FIGO Grade 1 Endometrial Endometrioid AdenocarcinomaPhase 1/2NCT05538897
Testing the Addition of the AKT Inhibitor, Ipatasertib, to Treatment With the Hormonal Agent Megestrol Acetate for Recurrent or Metastatic Endometrial Cancers
A Phase 1/2 study testing Biospecimen Collection, Computed Tomography and Ipatasertib in people with FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma and FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma, run by National Cancer Institute (NCI) at 152 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma, FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma, Metastatic Endometrial Endometrioid Adenocarcinoma
- What is being tested?
- Biospecimen Collection, Computed Tomography and Ipatasertib
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 152 sitesUnited States
- Study dates
- 31 Mar 2023to 31 Jan 2027
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
152 sites in 1 country.
152 sites in 1 country
United States152 sites
Summa Health System - Akron Campus
Akron, Ohio, 44304
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
Community Hospital of Anaconda
Anaconda, Montana, 59711
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109
Augusta University Medical Center
Augusta, Georgia, 30912
Harold Alfond Center for Cancer Care
Augusta, Maine, 04330
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045
Bronson Battle Creek
Battle Creek, Michigan, 49017
UHHS-Chagrin Highlands Medical Center
Beachwood, Ohio, 44122
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600
Billings Clinic Cancer Center
Billings, Montana, 59101
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, 83605
Cooper Hospital University Medical Center
Camden, New Jersey, 08103
IU Health North Hospital
Carmel, Indiana, 46032
Miami Valley Hospital South
Centerville, Ohio, 45459
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Geauga Hospital
Chardon, Ohio, 44024
Medical University of South Carolina
Charleston, South Carolina, 29425
Vandalia Health/CAMC Institute for Academic Medicine
Charleston, West Virginia, 25304
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
Northwestern University
Chicago, Illinois, 60611
University of Illinois
Chicago, Illinois, 60612
Good Samaritan Hospital - Cincinnati
Cincinnati, Ohio, 45220
Case Western Reserve University
Cleveland, Ohio, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814
MU Health - University Hospital/Ellis Fischel Cancer Center
Columbia, Missouri, 65212
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Riverside Methodist Hospital
Columbus, Ohio, 43214
Atrium Health Cabarrus/LCI-Concord
Concord, North Carolina, 28025
Mercy Hospital
Coon Rapids, Minnesota, 55433
Parkland Memorial Hospital
Dallas, Texas, 75235
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Carle at The Riverfront
Danville, Illinois, 61832
Miami Valley Hospital
Dayton, Ohio, 45409
Miami Valley Hospital North
Dayton, Ohio, 45415
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526
Decatur Memorial Hospital
Decatur, Illinois, 62526
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, 60115
Iowa Methodist Medical Center
Des Moines, Iowa, 50309
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309
Fairview Southdale Hospital
Edina, Minnesota, 55435
Swedish Cancer Institute-Edmonds
Edmonds, Washington, 98026
Carle Physician Group-Effingham
Effingham, Illinois, 62401
Crossroads Cancer Center
Effingham, Illinois, 62401
Highlands Oncology Group - Fayetteville
Fayetteville, Arkansas, 72703
Parkview Regional Medical Center
Fort Wayne, Indiana, 46845
UT Southwestern/Simmons Cancer Center-Fort Worth
Fort Worth, Texas, 76104
Atrium Medical Center-Middletown Regional Hospital
Franklin, Ohio, 45005-1066
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, 83619
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134
Goshen Center for Cancer Care
Goshen, Indiana, 46526
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Grand Rapids, Michigan, 49503
Trinity Health Grand Rapids Hospital
Grand Rapids, Michigan, 49503
Northwestern Medicine Grayslake Outpatient Center
Grayslake, Illinois, 60030
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405
Miami Valley Cancer Care and Infusion
Greenville, Ohio, 45331
Lyndon Baines Johnson General Hospital
Houston, Texas, 77026-1967
Memorial Hermann Texas Medical Center
Houston, Texas, 77030
UT MD Anderson Cancer Center
Houston, Texas, 77030
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
Swedish Cancer Institute-Issaquah
Issaquah, Washington, 98029
MU Health Care Goldschmidt Cancer Center
Jefferson City, Missouri, 65109
Jefferson Hospital
Jefferson Hills, Pennsylvania, 15025
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007
West Michigan Cancer Center
Kalamazoo, Michigan, 49007
Beacon Kalamazoo Cancer Center
Kalamazoo, Michigan, 49009
University of Kansas Cancer Center
Kansas City, Kansas, 66160
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois, 60045
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938
