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Active, not recruiting Phase 1/2

Testing the Addition of the AKT Inhibitor, Ipatasertib, to Treatment With the Hormonal Agent Megestrol Acetate for Recurrent or Metastatic Endometrial Cancers

NCT05538897 · tracked via the Priya Life Science Mexico tracker
Phase
Phase 1/2
Started
2023-03-31
Last updated
2026-10-01

Condition(s) studied

FIGO Grade 1 Endometrial Endometrioid AdenocarcinomaFIGO Grade 2 Endometrial Endometrioid AdenocarcinomaMetastatic Endometrial Endometrioid AdenocarcinomaRecurrent Endometrial Endometrioid Adenocarcinoma

Investigational drug(s) / intervention(s)

Biospecimen CollectionComputed TomographyIpatasertib →Magnetic Resonance ImagingMegestrol Acetate →

Biospecimen Collection: Undergo blood sample collection

Computed Tomography: Undergo CT scan

Ipatasertib: Given PO

Magnetic Resonance Imaging: Undergo MRI

Megestrol Acetate: Given PO

Study summary

This phase Ib/II trial tests the safety, side effects, best dose, and effectiveness of the combination of ipatasertib with megestrol acetate to megestrol acetate alone in patients with endometrial cancer that has come back (recurrent) or has spread to other places in the body (metastatic). Ipatasertib may stop the growth of tumor cells and may kill them by blocking some of the enzymes needed for cell growth. Megestrol acetate lowers the amount of estrogen and also blocks the use of estrogen made by the body. This may help stop the growth of tumor cells that need estrogen to grow. The combination of ipatasertib and megestrol acetate may be more effective in treating endometrial cancer than megestrol acetate alone.

Eligibility

Sex
FEMALE
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria: * Patients must have grade 1 or 2 recurrent or metastatic endometrioid endometrial cancer * Patients must have measurable disease according to RECIST version (v)1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be \>= 10 mm when measured by CT or MRI. Lymph nodes must be \>= 15 mm in short axis when measured by CT or MRI. Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation * Patients may have received unlimited prior lines of therapy. If patient received prior hormonal therapy (e.g., megestrol acetate, medroxyprogesterone acetate, aromatase inhibitor, tamoxifen, fulvestrant) it must have completed at least 6 months prior to registration * Age \>= 18 * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2 * Platelets \>= 100,000/mcl within 14 days prior to registration * Absolute neutrophil count (ANC) \>= 1,500/mcl within 14 days prior to registration * Hemoglobin \>= 9 g/dL within 14 days prior to registration * Glomerular filtration rate (GFR) \>= 60 mL/min/1.73m\^2 measured using Cockcroft-Gault equation or the estimated glomerular filtration rate from the Modification of Diet in Renal Disease Study within 14 days prior to registration * Total bilirubin =\< 1.5 x the upper limit of normal (ULN) within 14 days prior to registration * Patients with known Gilbert syndrome who have bilirubin =\< 3 x ULN may be enrolled * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN within 14 days prior to registration * Albumin \>= 3 g/dL within 14 days prior to registration * Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better * The effects of ipatasertib on the developing human fetus are unknown. For this reason and because AKT inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, 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 * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial * For patients with known human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV) infection: * HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial * Patients with evidence of chronic hepatitis B virus (HBV) infection must have an undetectable HBV viral load on suppressive therapy, if indicated * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load * Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression * Patients must be able to swallow and retain oral medications and not have gastrointestinal illnesses that would preclude absorption of megestrol acetate or ipatasertib as judged by the treating physician * The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information Exclusion Criteria: * Patients who have had prior treatment with an AKT inhibitor (Prior treatment with PI3K or mTOR inhibitors is allowed) * Patients who have received treatment with strong CYP3A inhibitors or inducers within 14 days or 5 drug-elimination half-lives, whichever is longer, prior to study registration * Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product * Patients with diabetes either requiring insulin therapy or with a baseline fasting glucose \> 160 mg/dL and/or high glycosylated hemoglobin A1c (HbA1c) (\> 8), suggesting poorly controlled diabetes. Fasting is defined as abstaining from food and drink (with the exception of water) for at least 8 hours * Patients who require chronic corticosteroid therapy of \> 10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids or immunosuppressant agents for a chronic disease * Patients with grade 2 or greater uncontrolled or untreated hypercholesterolemia (\> 300 mg/dL) or hypertriglyceridemia (\> 300 mg/dL) * Patients with a history of known or active inflammatory bowel disease (e.g., Crohn disease and ulcerative colitis) or active bowel inflammation (e.g., diverticulitis) * Patients with a history of or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion (including complete left bundle branch block, second- or third-degree heart block, or evidence of prior myocardial infarction) * Patients with known clinically significant history of liver disease consistent with Child-Pugh class B or C, including active viral or other hepatitis, current drug or alcohol abuse, or cirrhosis * Patients with lung disease: Grade 2 or greater pneumonitis, grade 2 or greater interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, aspergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia) within the past 6 months * No active infection requiring parenteral antibiotics * Women who are pregnant or unwilling to discontinue nursing

