What side effects are associated with this type of intervention?

Common treatments for uterine cancer, such as enzyme inhibitors like Ipatasertib and hormonal agents like Megestrol Acetate, have distinct side effect profiles. Enzyme inhibitors can cause diarrhea, nausea, fatigue, and rash. Hormonal treatments can lead to weight gain, fluid retention, thromboembolic events, and mood changes. Combining these treatments may result in a combination of these side effects, requiring careful monitoring and management.

What prior FDA approvals exist?

FDA-approved treatments for uterine cancer that are similar to the investigational agents ipatasertib and megestrol acetate include mTOR inhibitors like everolimus, which targets a related pathway involved in cell growth and survival. Additionally, hormonal therapies such as progestins and aromatase inhibitors (e.g., letrozole) have been used, although their efficacy varies. These treatments aim to reduce estrogen levels or block its effects, similar to megestrol acetate.

What other types of research exist?

Promising novel alternatives for uterine cancer treatment in 2024 include: 1) mTOR inhibitors like Temsirolimus, which have shown some promise in clinical trials, especially when combined with other agents like bevacizumab. 2) The combination of Everolimus (another mTOR inhibitor) with Letrozole, which has demonstrated a clinical benefit rate in phase II studies. These alternatives target pathways involved in cellular growth and survival, similar to Ipatasertib and Megestrol Acetate.

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AKT Inhibitor

Ipatasertib + Megestrol Acetate for Endometrial Cancer

Phase 1 & 2

Recruiting

Led By Michaela O Grinsfelder

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include digestive issues due to both drugs' impact on hormone levels and gastrointestinal absorption; increased blood sugar levels; potential liver problems; fatigue from immune system impacts; and risks associated with taking pills that might affect other medications.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of AEs (Phase II)

Incidence of adverse events (AEs) (Phase Ib)

Maximum tolerated dose for phase II (Phase Ib)

+1 more

Secondary study objectives

Biomarkers (Phase II)

Objective response rate (ORR) (Phase II)

Pharmacokinetics of ipatasertib + megestrol acetate (Phase Ib)

Other study objectives

pS6/total S6 and pPRAS40/total PRAS40 expression (Phase II)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Phase Ib (megestrol acetate, ipatasertib)Experimental Treatment5 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 Treatment5 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 Control4 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biospecimen Collection

2004

Completed Phase 3

~2020

Computed Tomography

2017

Completed Phase 2

~2740

Ipatasertib

2017

Completed Phase 3

~3630

Magnetic Resonance Imaging

2017

Completed Phase 3

~1160

Megestrol Acetate

2007

Completed Phase 3

~540

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for uterine cancer often involve mechanisms such as enzyme inhibition and estrogen reduction/blockade. Enzyme inhibitors like Ipatasertib target specific enzymes involved in cell growth and survival pathways, potentially stopping tumor growth and inducing cancer cell death. Estrogen reduction and blockade, as seen with Megestrol Acetate, lower estrogen levels and prevent the hormone from stimulating cancer cell growth. These mechanisms are crucial for uterine cancer patients because they directly interfere with the biological processes that allow cancer cells to proliferate, offering targeted and effective treatment options.

A Phase 2, Randomized, Open-Label Study of Irosustat Versus Megestrol Acetate in Advanced Endometrial Cancer.[Impact of the cellular estradiol response on the therapeutic inhibition of growth factor signaling].