Selumetinib in Treating Patients With Recurrent or Persistent Endometrial Cancer

NCT ID: NCT01011933

Last Updated: 2019-07-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2016-01-31

Brief Summary

This phase II trial is studying how well selumetinib works in treating patients with recurrent or persistent endometrial cancer that has come back or is persistent. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the activity of AZD6244 (selumetinib) for patients with recurrent or persistent endometrial cancer with the frequency of patients who survive progression-free for at least 6 months after initiating therapy or have objective tumor response.

II. To determine the nature and degree of toxicity of AZD6244 as assessed by CTCAE v3.0 in this cohort of patients.

SECONDARY OBJECTIVE:

I. To determine the duration of progression-free survival and overall survival.

EXPLORATORY OBJECTIVES:

I. To explore the associations between select biomarkers and response to AZD6244 (progression-free survival status >6 months and objective tumor response), measures of clinical outcome (progression-free survival and overall survival) or disease status including histologic cell type.

II. Mutations and single nucleotide polymorphisms in BRAF, KRAS2, FGFR2, PI3KCA, AKT1, AKT2, AKT3 and PTEN in DNA from formalin-fixed and paraffin-embedded (FFPE) tumor and/or normal blood cells.

III. Immunohistochemical expression of ERK, pERK, GSK3betta, pGSK3betta, PR-A, PR-B, pPR, ER-alpha, ER-beta, BRAF, KRAS, PTEN, EGFR, pEGFR, EGF, PELP1 and MTA1s in FFPE tumor.

IV. To explore the relationship among the panel of biomarkers evaluated in this cohort including mutations and single nucleotide polymorphisms in BRAF, KRAS2, FGFR2, PI3KCA, AKT1, AKT2, AKT3 and PTEN as well as immunohistochemical expression of ERK, pERK, GSK3betta, pGSK3betta, PR-A, PR-B, pPR, ER-alpha, ER-beta, BRAF, KRAS, PTEN, EGFR, pEGFR, EGF, PELP1 and MTA1s.

OUTLINE: This is a multicenter study.

Patients receive selumetinib orally (PO) twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Blood and archived tumor tissue samples are collected for biomarker studies.

After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Conditions

Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Recurrent Uterine Corpus Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (selumetinib)

Patients receive selumetinib PO twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Blood and archived tumor tissue samples are collected for biomarker studies.

Group Type: EXPERIMENTAL

Diagnostic Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Selumetinib

Intervention Type: DRUG

Given PO

Interventions

Diagnostic Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Selumetinib

Given PO

Intervention Type: DRUG

Other Intervention Names

ARRY-142886; AZD6244; MEK Inhibitor AZD6244

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed* endometrial epithelial carcinoma, including any of the following cell types:

• Endometrioid adenocarcinoma
• Serous adenocarcinoma
• Undifferentiated carcinoma
• Clear cell adenocarcinoma
• Mixed epithelial carcinoma
• Adenocarcinoma not otherwise specified
• Mucinous adenocarcinoma
• Squamous cell carcinoma
• Transitional cell carcinoma
• Mesonephric carcinoma
• Recurrent or persistent disease that is refractory to curative therapy or established treatments
• Measurable disease, defined as ≥ 1 lesion that can be measured in ≥ 1 dimension (longest dimension to be recorded)

• Each lesion must be ≥ 20 mm when measured by conventional techniques (palpation, plain x-ray, CT scan, or MRI) OR ≥ 10 mm when measured by spiral CT scan
• Must have ≥ 1 target lesion to be used to assess response, as defined by RECIST criteria

• Tumors within a previously irradiated field are designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence ≥ 90 days following completion of radiotherapy
• Must have received 1 prior chemotherapeutic regimen for the management of endometrial carcinoma

