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

Donation for ASPS Research in Honor of Kevin Kanai Griffith

iCureASPS thanks Liz Cooper, “Gamers For Good” and all the wonderful donors for the very generous donation of $15,000 aimed towards finding a cure for Alveolar Soft Part Sarcoma (ASPS). This donation helps to extend the collaboration of iCureASPS with the Dana Farber Cancer Institute in Boston, which has been ongoing since 2004.

Liz Cooper, President and Co-Founder of Gamers For Good, collected this donation through an 18-month art-book campaign. The campaign honored Kevin Kanai Griffith who was suffering from ASPS and sadly passed in October 2014.

The donation arrived just as we began plans for our 2016 research efforts.

Gamers for Good is a registered 501(c)(3) charity. Its mission is to provide charitable assistance to educate the general public about game development as a positive part of our society.
_____________________________________________________

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

Alveolar Soft Part Sarcoma Tumor Metabolizes Lactate by Goodwin and Jin et al in “Cancer Cell” Journal

Cancer Cell 26, 851-862, December 8,2014

The research from the group of Dr. Kevin Jones from the university of Utah was published in December 2014. It gives very important information on the metabolism of ASPS. It demonstrates that lactate drives proliferation of ASPS.

The full paper is available here.

The researchers initiated the study by creating transgenic mice carrying the ASPS gene in all of their cells. In patients this gene (ASPSCR1-TFE3) is found only in tumor cells. As expected this gene induced the formation of rapidly growing tumors. Unexpectedly, the ASPS tumors formed only in the heads of these mice. Every transgenic mouse developed a tumor within the skull, but never in the extremities (legs or hands) where usually patient ASPS tumors form. Close analysis of the tumors showed that these tumors had the same histopathology of human ASPS.

Next, the researchers identified the 500 most abundant genes expressed in the mice tumors and found them to be similar to those that were reported in human ASPS. As expected some of the genes are in pathways as “cell division” and “cell cycle”. However some of these genes belong to the “carbohydrate metabolism” pathway. This was another unexpected finding.

The surprise did not ended here: In addition to the fact that the ASPS in mice developed only in their heads, the researches found these tumors within skeletal muscles, although it was clear that the tumor origin did nor arise from muscle.

Then the researchers made few important findings explaining the above-unexpected observations. They found that the normal cells in the microenvironment of the tumors drove the formation of the tumors in the mice heads. The researchers discovered that ASPS tumors need the metabolite lactate for growth. Both brain and muscle are producing lactate flux. ASPS tumor cells then absorb this lactate and use this metabolic substrate as their energy source. Helping the ASPS tumors to uptake lactate are the MCT1 transporters and their binding partner CD147 protein. Those transporters are highly expressed by ASPS cells.

Finally, the researchers found that when they inhibited the lactate transporters MCT1 with a specific drug inhibitor namely CHC they could inhibit lactate signaling effects.

The researchers concluded that their research opened the door for exploring possible metabolic treatments for ASPS patients that could reduce the ability of ASPS to benefit from lactate which is available in their microenvironment.

 
_____________________________________________________

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

This Weekend Team ASPS Participated for the 12th Time in the PMC Bike Ride and Continues to Raise Funds to Sponsor Research on ASPS at the Dana Farber Cancer Institute in Boston

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Dear ASPS community, this weekend (August 1-2) Team ASPS participated for the 12th time in the Pan-Massachusetts Challenge (PMC).This is a bikea
thon that crosses Massachusetts to raise money for cancer research and clinical trials at the Dana-Farber Cancer Institute in Boston. Donations for Team ASPS are restricted for research on ASPS only.

I would like to remind that in 2005, following Team ASPS second ride we were able to initiate the GVAX cancer vaccine trial, which was developed by Dr. Glenn Dranoff. This was the first clinical trial ever that was dedicated for this very rare cancer.

We continue the research with Dr. George Demetri, Dr. Andrew Wagner, Dr. Massimo Loda and Dr. Ewa Sicinska at the Dana Farber. Those donations are helping us to learn more about ASPS and also
to inspire others in other research institutes to study ASPS. Our goal is to find the cure for our loved ones.

Please help us to find a cure for ASPS and please donate!
We are using our restricted account of the PMC for the collection of donation.

To donate online through the PMC website:

Please click on the following link: http://www.pmc.org/profile/YL002
This is Yosef Landesman ride page on the PMC website. Once you are on my personal page, click on “DONATE TO MY RIDE“.

