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Endometrial AdenocarcinomaPhase 2NCT01011933

Selumetinib in Treating Patients With Recurrent or Persistent Endometrial Cancer

A Phase 2 study testing Diagnostic Laboratory Biomarker Analysis and Selumetinib in people with Endometrial Adenocarcinoma and Endometrial Adenosquamous Carcinoma, run by National Cancer Institute (NCI) at 72 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Diagnostic Laboratory Biomarker Analysis and Selumetinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
72 sitesUnited States
Study dates
Sep 2009to Jan 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Histologically confirmed* endometrial epithelial carcinoma, including any of the following cell types:
  • Endometrioid adenocarcinoma
  • Serous adenocarcinoma
  • Undifferentiated carcinoma
  • Clear cell adenocarcinoma
  • Mixed epithelial carcinoma
Show all 69Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

72 sites in 1 country.

72 sites in 1 country

United States72 sites

  • Abington Memorial Hospital

    Abington, Pennsylvania, 19001

  • Saint Joseph Mercy Hospital

    Ann Arbor, Michigan, 48106-0995

  • Michigan Cancer Research Consortium CCOP

    Ann Arbor, Michigan, 48106

  • University of Colorado Cancer Center - Anschutz Cancer Pavilion

    Aurora, Colorado, 80045

  • MedStar Franklin Square Medical Center/Weinberg Cancer Institute

    Baltimore, Maryland, 21237

  • State University of New York Downstate Medical Center

    Brooklyn, New York, 11203

  • Bryn Mawr Hospital

    Bryn Mawr, Pennsylvania, 19010

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • University of Cincinnati

    Cincinnati, Ohio, 45267

  • Medical Oncology and Hematology Associates-West Des Moines

    Clive, Iowa, 50325

  • Mercy Cancer Center-West Lakes

    Clive, Iowa, 50325

  • Riverside Methodist Hospital

    Columbus, Ohio, 43214

  • Oakwood Hospital and Medical Center

    Dearborn, Michigan, 48124

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • Iowa-Wide Oncology Research Coalition NCORP

    Des Moines, Iowa, 50309

  • Medical Oncology and Hematology Associates-Des Moines

    Des Moines, Iowa, 50309

  • Medical Oncology and Hematology Associates-Laurel

    Des Moines, Iowa, 50314

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • Iowa Lutheran Hospital

    Des Moines, Iowa, 50316

  • Saint John Hospital and Medical Center

    Detroit, Michigan, 48236

  • Hurley Medical Center

    Flint, Michigan, 48502

  • Genesys Regional Medical Center-West Flint Campus

    Flint, Michigan, 48532

  • Hartford Hospital

    Hartford, Connecticut, 06102

  • Smilow Cancer Hospital Care Center at Saint Francis

    Hartford, Connecticut, 06105

  • Sudarshan K Sharma MD Limted-Gynecologic Oncology

    Hinsdale, Illinois, 60521

  • Lyndon Baines Johnson General Hospital

    Houston, Texas, 77026-1967

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Indiana University/Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Saint Vincent Oncology Center

    Indianapolis, Indiana, 46260

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Allegiance Health

    Jackson, Michigan, 49201

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Borgess Medical Center

    Kalamazoo, Michigan, 49001

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

  • Truman Medical Center

    Kansas City, Missouri, 64108

  • Saint Luke's Hospital of Kansas City

    Kansas City, Missouri, 64111

  • Saint Joseph Health Center

    Kansas City, Missouri, 64114

  • North Kansas City Hospital

    Kansas City, Missouri, 64116

  • Heartland Hematology and Oncology Associates Incorporated

    Kansas City, Missouri, 64118

  • Research Medical Center

    Kansas City, Missouri, 64132

  • Sparrow Hospital

    Lansing, Michigan, 48912

  • Women's Cancer Center of Nevada

    Las Vegas, Nevada, 89169

  • Saint Luke's East - Lee's Summit

    Lee's Summit, Missouri, 64086

  • Liberty Hospital

    Liberty, Missouri, 64068

  • Saint Mary Mercy Hospital

    Livonia, Michigan, 48154

  • Los Angeles County-USC Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • The Hospital of Central Connecticut

