Selumetinib in Treating Patients With Recurrent or Persistent Endometrial Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01011933
First received: November 10, 2009
Last updated: May 9, 2014
Last verified: December 2013
  Purpose

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


Condition Intervention Phase
Endometrial Adenocarcinoma
Endometrial Adenosquamous Cell Carcinoma
Endometrial Clear Cell Carcinoma
Recurrent Endometrial Carcinoma
Drug: selumetinib
Other: diagnostic laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Evaluation of AZD6244 (NSC #748727, IND #77782) in the Treatment of Recurrent or Persistent Endometrial Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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.


  • Objective Tumor Response Rate Assessed by RECIST [ Time Frame: From study entry, assessed up to 5 years ] [ Designated as safety issue: No ]
    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.

  • Frequency and Severity of Adverse Effects as Assessed by CTCAE v3.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Duration of Progression-free Survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Duration of Overall Survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Reason Off Study Therapy [ Time Frame: from study entry until end of study treatment ] [ Designated as safety issue: No ]
  • Patient Vital Status [ Time Frame: Study entry up to 2 years ] [ Designated as safety issue: No ]
    Patients alive or dead after 24 months from time of study entry.


Enrollment: 54
Study Start Date: September 2009
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: selumetinib
Given PO
Other Names:
  • ARRY-142886
  • AZD6244
Other: diagnostic laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01011933

  Show 71 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Robert Coleman Gynecologic Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01011933     History of Changes
Other Study ID Numbers: NCI-2011-01958, NCI-2011-01958, CDR0000651456, GOG-0229H, GOG-0229H, U10CA027469
Study First Received: November 10, 2009
Results First Received: August 21, 2013
Last Updated: May 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Carcinoma, Adenosquamous
Adenocarcinoma, Clear Cell
Adenomyoepithelioma
Endometrial Neoplasms
Uterine Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Complex and Mixed
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female

ClinicalTrials.gov processed this record on September 14, 2014