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

__________________________________________

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

Tumor Expression Profile of Alveolar Soft Part Sarcoma May Pave the Way for New Treatments at The Dana Farber Cancer Institute

Scientists from the group of Dr. Massimo Loda reported the results of an extensive study that aims to identify potential therapeutic targets for ASPS last Friday.

The research team, comprised of Shamini Selvarajah (PhD), Eleanor Chen (MD, PhD), and Saumyadipta Pyne (PhD), used cDNA microarray technology (gene expression array) to examine the expression of 18,401 genes in primary, and metastatic ASPS tumors from 14 ASPS patients. The work was done in collaboration with Brigham and Women’s Hospital, and the Broad Institute, affiliated with the Massachusetts Institute of Technology, and Harvard University.

Significant gene expression changes were discovered in 1,063 genes. The team elected to focus on 323 of them, which were singled out for their dramatically increased (or decreased) expression from the time the ASPS tumor was a primary (original tumor) to the time it turned into a metastasis. In other words, this work identified genes (those genes turn into proteins in the tumor) that changed their expression, as the tumor increased in aggressiveness. Such genes are well suited to be targeted as a therapeutic modality. Initial analysis of those genes points to several known molecular pathways that contribute to tumor growth and angiogenesis (formation of new blood vessels) in other types of cancers. The next challenge will be to identify the most promising target genes, for which approved drugs already exist. As an initial next step, these drugs could then be tested in animal tumor models of ASPS, and in ASPS cell lines.

Dr. Glenn Dranoff is an active participant, and collaborator in this project. Dr. Dranoff developed the GVAX vaccine, and ran the first GVAX clinical trial for ASPS patients. He will continue to be involved in the efforts to find a cure for ASPS.

Dear ASPS patients, friends and family members! We need your help to continue supporting the science behind results like this one. Through cutting edge research, more groundbreaking findings will be made that will bring a cure for ASPS. You can help, and be part of these great efforts.

Please:

1.   Consider fund-raising and donations to support the efforts to find a cure for ASPS at the Dana-Farber Cancer Institute.

2.   Encourage patients who are planning surgeries to donate their tumors to the Dana Farber.

3.   Communicate with me in regards to both of the above to ensure that funds and tumor donations reach their destination.

We are thankful to Dr. Massimo Loda and the scientists who did this important work, Dr. Glenn Dranoff, Dr. Ewa Sicinska, and the administrative staff Marcia Izzi and Laurie Peterson.

iCureASPS will continue to support these studies through direct funding, and through Team ASPS with the Pan Mass Challenge, as we believe that this is the way to discover the much needed cure!

2010_asps_reseach_04.JPG2010_asps_reseach_01.jpg 2010_asps_reseach_02.jpg 2010_asps_reseach_03.JPG

______________________________________________________

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