see if cediranib (AZD2171) can help people with alveolar soft part sarcoma.

Eligibility: Individuals 16 years of age and older who have been diagnosed with alveolar soft part sarcoma. Please note that other eligibility criteria do apply – for further details please go to http://cancerhelp.cancerresearchuk.org/trials/a-trial-cediranib-alveolar-soft-part-sarcoma-casps.

Contact: Professor Ian Judson: casps-icrctsu@icr.ac.uk

Locations: United Kingdom, Australia, Spain
______________________________________________________

Yosef Landesman, Ph.D.
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail: landesmany@yahoo.com

A Summary of Phase II Cederanib Clinical Trial

The summary of the phase 2 clinical trial of Cediranib on Alveolar Soft Part Sarcoma was recently published in the “Journal of Clinical Oncology” by Shivaani Kummar and others from the National Cancer Institute and the Frederick National Laboratory for Cancer Research.

The authors report that Cediranib has substantial single-agent activity, producing an objective response rate of 35% and a disease control rate of 84% at 24 weeks of treatment. On the basis of these results, they report on the opening of an “open-label, multicenter, randomized” phase II registration trial for patients with metastatic ASPS comparing Cediranib with Sunitinib, which is another VEGFR inhibitor. 

Below is the abstract from this important scientific publication: 

Purpose

Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor, for which no effective standard systemic treatment exists for patients with unresectable disease. Cediranib is a potent, oral small-molecule inhibitor of all three vascular endothelial growth factor receptors (VEGFRs). 

Patients and Methods

We conducted a phase II trial of once-daily cediranib (30 mg) given in 28-day cycles for patients with metastatic, unresectable ASPS to determine the objective response rate (ORR). We also compared gene expression profiles in pre- and post-treatment tumor biopsies and evaluated the effect of cediranib on tumor proliferation and angiogenesis using positron emission tomography and dynamic contrast-enhanced magnetic resonance imaging. 

Results

Of 46 patients enrolled, 43 were evaluable for response at the time of analysis. The ORR was 35%, with 15 of 43 patients achieving a partial response. Twenty-six patients (60%) had stable disease as the best response, with a disease control rate (partial response + stable disease) at 24 weeks of 84%. Microarray analysis with validation by quantitative real-time polymerase chain reaction on paired tumor biopsies from eight patients demonstrated downregulation of genes related to vasculogenesis. 

Conclusion

In this largest prospective trial to date of systemic therapy for metastatic ASPS, we observed that cediranib has substantial single-agent activity, producing an ORR of 35%

Click here to download the full publication.

______________________________________________________

Yosef Landesman, Ph.D.
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail: landesmany@yahoo.com

Update on the Sunitinib or Cediranib for Alveolar Soft Part Sarcoma

If you consider to join the following clinical trial: Sunitinib or Cediranib for Alveolar Soft Part Sarcoma ; study NCT01391962

Please note that patients can join only if:

·        Patients show evidence of disease progression

·        Patients must not have received prior treatment with any VEGF receptor tyrosine kinase inhibitor (e.g., cediranib, sunitinib, pazopanib, sorafenib); however, pre-treatment with bevacizumab is allowed.

Please also note that

·        Patients in this trial will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles.

·        If and when disease progression is seen, then patients will cross over to the other treatment arm after a 2-week wash-out period.

Contacts

Deborah E Allen, R.N.                 (301) 402-5640                 allendeb@mail.nih.gov

Shivaani Kummar, M.D.               (301) 496-4916                 kummars@mail.nih.gov

  

Locations in the United States:

1.   California Santa Monica Oncology Center

Santa Monica, California, United States, 90403

2.    Maryland, National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, United States, 20892

Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office:     (888) NCI-1937

3.   Massachusetts, Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02115

4.   New York, Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10021

5.   Texas, MD Anderson Cancer Center

Houston, Texas, United States, 77030-4096

We hope that the study will be conclusive and finally the first effective therapy for ASPS will be validated and then be available for all ASPS patients.

Best Wishes,
Yosef Landesman
______________________________________________________

Yosef Landesman, Ph.D.
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail: landesmany@yahoo.com

Important Update on Cediranib development for Alveolar Soft Part Sarcoma (ASPS)

Dear ASPS community. Many of our patients who participated in Cediranib clinical trials reported on our FORUM positive ASPS response to the drug. The conclusion that Cediranib shows favorable activity in ASPS is detailed in a summary of a Phase 2 clinical trial by Dr. Kummar in the 2011 meeting of the American Society of Clinical Oncology (ASCO). According to this study that included 36 ASPS patients, “Cediranib has substantial single-agent activity in ASPS, with a > 40% response rate and a disease control rate of 78%”. Those are very exciting news for us as so far no other drug showed efficacy in ASPS.