• Chemotherapy administered as a radiosensitizer in conjunction with primary radiotherapy is considered a systemic chemotherapy regimen
• Not eligible for a higher priority GOG protocol, if one exists (e.g., any active phase III GOG protocol for the same patient population)
• No prior or concurrent CNS disease (treated or untreated) by physical examination, including primary brain tumor or brain metastases
• GOG performance status (PS) 0-2 (for patients who received 1 prior treatment regimen)
• GOG PS 0-1 (for patients who received 2 prior treatment regimens)
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• SGOT ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• PT/INR ≤ 1.5 OR in-range INR (between 2 and 3) if patient is on a stable dose of therapeutic warfarin
• PTT ≤ 1.5 times ULN
• Oxygen saturation ≥ 88% on room air
• QTc < 450 msec by EKG
• LVEF normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy
• No neuropathy (sensory or motor) > grade 1
• No active infection requiring antibiotics

• Uncomplicated urinary tract infection allowed
• No other invasive malignancy within the past 5 years except for nonmelanoma skin cancer
• No serious, non-healing wound, ulcer, or bone fracture
• No history of abdominal fistula or gastrointestinal perforation
• No intra-abdominal abscess within the past 28 days
• No active bleeding or pathological condition that would carry a high risk of bleeding (e.g., bleeding disorder, coagulopathy, or tumor involving major vessels)
• No seizures not controlled with standard medical therapy
• No clinically significant cardiovascular disease including, but not limited to, any of the following:

• Uncontrolled hypertension, defined as systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg
• Myocardial infarction or unstable angina within the past 6 months
• NYHA class II-IV congestive heart failure
• Serious cardiac arrhythmia requiring medication, including atrial fibrillation requiring rate-controlling medication
• Peripheral vascular disease ≥ grade 2
• Cerebrovascular accident (i.e., CVA, stroke), transient ischemic attack, or subarachnoidal hemorrhage within the past 6 months
• No evidence of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row) by EKG
• Concurrent low molecular weight heparin for treatment of venous thromboembolic disease allowed provided patient is considered clinically stable on this regimen
• Recovered from prior surgery, radiotherapy, or chemotherapy
• At least 1 week since prior hormonal therapy directed at the malignant tumor
• At least 3 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C)
• At least 3 weeks since other prior therapy directed at the malignant tumor, including immunologic agents
• One prior cytotoxic regimen for the management of recurrent or persistent endometrial disease allowed
• No prior non-cytotoxic chemotherapy for the management of endometrial cancer, except hormonal therapy
• No prior anticancer therapy that contraindicates study therapy
• No prior MEK inhibitor AZD6244 or other specific MEK/ERK/MAPK pathway targeted therapy
• No prior chemotherapy for any abdominal or pelvic tumor other than for the treatment for endometrial cancer within the past 5 years

• Prior adjuvant chemotherapy for localized breast cancer allowed provided it was completed > 3 years ago AND the patient remains free of recurrent or metastatic disease
• No prior radiotherapy to any portion of the abdominal cavity or pelvis other than for the treatment of endometrial cancer within the past 5 years

• Prior radiotherapy for localized cancer of the breast, head and neck, or skin is allowed provided it was completed > 3 years ago AND the patient remains free of recurrent or metastatic disease
• No concurrent medication that may prolong the QTc interval
• No other concurrent investigational therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

NRG Oncology

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Coleman

Role: PRINCIPAL_INVESTIGATOR

NRG Oncology

Locations

Los Angeles County-USC Medical Center

Los Angeles, California, United States

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

University of Colorado Cancer Center - Anschutz Cancer Pavilion

Aurora, Colorado, United States

Hartford Hospital

Hartford, Connecticut, United States

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, United States

The Hospital of Central Connecticut

New Britain, Connecticut, United States

MedStar Washington Hospital Center

Washington D.C., District of Columbia, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Sudarshan K Sharma MD Limted-Gynecologic Oncology

Hinsdale, Illinois, United States

Memorial Medical Center

Springfield, Illinois, United States

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Saint Vincent Oncology Center

