Endometrial Adenocarcinoma, Endometrial Adenosquamous Carcinoma, Endometrial Clear Cell Adenocarcinoma, Recurrent Uterine Corpus Carcinoma
Conditions
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.
Interventions
OTHERDiagnostic Laboratory Biomarker Analysis
Correlative studies
DRUGSelumetinib
Given PO
Sponsors
NRG Oncology
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Tumor Response Rate Assessed by RECIST | From study entry, assessed up to 5 years | 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. |
| Number of Participants With or Without Progression-free Survival for > 6 Months by Response Evaluation Criteria for Solid Tumors (RECIST) | > 6 months from study entry | 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. |
| Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Each cycle during treatment and 30 days after the last treatment. | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Overall Survival | 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. | Overall survival is defined as the duration of time from study entry to time of death or the date of last contact. |
| Duration of Progression-free Survival | Every other cycle for the first 6 months; then every 3 months thereafter for up to 5 years | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Off Study Therapy for Each Reason Specified. | from study entry until end of study treatment, up to 5 years. | — |
| Patient Vital Status | Study entry up to 2 years | Patients alive or dead after 24 months from time of study entry. |
Countries
United States
Participant flow
Recruitment details
The study initially opened 9/8/2009 and enrolled 28 participants. It was suspended on 5/17/2010 and re-opened 5/2/2011, enrolling an additional 26 participants until it was closed on 10/24/2011.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 50 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Improper pre-protocol Rx | 1 |
| Overall Study | Inadequate pathology | 1 |
| Overall Study | Never treated | 1 |
| Overall Study | Wrong cell type | 1 |
Baseline characteristics
| Characteristic | Treatment (Selumetinib) |
|---|---|
| Age, Continuous | 62.8 years STANDARD_DEVIATION 9.7 |
| Age, Customized 40-49 years | 4 participants |
| Age, Customized 50-59 years | 15 participants |
| Age, Customized 60-69 years | 18 participants |
| Age, Customized 70-79 years | 11 participants |
| Age, Customized 80-89 years | 2 participants |
| Cell Type Clear cell carcinoma | 1 participants |
| Cell Type Endometrioid adenocarcinoma | 31 participants |
| Cell Type Mixed epithelial carcinoma | 10 participants |
| Cell Type Serous adenocarcinoma | 8 participants |
| Region of Enrollment United States | 50 participants |
| Sex: Female, Male Female | 50 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 38 / 50 |
| serious Total, serious adverse events | 32 / 50 |
Outcome results
Primary
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.
Time frame: > 6 months from study entry
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Selumetinib) | Number of Participants With or Without Progression-free Survival for > 6 Months by Response Evaluation Criteria for Solid Tumors (RECIST) | without progression-free survival | 39 participants |
| Treatment (Selumetinib) | Number of Participants With or Without Progression-free Survival for > 6 Months by Response Evaluation Criteria for Solid Tumors (RECIST) | with progression-free survival | 11 participants |
Primary
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.
Time frame: From study entry, assessed up to 5 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Selumetinib) | Objective Tumor Response Rate Assessed by RECIST | Partial Response | 2 participants |
| Treatment (Selumetinib) | Objective Tumor Response Rate Assessed by RECIST | Stable Disease | 13 participants |
| Treatment (Selumetinib) | Objective Tumor Response Rate Assessed by RECIST | Complete Response | 1 participants |
| Treatment (Selumetinib) | Objective Tumor Response Rate Assessed by RECIST | Increase Disease | 23 participants |
| Treatment (Selumetinib) | Objective Tumor Response Rate Assessed by RECIST | Indeterminate | 11 participants |
Primary
Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0
Time frame: Each cycle during treatment and 30 days after the last treatment.
