Ipatasertib + Megestrol Acetate for Endometrial Cancer

Recruiting at 151 trial locations

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: National Cancer Institute (NCI)

Must not be taking: AKT inhibitors, Strong CYP3A inhibitors

Disqualifiers: Diabetes, Hypercholesterolemia, Liver disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing if combining two drugs, ipatasertib and megestrol acetate, is more effective than using megestrol acetate alone for treating women with endometrial cancer that has returned or spread. Ipatasertib blocks enzymes needed for cancer cell growth, while megestrol acetate reduces and blocks estrogen, which some cancer cells need to grow.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken strong CYP3A inhibitors or inducers within 14 days before joining. It's best to discuss your current medications with the trial team to ensure there are no interactions.

What data supports the effectiveness of the drug combination Ipatasertib and Megestrol Acetate for treating endometrial cancer?

Research shows that Megestrol Acetate, one of the drugs in the combination, has been effective in treating endometrial cancer by inhibiting the recurrence of certain types of endometrial lesions and increasing survival in patients with recurrent endometrial cancer. ^{1 2 3 4 5}

Is the combination of Ipatasertib and Megestrol Acetate safe for treating endometrial cancer?

Megestrol Acetate has been used safely in treating advanced breast cancer and endometrial cancer, with studies showing it is well tolerated and has a good safety profile. It is important to note that while these studies focus on Megestrol Acetate, specific safety data for the combination with Ipatasertib is not provided. ^{1 3 6 7 8}

How is the drug combination of Ipatasertib and Megestrol Acetate unique for treating endometrial cancer?

The combination of Ipatasertib and Megestrol Acetate is unique because Ipatasertib is a novel drug that targets specific pathways involved in cancer cell growth, potentially offering a new mechanism of action compared to traditional treatments like hormonal therapies or chemotherapy. ^{1 3 4 5 9}

Research Team

Michaela O. Grinsfelder

Principal Investigator

NRG Oncology

Eligibility Criteria

This trial is for adults with grade 1 or 2 recurrent or metastatic endometrioid endometrial cancer. Participants can have had any number of prior treatments but must not have received hormonal therapy within the last 6 months. They should be able to take oral medication, have no severe liver disease, uncontrolled diabetes, significant heart issues, active infections requiring IV antibiotics, and agree to use contraception if they can bear children.

Inclusion Criteria

Participants of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) during study therapy and for 28 days following the last dose of study therapy. Should a participant become pregnant or suspect pregnancy while participating in this study, they should inform their treating physician immediately

My heart function is classified as class 2B or better, despite my history of heart issues or treatments.

I have completed any hormonal cancer treatments at least 6 months ago.

Exclusion Criteria

I am not currently on IV antibiotics for an infection.

I have not been treated with AKT inhibitors before, but may have had PI3K or mTOR inhibitors.

I am not pregnant and not nursing, or I am willing to stop nursing.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Phase Ib Treatment

Patients receive megestrol acetate and ipatasertib orally once daily. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

Regular visits for CT/MRI and blood sample collection

Phase II Treatment

Patients are randomized to receive either megestrol acetate alone or in combination with ipatasertib. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

Regular visits for CT/MRI and blood sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs every 3 months for 2 years, then every 6 months for 3 years.

Up to 5 years

Follow-up visits every 3-6 months

Treatment Details

Interventions

• Ipatasertib (AKT Inhibitor)
• Megestrol Acetate (Hormone Therapy)

Trial Overview The trial is testing whether adding Ipatasertib to Megestrol Acetate improves treatment outcomes in patients with advanced endometrial cancer. Ipatasertib blocks enzymes that may help tumor cells grow while Megestrol Acetate lowers estrogen levels which some tumor cells need to grow. The study will determine the safety and optimal doses as well as compare effectiveness against using Megestrol alone.

Participant Groups

Group I: Phase Ib (megestrol acetate, ipatasertib) Experimental Treatment 5 Interventions

Patients receive megestrol acetate PO QD on days 1-28 and ipatasertib PO QD on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI during screening, on study, and during follow-up. Patients also undergo collection of blood samples throughout the trial.

Group II: Phase II (megestrol acetate, ipatasertib) Experimental Treatment 5 Interventions

Arm II: Patients receive megestrol acetate PO QD on days 1-28 and ipatasertib PO QD on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI during screening, on study, and during follow-up. Patients also undergo collection of blood samples throughout the trial.

Group III: Phase II (megestrol acetate) Active Control 4 Interventions

Arm I: Patients receive megestrol acetate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI during screening, on study, and during follow-up. Patients also undergo collection of blood samples throughout the trial.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Findings from Research

In a study of 28 patients with advanced or recurrent endometrial cancer, the combination of paclitaxel, carboplatin, and megestrol acetate resulted in a mean overall survival of 50.1 months and a mean progression-free interval of 40.2 months, indicating significant efficacy of this treatment regimen.

While myelosuppression was a common side effect, affecting 78% of patients with severe neutropenia, the toxicity was manageable, suggesting that the addition of hormonal therapy to chemotherapy may enhance survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy with paclitaxel, carboplatin and megestrol acetate for the management of advanced stage or recurrent carcinoma of the endometrium: a phase II study. Bevis, KS., Kilgore, LC., Alvarez, RD., et al.[2015]

Megestrol acetate has been shown to effectively inhibit the recurrence of endometrial hyperplasia and adenocarcinoma, which are conditions that can progress to invasive cancer if untreated.