However, recently we learned that AstraZeneca, the developer of Cediranib has decided to transfer the development of Cediranib to the National Cancer Institute (NCI). AstraZeneca transferred 100 kg of Cediranib to the NCI for that purpose and the NCI opened a new Phase 2 clinical trial for ASPS patients. The goal of the new NCI trial is to confirm the early Phase 2 results and to compare Cediranib to Sunitinib, another drug that was tested on 9 ASPS patients at the Istituto Nazionale Tumori, Milan, Italy. The Sunitinib study showed partial response in 5 of the 9 ASPS patients.

The good news are that there is a possibility that one of the drugs will be selected and then be available for ASPS patients.

The new Cediranib and Sunitinib Phase 2 clinical trial is now open in California: Santa Monica Oncology Center, Maryland: NIH/NCI Bethesda, Massachusetts: Dana Farber and Texas: MD Anderson.

The NCI is making efforts to make sure that the study will be conclusive. Therefore travel and additional support will be given to every ASPS patient who participates in the trial in the NCI. The NCI will accept and pay travel also for ASPS patients who are not US residents. NonUS residents need to arrive to any US port and then their flight to the NCI, their treatment and minimal stay will be paid by the NCI!

For full details please click and read the details in the following link: Sunitinib or Cediranib for Alveolar Soft Part Sarcoma. For more information, contact the NCI Referral Office at 1-888-NCI-1937, the study number is: NCT01391962.

We hope that the study will be conclusive and finally the first effective therapy for ASPS will be validated and then be available for all ASPS patients.

Best Wishes,
Yosef Landesman
______________________________________________________

Yosef Landesman, Ph.D.
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail: landesmany@yahoo.com

Update on the Cediranib and Sunitinib Clinical Trials for Alveolar Soft Part Sarcoma Phase II in the USA

  Please note the two Phase II clinical trials available for ASPS patients in the US:

1.   Sunitinib or Cediranib for Alveolar Soft Part Sarcoma, study number NCT01391962

Contact: NCI Referral Office, Tel.   1-888-NCI-1937

Locations:

United States, California
Santa Monica Oncology Center
Santa Monica, California, United States, 90403

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892

United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115

United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030-4096

2.   Cediranib (AZD2171) in Patients With Alveolar Soft Part Sarcoma, study number NCT00942877

Contact:

Agnes T. Strassberger, R.N.    Tel.  (301) 435-5664,   e-mail:  agnes.strassberger@nih.gov

Location:

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892

______________________________________________________

Yosef Landesman, Ph.D.
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail:
landesmany@yahoo.com

 

New Clinical Trial for Alveolar Soft Part Sarcoma in the United Kingdom: CASPS – A Phase II Trial of Cediranib

Dear ASPS Community,

We are very happy to report the opening of another clinical trial for ASPS patients in the United Kingdom. This new clinical trial is a phase II trial of Cediranib. Every trial brings with it the hope for cure!

ASPS patients who are trying Cediranib are sharing their experience on iCureASPS Forum. I would encourage everyone to click here and read comments and discussions of those patients. Please use our website, read and study well! Share information and communicate.

Best Wishes to everyone and thank you very much Dr. Judson and all who are working with you for taking the lead on this clinical trial.

Yosef Landesman, Ph.D.

President & Cancer Research Director

e-mail: landesmany@yahoo.com

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CASPS – A Phase II Trial of Cediranib in the Treatment of Patients with Alveolar Soft Part Sarcoma

Sponsored by: The Institute of Cancer Research / The Royal Marsden NHS Foundation Trust

Information provided by: The Institute of Cancer Research – Clinical Trials and Statistics Unit

ClinicalTrials.gov Identifier: NCT01337401

Cediranib (AZD2171) is a new, unlicensed drug that has been studied in the laboratory and clinic, and researchers think it could slow the spread of ASPS. CASPS is a small clinical trial investigating cediranib in the treatment of ASPS, which is currently open to recruitment in the UK. Further information on CASPS and a list of hospitals involved in the trial can be found at:

http://cancerhelp.cancerresearchuk.org/trials/a-trial-cediranib-alveolar-soft-part-sarcoma-casps.

Objective: The aim of this study is to see if cediranib (AZD2171) can help people with alveolar soft part sarcoma.

Eligibility: Individuals 16 years of age and older who have been diagnosed with alveolar soft part sarcoma. Please note that other eligibility criteria do apply – for further details please go to:

http://cancerhelp.cancerresearchuk.org/trials/a-trial-cediranib-alveolar-soft-part-sarcoma-casps.

Contact: Professor Ian Judson, casps-icrctsu@icr.ac.uk

Locations: United Kingdom