190 Participants Needed

Olaparib + Temozolomide for Uterine Leiomyosarcoma

Recruiting at 151 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

This phase II/III trial compares the effect of the combination treatment with olaparib and temozolomide to trabectedin or pazopanib (two of the most common chemotherapy drugs used as usual approach) in patients with uterine leiomyosarcoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) after initial chemotherapy has stopped working. The usual approach is defined as care most people get for advanced uterine leiomyosarcoma. Olaparib is a PARP inhibitor. PARP is a protein that helps repair damaged deoxyribonucleic acid (DNA). Blocking PARP may prevent tumor cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Temozolomide is in a class of medications called alkylating agents. It works by slowing or stopping the growth of tumor cells in the body. The combination of olaparib and temozolomide may work better than the usual treatment in shrinking or stabilizing advanced uterine leiomyosarcoma after initial chemotherapy has stopped working.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that are strong or moderate CYP3A inhibitors or inducers. There is a required washout period (time without taking these medications) of 2 weeks for inhibitors and up to 5 weeks for some inducers before starting the study treatment.

What data supports the effectiveness of the drug combination Olaparib and Temozolomide for treating uterine leiomyosarcoma?

Research shows that the combination of Olaparib and Temozolomide was highly effective in preclinical studies for inhibiting tumor growth in uterine leiomyosarcoma, a type of aggressive cancer. Additionally, Olaparib has shown promising results in treating ovarian cancer, especially in patients with certain genetic mutations, suggesting its potential effectiveness in other cancers with similar characteristics.12345

Is Olaparib safe for use in humans?

Olaparib (Lynparza) has been tested in various clinical trials for ovarian cancer and is approved for use in patients with certain genetic mutations. It has been evaluated for safety in these trials, indicating it is generally safe for human use in the context of ovarian cancer treatment.23456

What makes the drug combination of Olaparib and Temozolomide unique for treating uterine leiomyosarcoma?

The combination of Olaparib and Temozolomide is unique because it targets cancer cells in a novel way by combining a PARP inhibitor (Olaparib) with a chemotherapy agent (Temozolomide), potentially enhancing the effectiveness of treatment for uterine leiomyosarcoma, a condition with limited standard treatment options.7891011

Research Team

BV

Brian Van Tine

Principal Investigator

Alliance for Clinical Trials in Oncology

Eligibility Criteria

This trial is for adults with advanced uterine leiomyosarcoma that has worsened after at least two prior treatments, including an anthracycline. Participants must have measurable disease, be in relatively good health (ECOG <=2), and women must test negative for pregnancy. Those with significant treatment-related side effects or who haven't recovered from previous therapies are excluded.

Inclusion Criteria

I can speak and/or read English and Spanish.
I can take care of myself but might not be able to do heavy physical work.
I don't have uncontrolled heart rhythm problems or recent heart attacks.
See 26 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either olaparib plus temozolomide or investigator's choice of trabectedin or pazopanib. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Up to 5 years
Regular visits for CT/MRI scans and blood sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs every 6 weeks until disease progression, then every 3 months for the first 2 years, and every 6 months thereafter until 5 years post-randomization or death.

Up to 5 years

Treatment Details

Interventions

  • Olaparib
  • Temozolomide
Trial OverviewThe study compares a new combination of drugs (Olaparib and Temozolomide) against standard chemotherapy options (Trabectedin or Pazopanib) for advanced uterine leiomyosarcoma post-initial chemo failure. Olaparib may prevent tumor DNA repair, while Temozolomide aims to slow tumor growth.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm 1 (olaparib, temozolomide)Experimental Treatment8 Interventions
Patients receive temozolomide PO QD on days 1-7 of each cycle and olaparib PO BID on days 1-7 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and/or bone scans throughout the trial. Patients also undergo collection of blood samples throughout the trial.
Group II: Arm 2 (trabectedin, pazopanib)Active Control8 Interventions
Patients receive trabectedin IV continuously over 24 hours on day 1 of each cycle or pazopanib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and/or bone scans throughout the trial. Patients also undergo TTE or MUGA on study and as clinically indicated, as well as collection of blood samples throughout the trial.

Olaparib is already approved in European Union, United States for the following indications:

🇪🇺
Approved in European Union as Lynparza for:
  • Breast cancer
  • Ovarian cancer
  • Fallopian tube cancer
  • Peritoneal cancer
  • Pancreatic cancer
  • Prostate cancer
  • Endometrial cancer
🇺🇸
Approved in United States as Lynparza for:
  • Ovarian, fallopian tube, and primary peritoneal cancer
  • Breast cancer
  • Prostate cancer
  • Pancreatic cancer

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Findings from Research

In a phase II study involving 22 patients with advanced uterine leiomyosarcoma (uLMS), the combination of olaparib and temozolomide showed a promising objective response rate of 27%, indicating potential efficacy in this aggressive cancer type.
Patients with homologous recombination-deficient tumors experienced significantly longer progression-free survival (11.2 months) compared to those with proficient tumors (5.4 months), suggesting that genetic profiling could help tailor treatment strategies.
Phase II Study of Olaparib and Temozolomide for Advanced Uterine Leiomyosarcoma (NCI Protocol 10250).Ingham, M., Allred, JB., Chen, L., et al.[2023]
Olaparib is an effective oral treatment for patients with BRCA mutation-positive ovarian cancer, approved for maintenance therapy after platinum-based chemotherapy, showing good tolerability with common side effects like nausea, fatigue, and anemia being mild to moderate.
Long-term monitoring is recommended due to a low risk of serious hematological complications, such as anemia and myelodysplastic syndrome, ensuring patient safety during treatment.
Safety evaluation of olaparib for treating ovarian cancer.Lheureux, S., Bowering, V., Karakasis, K., et al.[2015]
Olaparib, a PARP inhibitor, showed a 36% objective response rate in women with relapsed ovarian cancer and a germline BRCA1/2 mutation, even after they had undergone multiple lines of chemotherapy, indicating its efficacy in this challenging patient population.
The median duration of response to olaparib was 7.4 months, and the safety profile was consistent across patients who had received three or more lines of prior chemotherapy, with similar rates of serious adverse events.
Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety.Matulonis, UA., Penson, RT., Domchek, SM., et al.[2022]

References

Phase II Study of Olaparib and Temozolomide for Advanced Uterine Leiomyosarcoma (NCI Protocol 10250). [2023]
Safety evaluation of olaparib for treating ovarian cancer. [2015]
Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. [2022]
Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. [2020]
Olaparib: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian cancer. [2016]
Olaparib: first global approval. [2020]
Vorapaxar and optimal aspirin dose: The FDA outlook. [2016]
Investigation of the effects of heparin and low molecular weight heparin on E-cadherin and laminin expression in rat pregnancy by immunohistochemistry. [2023]
Talimogene Laherparepvec: An Oncolytic Virus Therapy for Melanoma. [2018]
Low molecular weight heparins for venous thromboembolism. [2019]
11.United Statespubmed.ncbi.nlm.nih.gov
Perioperative Recovery and Narcotic Use in Laparoscopic versus Robotic Surgery for Endometrial Cancer. [2021]