UH Seidman Cancer Center at Lake Health Mentor Campus
Mentor, Ohio, 44060
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho, 83642
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455
Community Medical Center
Missoula, Montana, 59804
Forbes Hospital
Monroeville, Pennsylvania, 15146
Trinity Health Muskegon Hospital
Muskegon, Michigan, 49444
Sarasota Memorial Hospital-Venice
N. Venice, Florida, 34275
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho, 83687
Saint Luke's Cancer Institute - Nampa
Nampa, Idaho, 83687
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Corewell Health Lakeland Hospitals - Niles Hospital
Niles, Michigan, 49120
Cancer and Hematology Centers of Western Michigan - Norton Shores
Norton Shores, Michigan, 49444
Cancer Care Center of O'Fallon
O'Fallon, Illinois, 62269
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Saint Alphonsus Cancer Care Center-Ontario
Ontario, Oregon, 97914
Northwestern Medicine Orland Park
Orland Park, Illinois, 60462
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
West Penn Hospital
Pittsburgh, Pennsylvania, 15224
Providence Portland Medical Center
Portland, Oregon, 97213
Providence Saint Vincent Medical Center
Portland, Oregon, 97225
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, 83854
Women and Infants Hospital
Providence, Rhode Island, 02905
Corewell Health Reed City Hospital
Reed City, Michigan, 49677
UT Southwestern Clinical Center at Richardson/Plano
Richardson, Texas, 75080
VCU Massey Cancer Center at Stony Point
Richmond, Virginia, 23235
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
Carilion Roanoke Memorial Hospital
Roanoke, Virginia, 24033
University of Rochester
Rochester, New York, 14642
Highlands Oncology Group - Rogers
Rogers, Arkansas, 72758
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
Saint Joseph, Michigan, 49085
Corewell Health Lakeland Hospitals - Saint Joseph Hospital
Saint Joseph, Michigan, 49085
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416
Regions Hospital
Saint Paul, Minnesota, 55101
United Hospital
Saint Paul, Minnesota, 55102
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho, 83864
Florida Cancer Specialists - Sarasota Downtown
Sarasota, Florida, 34239
FPG - Surgical Oncology Clinics Gynecologic Oncology Surgery
Sarasota, Florida, 34239
Sarasota Memorial Hospital
Sarasota, Florida, 34239
MaineHealth Maine Medical Center- Scarborough
Scarborough, Maine, 04074
Swedish Medical Center-First Hill
Seattle, Washington, 98122
Memorial Hospital of South Bend
South Bend, Indiana, 46601
Highlands Oncology Group
Springdale, Arkansas, 72762
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Springfield Clinic
Springfield, Illinois, 62702
Springfield Memorial Hospital
Springfield, Illinois, 62781
Mercy Hospital Springfield
Springfield, Missouri, 65804
Mercy Hospital South
St Louis, Missouri, 63128
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
State University of New York Upstate Medical University
Syracuse, New York, 13210
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461
Montefiore Medical Center-Weiler Hospital
The Bronx, New York, 10461
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467
Munson Medical Center
Traverse City, Michigan, 49684
Upper Valley Medical Center
Troy, Ohio, 45373
Banner University Medical Center - Tucson
Tucson, Arizona, 85719
University of Arizona Cancer Center-North Campus
Tucson, Arizona, 85719
Oklahoma Cancer Specialists and Research Institute-Tulsa
Tulsa, Oklahoma, 74146
Carle Cancer Center
Urbana, Illinois, 61801
Florida Cancer Specialists - Venice Pinebrook
Venice, Florida, 34275
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555
UH Seidman Cancer Center at Saint John Medical Center
Westlake, Ohio, 44145
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205
Wexford Health and Wellness Pavilion
Wexford, Pennsylvania, 15090
Asplundh Cancer Pavilion
Willow Grove, Pennsylvania, 19090
Minnesota Oncology Hematology PA-Woodbury
Woodbury, Minnesota, 55125
University of Michigan Health - West
Wyoming, Michigan, 49519
About this study
Official title: A Phase IB and Randomized Phase II Trial of Megestrol Acetate With or Without Ipatasertib in Recurrent or Metastatic Endometrioid Endometrial Cancer
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.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the toxicity of ipatasertib in combination with megestrol acetate in women with metastatic grade 1-2 endometrioid endometrial cancer and establish the recommended phase II dose. (Phase I) II. Compare the progression free survival of the combination of ipatasertib with megestrol acetate to megestrol acetate alone among women with metastatic grade 1-2 endometrioid adenocarcinoma of the endometrium. (Phase II) III. Compare the toxicity of the combination of ipatasertib with megestrol acetate to megestrol acetate alone. (Phase II)
SECONDARY OBJECTIVES:
- Compare objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 between the two arms.
