ADI-PEG 20 + Chemotherapy for Leiomyosarcoma

Recruiting in Palo Alto (17 mi)

+29 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Polaris Group

Must not be taking: Antiretrovirals, Immunosuppressants

Disqualifiers: Brain metastases, Uncontrolled illness, HIV, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

To compare the efficacy and safety in subjects with advanced or metastatic LMS previously treated with an anthracycline.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) for chemotherapy agents, which is 5 half-lives before joining the study. If you are currently receiving chemotherapy, immunotherapy, or radiation therapy, you will need to stop these treatments before participating.

Is ADI-PEG 20 generally safe for humans?

ADI-PEG 20 has been tested in early-phase clinical trials for various cancers, showing tolerable side effects and some antitumor activity. However, more extensive trials are needed to fully understand its safety profile. ^{1 2 3 4 5}

What makes ADI-PEG 20 unique for treating leiomyosarcoma?

ADI-PEG 20 is unique because it targets the metabolism of cancer cells by depleting arginine, an amino acid that some tumors rely on for growth, which is different from traditional chemotherapy drugs that directly attack cancer cells. ^{6 7 8 9 10}

Research Team

John S Bomalaski

Principal Investigator

Polaris Group

Eligibility Criteria

This trial is for adults over 18 with advanced or metastatic Leiomyosarcoma (LMS), a type of soft tissue sarcoma, previously treated with an anthracycline. Participants must have measurable disease and good performance status, meaning they can carry out daily activities without significant limitations. They should not have had more than two systemic treatments but may have received Gemcitabine (Gem) or Docetaxel (Doc) over a year ago.

Inclusion Criteria

My soft tissue sarcoma is confirmed to be grade 2 or 3 and treatable with specific chemotherapy.

My cancer is identified as either uterine or non-uterine LMS.

I was treated with Gemcitabine or Docetaxel over a year ago.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ADI-PEG 20 or placebo plus Gemcitabine and Docetaxel in 21-day cycles

Up to 104 weeks

Weekly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ADI PEG20 (Enzyme Depletion)
• Placebo (Other)

Trial Overview The study is testing the effectiveness and safety of ADI-PEG 20 combined with chemotherapy drugs Gemcitabine and Docetaxel versus placebo plus these chemotherapies in patients with LMS who've already undergone some treatment. The goal is to see if ADI-PEG 20 can improve outcomes for these patients.

Participant Groups

Group I: ADIGemDoc Experimental Treatment 1 Intervention

ADI-PEG 20: 36 mg/m2 on Day -7 of Cycle 1, and Days 1, 8, and 15 of each 21-day cycle Gemcitabine: 600 mg/m2 on days 1 and 8 of each 21-day cycle Docetaxel: 60 mg/m2 on day 8 of each 21-day cycle

Group II: PBOGemDoc Placebo Group 1 Intervention

Placebo: matched PBO on Day -7 of Cycle 1, and Days 1, 8, and 15 of each 21-day cycle Gemcitabine: 900 mg/m2 on days 1 and 8 of each 21-day cycle Docetaxel: 75 mg/m2 on day 8 of each 21-day cycle

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Wake Forest Baptist (Atrium Health) Salem, NC

UHN - Princess Margaret Cancer Center (Ontario) Toronto, Canada

Northwestern Chicago, IL

Ohio State University Wexner Medical Center/ The James Cancer Hospital and Solove Research Institute Columbus, OH

More Trial Locations

Who Is Running the Clinical Trial?

Polaris Group

Lead Sponsor

Trials

25

Recruited

3,400+

Headquarters

Cayman Islands

Known For

Anti-Cancer Therapies

Top Products

ADI-PEG 20

Findings from Research

ADI-PEG 20, a pegylated enzyme that depletes arginine, was found to be well tolerated when combined with standard chemotherapy (gemcitabine and nab-paclitaxel) in patients with metastatic pancreatic cancer, with a recommended phase 2 dose of 36 mg/m2 weekly.

The treatment showed promising efficacy, with an overall response rate of 45.5% and a median overall survival time of 11.3 months among patients receiving the recommended dose, indicating potential benefits for both previously treated and untreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1/1B trial of ADI-PEG 20 plus nab-paclitaxel and gemcitabine in patients with advanced pancreatic adenocarcinoma. Lowery, MA., Yu, KH., Kelsen, DP., et al.[2022]

In a phase 1b study involving 25 patients, the combination of pegylated arginine deiminase (ADI-PEG 20) and pembrolizumab was found to be safe, although there was a higher-than-expected incidence of Grade 3/4 neutropenia in 40% of patients.