Population: Eligible and evaluable patients
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Selumetinib) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Infection | 51 Participants |
| Treatment (Selumetinib) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Auditory/Ear | 51 Participants |
| Treatment (Selumetinib) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Metabolic | 34 Participants |
| Treatment (Selumetinib) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Dermatologic | 16 Participants |
| Treatment (Selumetinib) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Genitourinary/Renal | 50 Participants |
| Treatment (Selumetinib) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Pulmonary | 40 Participants |
| Treatment (Selumetinib) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Ocular/Visual | 48 Participants |
| Treatment (Selumetinib) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Cardiac | 45 Participants |
| Treatment (Selumetinib) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Hemorrhage | 47 Participants |
| Treatment (Selumetinib) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Constitutional | 16 Participants |
| Treatment (Selumetinib) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Thrombocytopenia | 48 Participants |
| Treatment (Selumetinib) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Lymphatics | 31 Participants |
| Treatment (Selumetinib) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Pain | 33 Participants |
| Treatment (Selumetinib) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Coagulation | 51 Participants |
| Treatment (Selumetinib) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Vascular | 51 Participants |
| Treatment (Selumetinib) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Neutropenia | 45 Participants |
| Treatment (Selumetinib) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Neuropathy | 49 Participants |
| Treatment (Selumetinib) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Sexual/Reproductive | 51 Participants |
| Treatment (Selumetinib) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Anemia | 21 Participants |
| Treatment (Selumetinib) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Hepatobiliary | 51 Participants |
| Treatment (Selumetinib) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Gastrointestinal | 9 Participants |
| Treatment (Selumetinib) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Other Neurological | 44 Participants |
| Treatment (Selumetinib) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Leukopenia | 39 Participants |
| Grade 1 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Other Neurological | 5 Participants |
| Grade 1 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Metabolic | 9 Participants |
| Grade 1 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Hepatobiliary | 0 Participants |
| Grade 1 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Lymphatics | 10 Participants |
| Grade 1 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Infection | 0 Participants |
| Grade 1 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Neutropenia | 3 Participants |
| Grade 1 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Leukopenia | 11 Participants |
| Grade 1 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Sexual/Reproductive | 0 Participants |
| Grade 1 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Anemia | 10 Participants |
| Grade 1 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Pulmonary | 6 Participants |
| Grade 1 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Auditory/Ear | 0 Participants |
| Grade 1 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Vascular | 0 Participants |
| Grade 1 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Cardiac | 2 Participants |
| Grade 1 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Pain | 8 Participants |
| Grade 1 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Coagulation | 0 Participants |
| Grade 1 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Thrombocytopenia | 4 Participants |
| Grade 1 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Ocular/Visual | 1 Participants |
| Grade 1 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Constitutional | 18 Participants |
| Grade 1 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Dermatologic | 13 Participants |
| Grade 1 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Gastrointestinal | 18 Participants |
| Grade 1 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Neuropathy | 2 Participants |
| Grade 1 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Genitourinary/Renal | 0 Participants |
| Grade 1 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Hemorrhage | 4 Participants |
| Grade 2 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Pain | 6 Participants |
| Grade 2 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Other Neurological | 0 Participants |
| Grade 2 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Auditory/Ear | 1 Participants |
| Grade 2 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Lymphatics | 7 Participants |
| Grade 2 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Dermatologic | 18 Participants |
| Grade 2 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Leukopenia | 2 Participants |
| Grade 2 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Pulmonary | 3 Participants |
| Grade 2 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Vascular | 1 Participants |
| Grade 2 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Anemia | 16 Participants |
| Grade 2 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Metabolic | 3 Participants |
| Grade 2 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Gastrointestinal | 19 Participants |
| Grade 2 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Neutropenia | 2 Participants |
| Grade 2 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Neuropathy | 0 Participants |
| Grade 2 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Hepatobiliary | 0 Participants |
| Grade 2 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Infection | 0 Participants |
| Grade 2 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Coagulation | 0 Participants |
| Grade 2 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Hemorrhage | 0 Participants |
| Grade 2 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Ocular/Visual | 2 Participants |
| Grade 2 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Genitourinary/Renal | 1 Participants |