    New Britain, Connecticut, 06050

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Menorah Medical Center

    Overland Park, Kansas, 66209

  • Saint Luke's South Hospital

    Overland Park, Kansas, 66213

  • Paoli Memorial Hospital

    Paoli, Pennsylvania, 19301

  • Saint Joseph Mercy Oakland

    Pontiac, Michigan, 48341

  • Saint Joseph Mercy Port Huron

    Port Huron, Michigan, 48060

  • Kansas City NCI Community Oncology Research Program

    Prairie Village, Kansas, 66208

  • Women and Infants Hospital

    Providence, Rhode Island, 02905

  • Saint Mary's of Michigan

    Saginaw, Michigan, 48601

  • Heartland Regional Medical Center

    Saint Joseph, Missouri, 64506

  • Saint Joseph Oncology Inc

    Saint Joseph, Missouri, 64507

  • Memorial Medical Center

    Springfield, Illinois, 62781

  • Cancer Research for the Ozarks NCORP

    Springfield, Missouri, 65804

  • CoxHealth South Hospital

    Springfield, Missouri, 65807

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Oklahoma Cancer Specialists and Research Institute-Tulsa

    Tulsa, Oklahoma, 74146

  • Saint John Macomb-Oakland Hospital

    Warren, Michigan, 48093

  • MedStar Washington Hospital Center

    Washington D.C., District of Columbia, 20010

  • Methodist West Hospital

    West Des Moines, Iowa, 50266-7700

  • Mercy Medical Center-West Lakes

    West Des Moines, Iowa, 50266

  • Lankenau Medical Center

    Wynnewood, Pennsylvania, 19096

  • Main Line Health NCORP

    Wynnewood, Pennsylvania, 19096

Other trials in United States

About this study

Official title: A Phase II Evaluation of AZD6244 (NSC #748727) in the Treatment of Recurrent or Persistent Endometrial Carcinoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

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

EXPLORATORY OBJECTIVES:

  1. 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.

Being tested
Diagnostic Laboratory Biomarker Analysis, Selumetinib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Diagnostic Laboratory Biomarker AnalysisOther

    Correlative studies

  • SelumetinibDrug

    Also called ARRY-142886, AZD6244, MEK Inhibitor AZD6244

    Given PO

Study groups in NCT01011933
Study groupRoleWhat they receive
Treatment (selumetinib)ExperimentalPatients 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.
Receives: Other: Diagnostic Laboratory Biomarker Analysis; Drug: Selumetinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With or Without Progression-free Survival for > 6 Months by Response Evaluation Criteria for Solid Tumors (RECIST)

    Number of participants who survived progression-free for more than 6 months.

    Progression is defined using Response Evaluation Criteria for Solid Tumors (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions in the opinion of the treating physician, or global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression.

    Measured: > 6 months from study entry

  2. Objective Tumor Response Rate Assessed by RECIST

    Per Response Evaluation Criteria In Solid Tumors (RECIST) Criteria: Complete Response (CR) is disappearance of all target and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Normalization of CA125, if elevated at study entry, is required; Partial Response (PR) is at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD; Increasing Disease is at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD or the appearance of new lesions within 8 weeks of study entry; Stable Disease is any condition not meeting the above criteria.

    Measured: From study entry, assessed up to 5 years

  3. Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0

    Measured: Each cycle during treatment and 30 days after the last treatment.

Secondary outcomes (2)

  1. Duration of Progression-free Survival

    Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions.

    Measured: Every other cycle for the first 6 months; then every 3 months thereafter for up to 5 years

  2. Duration of Overall Survival

    Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.

    Measured: Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Nov 2009 (estimated)
  2. Study startSep 2009
  3. Primary completionJan 2016
  4. Study completionJan 2016

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01011933
Sponsor's protocol ID
NCI-2011-01958
Other IDs
NCI-2011-01958, GOG-0229H, CDR0000651456, GOG-0229H, GOG-0229H, U10CA180868, U10CA027469
Status last verified
Jul 2019
First submitted
10 Nov 2009
Last updated
23 Jul 2019
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 25887099

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Diagnostic Laboratory Biomarker Analysis and Selumetinib in people with Endometrial Adenocarcinoma and Endometrial Adenosquamous Carcinoma, run by National Cancer Institute (NCI) at 72 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 69 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 72 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With or Without Progression-free Survival for > 6 Months by Response Evaluation Criteria for Solid Tumors (RECIST) (time frame: > 6 months from study entry). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01011933, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2019.

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