Treatment with ADI-PEG 20 led to increased T cell infiltration in tumors, which may enhance the effectiveness of pembrolizumab, with partial responses observed in 24% of heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1b study of pegylated arginine deiminase (ADI-PEG 20) plus Pembrolizumab in advanced solid cancers. Chang, KY., Chiang, NJ., Wu, SY., et al.[2021]

In a phase I study involving 18 patients with advanced solid tumors, the combination of pegylated arginine deiminase (ADI-PEG 20) and docetaxel showed manageable toxicity, with only one instance of dose-limiting toxicity and common hematologic side effects like leukopenia.

The treatment demonstrated promising clinical activity, with four partial responses and seven patients achieving stable disease, leading to further studies planned for specific cancer types at a recommended phase II dose of 36 mg/m².

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of Arginine Deprivation Therapy with ADI-PEG 20 Plus Docetaxel in Patients with Advanced Malignant Solid Tumors. Tomlinson, BK., Thomson, JA., Bomalaski, JS., et al.[2022]

In patients with ASS1-deficient malignant pleural mesothelioma (MPM) undergoing treatment with pegylated arginine deiminase (ADI-PEG20), increased macrophage infiltration was found to promote the survival of cancer cells, indicating a resistance mechanism against the therapy.

The study identified a CXCR2-dependent chemotactic signature and the role of IL-1α in macrophages, which contributes to the production of argininosuccinate that supports MPM cell viability, suggesting that targeting this macrophage-mediated resistance could enhance the effectiveness of arginine deprivation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A role for macrophages under cytokine control in mediating resistance to ADI-PEG20 (pegargiminase) in ASS1-deficient mesothelioma. Phillips, MM., Pavlyk, I., Allen, M., et al.[2023]

ADI-PEG20 is an innovative anticancer enzyme that effectively depletes arginine, which is crucial for certain tumors like malignant melanoma and hepatocellular carcinoma that cannot produce it themselves.

Early Phase I - II trials have demonstrated that ADI-PEG20 has antitumor activity and manageable side effects, but further large-scale Phase II and randomized Phase III trials are necessary to fully assess its efficacy in treating these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated arginine deiminase: a novel anticancer enzyme agent. Feun, L., Savaraj, N.[2019]

In a phase II study involving 34 patients with unresectable leiomyosarcoma (LMS), the combination of gemcitabine and docetaxel showed a high overall response rate of 53%, indicating significant efficacy in treating this challenging cancer, especially in patients who had previously received doxorubicin.

The treatment was generally well-tolerated, with manageable hematologic toxicities, such as neutropenia and thrombocytopenia, but rare instances of severe complications like neutropenic fever, suggesting a favorable safety profile for this chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. Hensley, ML., Maki, R., Venkatraman, E., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

A phase 1/1B trial of ADI-PEG 20 plus nab-paclitaxel and gemcitabine in patients with advanced pancreatic adenocarcinoma. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Phase 1b study of pegylated arginine deiminase (ADI-PEG 20) plus Pembrolizumab in advanced solid cancers. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Phase I Trial of Arginine Deprivation Therapy with ADI-PEG 20 Plus Docetaxel in Patients with Advanced Malignant Solid Tumors. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

A role for macrophages under cytokine control in mediating resistance to ADI-PEG20 (pegargiminase) in ASS1-deficient mesothelioma. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Pegylated arginine deiminase: a novel anticancer enzyme agent. [2019]

6. Netherlands pubmed.ncbi.nlm.nih.gov

A patient-derived orthotopic xenograft (PDOX) nude-mouse model precisely identifies effective and ineffective therapies for recurrent leiomyosarcoma. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Adjuvant gemcitabine-docetaxel chemotherapy for stage I uterine leiomyosarcoma: Trends and survival outcomes. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Fixed-dose rate gemcitabine plus docetaxel as first-line therapy for metastatic uterine leiomyosarcoma: a Gynecologic Oncology Group phase II trial. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Prolonged disease stability with trabectedin in a heavily pretreated elderly patient with metastatic leiomyosarcoma of the thigh and renal failure: a case report and review of the literature. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. [2022]