In patients with inoperable endometrial adenocarcinoma, megestrol acetate not only treats the cancer but also increases survival rates in those with recurrent cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progestin therapy in lesions of the endometrium. Wentz, WB.[2013]

In a study of 26 young women with well-differentiated endometrioid carcinoma or atypical hyperplasia, 80.8% responded to treatment with megestrol acetate after hysteroscopic curettage, indicating its efficacy as a fertility-sparing option.

Despite the effectiveness, there was a notable recurrence rate of 23.1% after a median follow-up of 32 months, particularly among patients with infertility or PCOS, highlighting the need for careful patient selection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective study of fertility-sparing treatment with megestrol acetate following hysteroscopic curettage for well-differentiated endometrioid carcinoma and atypical hyperplasia in young women. Shan, BE., Ren, YL., Sun, JM., et al.[2013]

In a study of 66 patients with advanced endometrial cancer, the combination of megestrol and tamoxifen showed a similar response rate (19%) to megestrol alone (20%), indicating no significant clinical advantage of the combination therapy.

While megestrol alone had only mild to moderate side effects, the combination therapy resulted in more severe toxicities, including a life-threatening pulmonary embolism, suggesting that adding tamoxifen may increase risks without improving efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Megestrol and tamoxifen in patients with advanced endometrial cancer: an Eastern Cooperative Oncology Group Study (E4882). Pandya, KJ., Yeap, BY., Weiner, LM., et al.[2019]

In a study of 61 women with recurrent or advanced endometrial carcinoma, alternating treatment with megestrol acetate and tamoxifen resulted in a 27% overall response rate, with some patients experiencing responses lasting over 20 months.

The treatment was associated with manageable toxicity, including two cases of severe thromboembolic events, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of alternating courses of megestrol acetate and tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study. Fiorica, JV., Brunetto, VL., Hanjani, P., et al.[2019]

In a study of 101 patients with advanced breast cancer, megestrol acetate showed a 26% improvement rate, indicating its potential efficacy as a treatment option.

The drug was well tolerated with no observed toxicity or endocrine effects, making it a favorable choice for initial hormonal therapy in postmenopausal patients with disseminated breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Further clinical studies with megestrol acetate in advanced breast cancer. Ansfield, FJ., Davis, HL., Ramirez, G., et al.[2019]

Megestrol acetate is an effective hormonal therapy for advanced breast cancer, showing an overall response rate of 30%, comparable to tamoxifen, and has a strong safety profile.

It may be particularly beneficial for patients experiencing cancer cachexia due to its associated weight gain, and it could serve as a viable treatment option for those whose disease progresses during tamoxifen therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An overview of megestrol acetate for the treatment of advanced breast cancer. Sedlacek, SM.[2018]

Hormonal manipulation has been a long-standing treatment for advanced breast cancer, with various methods like surgical ablation and high doses of hormones showing significant tumor regression in sensitive patients.

Megace (megestrol acetate) is highlighted as a therapy option that aims to achieve effective responses while minimizing toxicity, reflecting the current trend in selecting treatments for advanced breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Megestrol acetate in breast cancer--a panel discussion. McGuire, WL., Johnson, PA., Muss, HB., et al.[2019]

A 71-year-old woman with recurrent, metastatic endometrial cancer experienced significant clinical stability and a good quality of life for approximately 57 months while treated with a combination of tamoxifen and megestrol acetate, highlighting the potential effectiveness of this endocrine therapy.

This case suggests that combination endocrine therapy can be a viable treatment option for patients with recurrent, ER/PR-positive endometrial cancer, offering substantial long-term benefits with minimal side effects, even after multiple prior treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case report: prolonged durable clinical benefit and low toxicity from combination endocrine therapy in a patient with recurrent endometrial carcinoma. Cheng, JM., Gaillard, S., Beavis, AL., et al.[2023]

References

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

Combination therapy with paclitaxel, carboplatin and megestrol acetate for the management of advanced stage or recurrent carcinoma of the endometrium: a phase II study. [2015]

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

Progestin therapy in lesions of the endometrium. [2013]

3. Germany pubmed.ncbi.nlm.nih.gov

A prospective study of fertility-sparing treatment with megestrol acetate following hysteroscopic curettage for well-differentiated endometrioid carcinoma and atypical hyperplasia in young women. [2013]

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

Megestrol and tamoxifen in patients with advanced endometrial cancer: an Eastern Cooperative Oncology Group Study (E4882). [2019]

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

Phase II trial of alternating courses of megestrol acetate and tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study. [2019]

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

Further clinical studies with megestrol acetate in advanced breast cancer. [2019]

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

An overview of megestrol acetate for the treatment of advanced breast cancer. [2018]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Megestrol acetate in breast cancer--a panel discussion. [2019]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Case report: prolonged durable clinical benefit and low toxicity from combination endocrine therapy in a patient with recurrent endometrial carcinoma. [2023]