Indianapolis, Indiana, United States

Medical Oncology and Hematology Associates-West Des Moines

Clive, Iowa, United States

Mercy Cancer Center-West Lakes

Clive, Iowa, United States

Iowa Methodist Medical Center

Des Moines, Iowa, United States

Iowa-Wide Oncology Research Coalition NCORP

Des Moines, Iowa, United States

Medical Oncology and Hematology Associates-Des Moines

Des Moines, Iowa, United States

Medical Oncology and Hematology Associates-Laurel

Des Moines, Iowa, United States

Mercy Medical Center - Des Moines

Des Moines, Iowa, United States

Iowa Lutheran Hospital

Des Moines, Iowa, United States

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Methodist West Hospital

West Des Moines, Iowa, United States

Mercy Medical Center-West Lakes

West Des Moines, Iowa, United States

Menorah Medical Center

Overland Park, Kansas, United States

Saint Luke's South Hospital

Overland Park, Kansas, United States

Kansas City NCI Community Oncology Research Program

Prairie Village, Kansas, United States

MedStar Franklin Square Medical Center/Weinberg Cancer Institute

Baltimore, Maryland, United States

Saint Joseph Mercy Hospital

Ann Arbor, Michigan, United States

Michigan Cancer Research Consortium CCOP

Ann Arbor, Michigan, United States

Oakwood Hospital and Medical Center

Dearborn, Michigan, United States

Saint John Hospital and Medical Center

Detroit, Michigan, United States

Hurley Medical Center

Flint, Michigan, United States

Genesys Regional Medical Center-West Flint Campus

Flint, Michigan, United States

Allegiance Health

Jackson, Michigan, United States

Borgess Medical Center

Kalamazoo, Michigan, United States

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Sparrow Hospital

Lansing, Michigan, United States

Saint Mary Mercy Hospital

Livonia, Michigan, United States

Saint Joseph Mercy Oakland

Pontiac, Michigan, United States

Saint Joseph Mercy Port Huron

Port Huron, Michigan, United States

Saint Mary's of Michigan

Saginaw, Michigan, United States

Saint John Macomb-Oakland Hospital

Warren, Michigan, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Truman Medical Center

Kansas City, Missouri, United States

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, United States

Saint Joseph Health Center

Kansas City, Missouri, United States

North Kansas City Hospital

Kansas City, Missouri, United States

Heartland Hematology and Oncology Associates Incorporated

Kansas City, Missouri, United States

Research Medical Center

Kansas City, Missouri, United States

Saint Luke's East - Lee's Summit

Lee's Summit, Missouri, United States

Liberty Hospital

Liberty, Missouri, United States

Heartland Regional Medical Center

Saint Joseph, Missouri, United States

Saint Joseph Oncology Inc

Saint Joseph, Missouri, United States

Cancer Research for the Ozarks NCORP

Springfield, Missouri, United States

CoxHealth South Hospital

Springfield, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Women's Cancer Center of Nevada

Las Vegas, Nevada, United States

State University of New York Downstate Medical Center

Brooklyn, New York, United States

University of Cincinnati

Cincinnati, Ohio, United States

Riverside Methodist Hospital

Columbus, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Oklahoma Cancer Specialists and Research Institute-Tulsa

Tulsa, Oklahoma, United States

Abington Memorial Hospital

Abington, Pennsylvania, United States

Bryn Mawr Hospital

Bryn Mawr, Pennsylvania, United States

Paoli Memorial Hospital

Paoli, Pennsylvania, United States

Lankenau Medical Center

Wynnewood, Pennsylvania, United States

Main Line Health NCORP

Wynnewood, Pennsylvania, United States

Women and Infants Hospital

Providence, Rhode Island, United States

Lyndon Baines Johnson General Hospital

Houston, Texas, United States

M D Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

Coleman RL, Sill MW, Thaker PH, Bender DP, Street D, McGuire WP, Johnston CM, Rotmensch J. A phase II evaluation of selumetinib (AZD6244, ARRY-142886), a selective MEK-1/2 inhibitor in the treatment of recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol. 2015 Jul;138(1):30-5. doi: 10.1016/j.ygyno.2015.04.005. Epub 2015 Apr 14.

Reference Type: DERIVED

PMID: 25887099 (View on PubMed)

Other Identifiers

NCI-2011-01958

Identifier Type: REGISTRY

Identifier Source: secondary_id

GOG-0229H

Identifier Type: -

Identifier Source: secondary_id

CDR0000651456

Identifier Type: -

Identifier Source: secondary_id

GOG-0229H

Identifier Type: OTHER

Identifier Source: secondary_id

GOG-0229H

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180868

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA027469

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-01958

Identifier Type: -

Identifier Source: org_study_id