Primary outcome measure(s)

  • Incidence of adverse events (AEs) (Phase Ib) — Up to 5 years
    To determine frequency and severity of adverse events for all dose combinations of megestrol acetate plus ipatasertib. Descriptive statistics will be used to summarize AEs. These analyses will focus on individuals who initiated their assigned treatment and will summarize maximum grade of AEs occurring during treatment classified by Common Toxicity Criteria (CTC) category. The primary summary of AEs will present counts and percentages, regardless of whether the AE was attributed to any of the study agents.
  • Maximum tolerated dose for phase II (Phase Ib) — Up to 5 years
    Descriptive statistics will be used to summarize AEs. These analyses will focus on individuals who initiated their assigned treatment and will summarize maximum grade of AEs occurring during treatment classified by CTC category. The primary summary of AEs will present counts and percentages, regardless of whether the AE was attributed to any of the study agents.
  • Progression free survival (PFS) (Phase II) — From study entry to time of progression or death, whichever occurs first, or date of last contact if neither progression nor death has occurred, assessed up to 5 years
    Compare PFS of the combination of ipatasertib with megestrol acetate to megestrol acetate alone among women with recurrent/metastatic endometrioid adenocarcinoma of the endometrium. A product-limit method will be used to estimate the cumulative distribution of PFS duration for each of the study treatments used in this population.
  • Incidence of AEs (Phase II) — Up to 5 years
    Summarize the toxicity/adverse events of the combination of ipatasertib with megestrol acetate and megestrol acetate alone. Adverse events will be categorized using Common Terminology Criteria for Adverse Events version 5.0.

Trial sites (152)

FacilityCityRegionStatus
Banner University Medical Center - Tucson Tucson Arizona
University of Arizona Cancer Center-North Campus Tucson Arizona
Highlands Oncology Group - Fayetteville Fayetteville Arkansas
Highlands Oncology Group - Rogers Rogers Arkansas
Highlands Oncology Group Springdale Arkansas
University of California Davis Comprehensive Cancer Center Sacramento California
UCHealth University of Colorado Hospital Aurora Colorado
UF Health Cancer Institute - Gainesville Gainesville Florida
Sarasota Memorial Hospital-Venice N. Venice Florida
Florida Cancer Specialists - Sarasota Downtown Sarasota Florida
FPG - Surgical Oncology Clinics Gynecologic Oncology Surgery Sarasota Florida
Sarasota Memorial Hospital Sarasota Florida
Florida Cancer Specialists - Venice Pinebrook Venice Florida
Augusta University Medical Center Augusta Georgia
Saint Alphonsus Cancer Care Center-Boise Boise Idaho
Saint Luke's Cancer Institute - Boise Boise Idaho
Saint Alphonsus Cancer Care Center-Caldwell Caldwell Idaho
Kootenai Health - Coeur d'Alene Coeur d'Alene Idaho
Saint Luke's Cancer Institute - Fruitland Fruitland Idaho
Saint Luke's Cancer Institute - Meridian Meridian Idaho
Saint Alphonsus Cancer Care Center-Nampa Nampa Idaho
Saint Luke's Cancer Institute - Nampa Nampa Idaho
Kootenai Clinic Cancer Services - Post Falls Post Falls Idaho
Kootenai Clinic Cancer Services - Sandpoint Sandpoint Idaho
Northwestern University Chicago Illinois
University of Illinois Chicago Illinois
Carle at The Riverfront Danville Illinois
Cancer Care Specialists of Illinois - Decatur Decatur Illinois
Decatur Memorial Hospital Decatur Illinois
Northwestern Medicine Cancer Center Kishwaukee DeKalb Illinois
Carle Physician Group-Effingham Effingham Illinois
Crossroads Cancer Center Effingham Illinois
Northwestern Medicine Cancer Center Delnor Geneva Illinois
Northwestern Medicine Grayslake Outpatient Center Grayslake Illinois
Northwestern Medicine Lake Forest Hospital Lake Forest Illinois
Carle Physician Group-Mattoon/Charleston Mattoon Illinois
Cancer Care Center of O'Fallon O'Fallon Illinois
Northwestern Medicine Orland Park Orland Park Illinois
Southern Illinois University School of Medicine Springfield Illinois
Springfield Clinic Springfield Illinois

+ 112 more sites — see the full list on the official registry below.

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05538897 on ClinicalTrials.gov ↗ ← All trials in Mexico