Testing the Addition of the AKT Inhibitor, Ipatasertib, to Treatment With the Hormonal Agent Megestrol Acetate for Recurrent or Metastatic Endometrial Cancers
A Phase IB and Randomized Phase II Trial of Megestrol Acetate With or Without Ipatasertib in Recurrent or Metastatic Endometrioid Endometrial Cancer
3 other identifiers
interventional
96
1 country
152
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2023
Longer than P75 for phase_1
152 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 13, 2022
CompletedFirst Posted
Study publicly available on registry
September 14, 2022
CompletedStudy Start
First participant enrolled
March 31, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 31, 2027
April 13, 2026
December 1, 2025
3.8 years
September 13, 2022
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (4)
Incidence of adverse events (AEs) (Phase Ib)
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.
Up to 5 years
Maximum tolerated dose for phase II (Phase Ib)
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.
Up to 5 years
Progression free survival (PFS) (Phase II)
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.
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
Incidence of AEs (Phase II)
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.
Up to 5 years
Secondary Outcomes (3)
Pharmacokinetics of ipatasertib + megestrol acetate (Phase Ib)
On cycle 1, day 8
Objective response rate (Phase II)
Up to 5 years
Biomarkers (Phase II)
Up to 5 years
Other Outcomes (1)
pS6/total S6 and pPRAS40/total PRAS40 expression (Phase II)
Up to 5 years
Study Arms (3)
Phase Ib (megestrol acetate, ipatasertib)
EXPERIMENTALPatients 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.
Phase II (megestrol acetate)
ACTIVE COMPARATORArm 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.
Phase II (megestrol acetate, ipatasertib)
EXPERIMENTALArm 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.
Interventions
Undergo blood sample collection
Undergo CT scan
Given PO
Given PO
Undergo MRI
Eligibility Criteria
You may qualify if:
- 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
- +8 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- National Cancer Institute (NCI)lead
- NRG Oncologycollaborator
Study Sites (152)
Banner University Medical Center - Tucson
Tucson, Arizona, 85719, United States
University of Arizona Cancer Center-North Campus
Tucson, Arizona, 85719, United States
Highlands Oncology Group - Fayetteville
Fayetteville, Arkansas, 72703, United States
Highlands Oncology Group - Rogers
Rogers, Arkansas, 72758, United States
Highlands Oncology Group
Springdale, Arkansas, 72762, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610, United States
Sarasota Memorial Hospital-Venice
N. Venice, Florida, 34275, United States
Florida Cancer Specialists - Sarasota Downtown
Sarasota, Florida, 34236, United States
First Physicians Group-Sarasota
Sarasota, Florida, 34239, United States
Sarasota Memorial Hospital
Sarasota, Florida, 34239, United States
Florida Cancer Specialists - Venice Pinebrook
Venice, Florida, 34275, United States
Augusta University Medical Center
Augusta, Georgia, 30912, United States
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712, United States
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, 83605, United States
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814, United States
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, 83619, United States
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho, 83642, United States
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho, 83687, United States
Saint Luke's Cancer Institute - Nampa
Nampa, Idaho, 83687, United States
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, 83854, United States
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho, 83864, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Illinois
Chicago, Illinois, 60612, United States
Carle at The Riverfront
Danville, Illinois, 61832, United States
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526, United States
Decatur Memorial Hospital
Decatur, Illinois, 62526, United States
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, 60115, United States
Carle Physician Group-Effingham
Effingham, Illinois, 62401, United States
Crossroads Cancer Center
Effingham, Illinois, 62401, United States
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134, United States
Northwestern Medicine Grayslake Outpatient Center
Grayslake, Illinois, 60030, United States
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois, 60045, United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938, United States
Cancer Care Center of O'Fallon
O'Fallon, Illinois, 62269, United States
Northwestern Medicine Orland Park
Orland Park, Illinois, 60462, United States
Southern Illinois University School of Medicine
Springfield, Illinois, 62702, United States
Springfield Clinic
Springfield, Illinois, 62702, United States
Springfield Memorial Hospital
Springfield, Illinois, 62781, United States
Carle Cancer Center
Urbana, Illinois, 61801, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555, United States
IU Health North Hospital
Carmel, Indiana, 46032, United States
Parkview Regional Medical Center
Fort Wayne, Indiana, 46845, United States
Goshen Center for Cancer Care
Goshen, Indiana, 46526, United States
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202, United States
Memorial Hospital of South Bend
South Bend, Indiana, 46601, United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023, United States
Iowa Methodist Medical Center
Des Moines, Iowa, 50309, United States
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
Harold Alfond Center for Cancer Care
Augusta, Maine, 04330, United States
MaineHealth Maine Medical Center- Scarborough
Scarborough, Maine, 04074, United States
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600, United States
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109, United States
Bronson Battle Creek
Battle Creek, Michigan, 49017, United States
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Grand Rapids, Michigan, 49503, United States