II. Examine the pharmacokinetics of ipatasertib + megestrol acetate to assess potential drug-drug interactions.
III. Assess the association between biomarkers and response to therapy.
EXPLORATORY OBJECTIVE:
- Explore whether pS6/total S6 and pPRAS40/total PRAS40 expression is impacted by the use of ipatasertib and megestrol acetate.
OUTLINE: This is a phase Ib, dose de-escalation study of ipatasertib followed by a phase II study.
PHASE Ib: Patients receive megestrol acetate orally (PO) once daily (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 computed tomography (CT) or magnetic resonance imaging (MRI) during screening, on study, and during follow-up. Patients also undergo collection of blood samples throughout the trial.
PHASE II: Patients are randomized to 1 of 2 arms.
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.
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.
After completion of study treatment, patients are followed up at 30 days for the phase I study. Patients are followed up every 3 months for 2 years, then every 6 months for 3 years for the phase II study.
- Conditions
- FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma, FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma, Metastatic Endometrial Endometrioid Adenocarcinoma, Recurrent Endometrial Endometrioid Adenocarcinoma
- Being tested
- Biospecimen Collection, Computed Tomography, Ipatasertib, Magnetic Resonance Imaging, Megestrol Acetate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood sample collection
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT scan
IpatasertibDrug
Also called GDC 0068, GDC-0068, GDC0068, RG 7440
Given PO
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
Megestrol AcetateDrug
Also called 17-Hydroxy-6-methylpregna-4,6-diene-3,20-dione acetate, 17.alpha.-Acetoxy-6-methylpregna-4,6-diene-3,20-dione, 6-Dehydro-6-methyl-17.alpha.-acetoxyprogesterone, 6-Methyl-6-dehydro-17.alpha.-acetoxyprogesterone
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Phase Ib (megestrol acetate, ipatasertib) | Experimental | 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. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Ipatasertib; Procedure: Magnetic Resonance Imaging; Drug: Megestrol Acetate |
| Phase II (megestrol acetate) | Active comparator | 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. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Megestrol Acetate |
| Phase II (megestrol acetate, ipatasertib) | Experimental | 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. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Ipatasertib; Procedure: Magnetic Resonance Imaging; Drug: Megestrol Acetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 5 years
Secondary outcomes (3)
Pharmacokinetics of ipatasertib + megestrol acetate (Phase Ib)
Examine the pharmacokinetics of ipatasertib + megestrol acetate to assess potential drug-drug interactions. This data will be summarized descriptively.
Measured: On cycle 1, day 8
Objective response rate (Phase II)
Response is defined as complete response or partial response (CR+PR) evaluated by Response Evaluation Criteria in Solid Tumors version 1.1. A logistic model will be used to estimate the relative odds of responding (CR+PR) to megestrol acetate + ipatasertib relative to megestrol acetate alone after adjusting for prior progesterone therapy.
Measured: Up to 5 years
Biomarkers (Phase II)
The association between biomarkers and response to therapy will be assessed. Integrated biomarker endpoints include: PTEN immunohistochemistry, estrogen receptor and progesterone receptor, whole exome sequencing, ribonucleic acid sequencing. Proportional hazards models will be used to examine the prognostic association of integrated biomarkers with PFS; and interactions between markers and treatment arm will be used to examine the markers' predictive association with PFS.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2022
- Study start31 Mar 2023
- Primary completion31 Jan 2027 (estimated)
- Study completion31 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for FIGO Grade 1 Endometrial Endometrioid AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 96 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Collaborators
- NRG Oncology
- Responsible party
- Sponsor
- Investigators
- Michaela O Grinsfelder, Principal investigator, NRG Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05538897
- Sponsor's protocol ID
- NCI-2022-07505
- Other IDs
- NCI-2022-07505, NRG-GY028, NRG-GY028, U10CA180868
- Status last verified
- Jun 2026
- First submitted
- 13 Sep 2022
- Last updated
- 1 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.