159 Participants Needed

mTOR/AKT Inhibitors for Endometrial and Ovarian Cancer

No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications and substances are prohibited within specific wash-out periods, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug AZD2014, AZD5363, Olaparib, Lynparza for endometrial and ovarian cancer?

Research shows that the mTOR/AKT pathway, which these drugs target, is often overactive in endometrial and ovarian cancers. Early studies have shown promising results with mTOR inhibitors in these cancers, suggesting they may help slow tumor growth and improve outcomes.12345

Is olaparib safe for humans?

Olaparib has been studied in patients with advanced ovarian cancer, and while it offers benefits, it can also cause side effects. Common side effects include blood-related issues and other non-blood-related problems, but the specific details on safety are not fully detailed in the available studies.678910

What makes the drug AZD2014, AZD5363, and Olaparib unique for endometrial and ovarian cancer?

This drug combination targets the PI3K/AKT/mTOR pathway, which is often overactive in endometrial and ovarian cancers, offering a novel approach by potentially reducing tumor growth and resistance to other treatments. Unlike standard therapies, this combination includes mTOR inhibitors and Olaparib, a PARP inhibitor, which may enhance effectiveness in these cancers.134511

What is the purpose of this trial?

This phase Ib/II trial studies the side effects and best dose of olaparib and vistusertib (AZD2014) or olaparib and capivasertib (AZD5363) when given together in treating patients with endometrial, triple negative breast cancer, ovarian, primary peritoneal, or fallopian tube cancer that has come back (recurrent). Olaparib, vistusertib, and capivasertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Research Team

MD Anderson Cancer Center

Shannon Westin, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients with recurrent endometrial, ovarian, peritoneal, fallopian tube cancer or triple negative breast cancer. Participants must have a life expectancy over 4 months and be able to take oral meds. They should agree to use contraception and have specific blood levels within normal ranges. Those with other recent cancers or certain health conditions can't join.

Inclusion Criteria

You are expected to live for more than 4 months.
Understanding and willingness to sign an informed consent
You need to provide samples from when you were first diagnosed or when the cancer came back.
See 10 more

Exclusion Criteria

I am not taking any experimental drugs or additional cancer treatments.
Known hypersensitivity to study drugs or similar drugs
Unsuitability and non-compliance with study procedures
See 16 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olaparib and either vistusertib or capivasertib in various dosing schedules over 28-day cycles

28 days per cycle
Continuous monitoring with regular visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks
1 visit (in-person)

Long-term follow-up

Participants are monitored for progression-free survival and response duration

6 months

Treatment Details

Interventions

  • AZD2014
  • AZD5363
  • Olaparib
Trial Overview The study tests the combination of olaparib with either vistusertib (AZD2014) or capivasertib (AZD5363) on tumor growth in selected cancers. It aims to find the safest doses and observe how well these drug combinations work against recurrent cancers by blocking enzymes that promote cell growth.
Participant Groups
3Treatment groups
Experimental Treatment
Group I: Arm III (olaparib, capivasertib)Experimental Treatment3 Interventions
INTERMITTENT AZD5363 DOSING: Patients receive olaparib PO BID on days 1-28 (on days 5-28 of course 1 and alone on days -3 to -1 of week -1) and capivasertib PO BID for 4 days on and 3 days off (alone on days 1-4 of week 1).
Group II: Arm II (olaparib, vistusertib)Experimental Treatment3 Interventions
INTERMITTENT AZD2014 DOSING: Patients receive olaparib PO BID on days 1-28 (days 3-28 on course 1 and alone on days -5 to -3 of week -1) and vistusertib 4 PO BID for 2 days on and 5 days off (alone on days 1-2 of week 1).
Group III: Arm I (olaparib, vistusertib)Experimental Treatment4 Interventions
CONTINUOUS AZD2014 DOSING: Patients receive olaparib PO BID on days 1-28 (days 5-28 of course 1 and alone on days -3 to -1 of week -1) and vistusertib PO BID on days 1-28 (alone on days 1-4 of week 1).

Find a Clinic Near You

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials
3,107
Recruited
1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Findings from Research

In a study involving 44 women with platinum-refractory ovarian cancer or advanced endometrial carcinoma, the mTOR inhibitor temsirolimus was found to be well tolerated with mild toxicity, but it did not meet the predefined efficacy criteria for progression-free survival.
Despite the overall lack of efficacy, some patients experienced long-lasting disease stabilization, indicating that temsirolimus may still have potential benefits for a subset of patients.
Temsirolimus in women with platinum-refractory/resistant ovarian cancer or advanced/recurrent endometrial carcinoma. A phase II study of the AGO-study group (AGO-GYN8).Emons, G., Kurzeder, C., Schmalfeldt, B., et al.[2016]
In the phase III SOLO1 trial, maintenance treatment with olaparib significantly improved progression-free survival in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation, with 260 patients receiving olaparib compared to 131 on placebo.
The most common adverse events associated with olaparib, such as anemia and nausea, occurred early (within 3 months) but were manageable, with only a small number of patients needing to discontinue treatment, indicating a predictable safety profile.
Tolerability of maintenance olaparib in newly diagnosed patients with advanced ovarian cancer and a BRCA mutation in the randomized phase III SOLO1 trial.Colombo, N., Moore, K., Scambia, G., et al.[2022]
Olaparib (OLA) monotherapy showed a similar overall objective response rate (ORR) compared to chemotherapy (CT) in patients with relapsed ovarian cancer, with ORR of 24.3% for OLA and 28.3% for CT, indicating comparable efficacy.
In patients with platinum-resistant ovarian cancer (PROC) who had received more than four prior lines of treatment, OLA demonstrated a higher ORR of 22.9% compared to 0% for CT, suggesting that OLA may be more effective in heavily pretreated cases.
Randomized CLIO/BGOG-ov10 trial of olaparib monotherapy versus physician's choice chemotherapy in relapsed ovarian cancer.Vanderstichele, A., Loverix, L., Busschaert, P., et al.[2022]

References

Exploiting the therapeutic potential of the PI3K-AKT-mTOR pathway in enriched populations of gynecologic malignancies. [2021]
Biologic rationale and clinical activity of mTOR inhibitors in gynecological cancer. [2021]
A randomized phase II trial of everolimus and letrozole or hormonal therapy in women with advanced, persistent or recurrent endometrial carcinoma: A GOG Foundation study. [2022]
The rationale for mTOR inhibition in epithelial ovarian cancer. [2021]
Temsirolimus in women with platinum-refractory/resistant ovarian cancer or advanced/recurrent endometrial carcinoma. A phase II study of the AGO-study group (AGO-GYN8). [2016]
Tolerability of maintenance olaparib in newly diagnosed patients with advanced ovarian cancer and a BRCA mutation in the randomized phase III SOLO1 trial. [2022]
Randomized CLIO/BGOG-ov10 trial of olaparib monotherapy versus physician's choice chemotherapy in relapsed ovarian cancer. [2022]
Real-world clinical outcomes of olaparib therapy in Chinese patients with advanced serous ovarian cancer treated in Macau. [2021]
Efficacy of Maintenance Olaparib for Patients With Newly Diagnosed Advanced Ovarian Cancer With a BRCA Mutation: Subgroup Analysis Findings From the SOLO1 Trial. [2021]
Olaparib for the treatment of BRCA-mutated advanced ovarian cancer. [2019]
11.United Statespubmed.ncbi.nlm.nih.gov
Dual mTORC1/2 inhibition in a preclinical xenograft tumor model of endometrial cancer. [2021]
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