Trinity Health Grand Rapids Hospital
Grand Rapids, Michigan, 49503, United States
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007, United States
West Michigan Cancer Center
Kalamazoo, Michigan, 49007, United States
Beacon Kalamazoo Cancer Center
Kalamazoo, Michigan, 49009, United States
Trinity Health Muskegon Hospital
Muskegon, Michigan, 49444, United States
Corewell Health Lakeland Hospitals - Niles Hospital
Niles, Michigan, 49120, United States
Cancer and Hematology Centers of Western Michigan - Norton Shores
Norton Shores, Michigan, 49444, United States
Corewell Health Reed City Hospital
Reed City, Michigan, 49677, United States
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
Saint Joseph, Michigan, 49085, United States
Corewell Health Lakeland Hospitals - Saint Joseph Hospital
Saint Joseph, Michigan, 49085, United States
Munson Medical Center
Traverse City, Michigan, 49684, United States
University of Michigan Health - West
Wyoming, Michigan, 49519, United States
Mercy Hospital
Coon Rapids, Minnesota, 55433, United States
Fairview Southdale Hospital
Edina, Minnesota, 55435, United States
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416, United States
Regions Hospital
Saint Paul, Minnesota, 55101, United States
United Hospital
Saint Paul, Minnesota, 55102, United States
Minnesota Oncology Hematology PA-Woodbury
Woodbury, Minnesota, 55125, United States
MU Health - University Hospital/Ellis Fischel Cancer Center
Columbia, Missouri, 65212, United States
MU Health Care Goldschmidt Cancer Center
Jefferson City, Missouri, 65109, United States
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154, United States
Mercy Hospital Springfield
Springfield, Missouri, 65804, United States
Mercy Hospital South
St Louis, Missouri, 63128, United States
Mercy Hospital Saint Louis
St Louis, Missouri, 63141, United States
Community Hospital of Anaconda
Anaconda, Montana, 59711, United States
Billings Clinic Cancer Center
Billings, Montana, 59101, United States
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715, United States
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405, United States
Community Medical Center
Missoula, Montana, 59804, United States
Cooper Hospital University Medical Center
Camden, New Jersey, 08103, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106, United States
University of Rochester
Rochester, New York, 14642, United States
State University of New York Upstate Medical University
Syracuse, New York, 13210, United States
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461, United States
Montefiore Medical Center-Weiler Hospital
The Bronx, New York, 10461, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203, United States
Atrium Health Cabarrus/LCI-Concord
Concord, North Carolina, 28025, United States
Summa Health System - Akron Campus
Akron, Ohio, 44304, United States
UHHS-Chagrin Highlands Medical Center
Beachwood, Ohio, 44122, United States
Miami Valley Hospital South
Centerville, Ohio, 45459, United States
Geauga Hospital
Chardon, Ohio, 44024, United States
Good Samaritan Hospital - Cincinnati
Cincinnati, Ohio, 45220, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Riverside Methodist Hospital
Columbus, Ohio, 43214, United States
Miami Valley Hospital
Dayton, Ohio, 45409, United States
Miami Valley Hospital North
Dayton, Ohio, 45415, United States
Atrium Medical Center-Middletown Regional Hospital
Franklin, Ohio, 45005-1066, United States
Miami Valley Cancer Care and Infusion
Greenville, Ohio, 45331, United States
UH Seidman Cancer Center at Lake Health Mentor Campus
Mentor, Ohio, 44060, United States
Upper Valley Medical Center
Troy, Ohio, 45373, United States
UH Seidman Cancer Center at Saint John Medical Center
Westlake, Ohio, 44145, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Oklahoma Cancer Specialists and Research Institute-Tulsa
Tulsa, Oklahoma, 74146, United States
Saint Alphonsus Cancer Care Center-Ontario
Ontario, Oregon, 97914, United States
Providence Portland Medical Center
Portland, Oregon, 97213, United States
Providence Saint Vincent Medical Center
Portland, Oregon, 97225, United States
Jefferson Hospital
Jefferson Hills, Pennsylvania, 15025, United States
Forbes Hospital
Monroeville, Pennsylvania, 15146, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212, United States
West Penn Hospital
Pittsburgh, Pennsylvania, 15224, United States
Wexford Health and Wellness Pavilion
Wexford, Pennsylvania, 15090, United States
Asplundh Cancer Pavilion
Willow Grove, Pennsylvania, 19090, United States
Women and Infants Hospital
Providence, Rhode Island, 02905, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Parkland Memorial Hospital
Dallas, Texas, 75235, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
UT Southwestern/Simmons Cancer Center-Fort Worth
Fort Worth, Texas, 76104, United States
Lyndon Baines Johnson General Hospital
Houston, Texas, 77026-1967, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Memorial Hermann Texas Medical Center
Houston, Texas, 77030, United States
UT Southwestern Clinical Center at Richardson/Plano
Richardson, Texas, 75080, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
VCU Massey Cancer Center at Stony Point
Richmond, Virginia, 23235, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
Carilion Roanoke Memorial Hospital
Roanoke, Virginia, 24033, United States
Swedish Cancer Institute-Edmonds
Edmonds, Washington, 98026, United States
Swedish Cancer Institute-Issaquah
Issaquah, Washington, 98029, United States
Swedish Medical Center-First Hill
Seattle, Washington, 98122, United States
West Virginia University Charleston Division
Charleston, West Virginia, 25304, United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Michaela O Grinsfelder
NRG Oncology
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 13, 2022
First Posted
September 14, 2022
Study Start
March 31, 2023
Primary Completion (Estimated)
January 31, 2027
Study Completion (Estimated)
January 31, 2027
Last Updated
April 13, 2026
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.