Your donation is a fully tax refundable. The PMC tax ID is 04-2746912

Please let me know if you have any question. I thank you for your support.

Best Wishes, Yossi

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_____________________________________________________

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

Thank You Somerset Middle School!

Dear iCureASP Community,

I would like to thank the special students and teachers at Somerset Middle School in Wisconsin for their act of kindness and generosity. They made a decision to support the search for the much needed cure for Alveolar Soft Part Sarcoma.

Recently in my mailbox I found a donation with the following kind letter:

“Dear iCureASPS,

The students in my Family and Consumer Science class have a lab in which they are learning to measure and read a receipt. I have them make cookies and bars. Instead of eating them all we have a bake sale for the middle school students. The kids take a vote as to where the money will go. My class decided to have the proceeds from our bake sale go to iCureASPS, to help with research. One of my student’s brother does have this rare form of Cancer. Enclosed you will find a check for $397.45. Please use it to help wherever it is needed.

Sincerely,

Debbie Stevens
Somerset Middle School Family and Consumer Science Teacher”.

Special thanks to Sara Eichten, Principal of Somerset Middle School and to the parents who teach and educate their children to show good citizenship by actively performing acts of kindness.

Photo Somerset Middle School copy
______________________________________________________

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

Donate now and support the development of cure for ASPS

We are opening iCureASPS annual fundraiser with the traditional PMC bike ride. Our ASPS team rides yesterday and today for the 10th year at the Pan-Massachusetts Challenge (PMC). Ten years have passed since we founded our group and started to look for a cure for Alveolar Soft Part Sarcoma (ASPS), a rare cancer that has no cure and affects mainly young people.

The PMC is a bike-a-thon that crosses Massachusetts to raise money for cancer research and clinical trials at the Dana-Farber Cancer Institute in Boston. Members in our team ride this year 50, 90 or 140 miles between Wellesley to Cape Cod. Team ASPS set-up a restricted fund within the PMC. This restricted fund is aimed to achieve breakthrough in research and cure for Alveolar Soft Part Sarcoma.

Our goal this year is to initiate a new human clinical trial for ASPS patients in 2014 and WE NEED YOUR SUPPORT.

Team ASPS and iCureASPS already demonstrated that collaboration with the Dana Farber Cancer Institute is fruitful. Our collaboration resulted at the first ASPS clinical trial in 2005. This was the GVAX cancer vaccine clinical trial, which is under development by Dr. Glenn Dranoff.

Currently we are collaborating also with Dr. George Demetri, Dr. Andrew Wagner, Dr. Massimo Loda and Dr. Ewa Sicinska.

We hope to announce in 2014 the availability of a new clinical trial using a novel anti-cancer therapy.

There are two convenient ways to donate:
1. Online donations through the PMC website: Please click on the following link: Yosef Landesman ride page on the PMC website: (http://www.pmc.org/profile/YL0002). Then, once you are on my personal page, click on “DONATE TO MY RIDE”.

2. You can write a check payable to “PMC-Team ASPS YL0002”. Mail the check to:
Yosef Landesman
260 Tappan St.
Brookline, MA 02445

Your donation is a fully tax refundable. The PMC tax ID is 04-2746912
From the bottom of my heart I thank you for your support.

Best Wishes,
Yosef Landesman
______________________________________________________

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

The 9th PMC bike ride of “Team ASPS”: More donations for preclinical studies of Alveolar Soft Part Sarcoma

On the first weekend of August 2012, “Team ASPS” participated for the 9th time in the Pan-Massachusetts Challenge (PMC) bike ride. This bike-a-thon crosses Massachusetts to raise money for cancer research and treatment at the Dana-Farber Cancer Institute (DFCI) in Boston. Our team rode 90 miles and raised $30,705 specifically dedicated for finding a cure for ASPS.

Donation this year will specifically support preclinical testing of novel drugs for the cure of ASPS.
Dr. George Demetri, Dr. Andrew Wagner, Dr. Massimo Loda and Dr. Ewa Sicinska at the Dana Farber Cancer Institute in Boston conduct those preclinical studies and reserach.

I will continue to update you here on this website on the results of those efforts that were initiated almost 10 years ago.

Cure ASPS International thanks “Team ASPS”, our donors and to the ASPS community for all the relentless support for our efforts to find a cure for ASPS.

Below are Photos taken during the 2012 PMC bike ride. Best wishes for a Happy New Year!

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______________________________________________________

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