| Grade 2 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Cardiac | 2 Participants |
| Grade 2 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Sexual/Reproductive | 2 Participants |
| Grade 2 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Constitutional | 10 Participants |
| Grade 2 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Thrombocytopenia | 0 Participants |
| Grade 3 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Hemorrhage | 0 Participants |
| Grade 3 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Leukopenia | 0 Participants |
| Grade 3 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Thrombocytopenia | 0 Participants |
| Grade 3 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Neutropenia | 2 Participants |
| Grade 3 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Anemia | 4 Participants |
| Grade 3 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Auditory/Ear | 0 Participants |
| Grade 3 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Cardiac | 3 Participants |
| Grade 3 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Coagulation | 1 Participants |
| Grade 3 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Constitutional | 8 Participants |
| Grade 3 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Dermatologic | 5 Participants |
| Grade 3 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Gastrointestinal | 6 Participants |
| Grade 3 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Genitourinary/Renal | 1 Participants |
| Grade 3 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Hepatobiliary | 0 Participants |
| Grade 3 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Infection | 0 Participants |
| Grade 3 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Lymphatics | 4 Participants |
| Grade 3 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Metabolic | 6 Participants |
| Grade 3 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Neuropathy | 1 Participants |
| Grade 3 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Other Neurological | 3 Participants |
| Grade 3 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Ocular/Visual | 1 Participants |
| Grade 3 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Pain | 5 Participants |
| Grade 3 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Pulmonary | 3 Participants |
| Grade 3 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Sexual/Reproductive | 0 Participants |
| Grade 3 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Vascular | 0 Participants |
| Grade 4 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Hemorrhage | 0 Participants |
| Grade 4 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Sexual/Reproductive | 0 Participants |
| Grade 4 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Metabolic | 0 Participants |
| Grade 4 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Genitourinary/Renal | 0 Participants |
| Grade 4 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Gastrointestinal | 0 Participants |
| Grade 4 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Neuropathy | 0 Participants |
| Grade 4 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Dermatologic | 0 Participants |
| Grade 4 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Thrombocytopenia | 0 Participants |
| Grade 4 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Other Neurological | 0 Participants |
| Grade 4 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Constitutional | 0 Participants |
| Grade 4 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Coagulation | 0 Participants |
| Grade 4 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Ocular/Visual | 0 Participants |
| Grade 4 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Cardiac | 0 Participants |
| Grade 4 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Leukopenia | 0 Participants |
| Grade 4 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Pain | 0 Participants |
| Grade 4 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Auditory/Ear | 0 Participants |
| Grade 4 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Anemia | 1 Participants |
| Grade 4 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Pulmonary | 0 Participants |
| Grade 4 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Neutropenia | 0 Participants |
| Grade 4 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Infection | 1 Participants |
| Grade 4 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Hepatobiliary | 0 Participants |
| Grade 4 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Vascular | 0 Participants |
| Grade 4 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Lymphatics | 0 Participants |
| Grade 5 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Hemorrhage | 1 Participants |
| Grade 5 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Auditory/Ear | 0 Participants |
| Grade 5 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Thrombocytopenia | 0 Participants |
| Grade 5 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Metabolic | 0 Participants |
| Grade 5 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Infection | 0 Participants |
| Grade 5 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Gastrointestinal | 0 Participants |
| Grade 5 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Pain | 0 Participants |
| Grade 5 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Sexual/Reproductive | 0 Participants |
| Grade 5 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Genitourinary/Renal | 0 Participants |
| Grade 5 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Neuropathy | 0 Participants |
| Grade 5 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Dermatologic | 0 Participants |
| Grade 5 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Anemia | 0 Participants |
| Grade 5 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Constitutional | 0 Participants |
| Grade 5 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Hepatobiliary | 1 Participants |
| Grade 5 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Vascular | 0 Participants |
| Grade 5 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Other Neurological | 0 Participants |
| Grade 5 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Lymphatics | 0 Participants |
| Grade 5 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Coagulation | 0 Participants |
| Grade 5 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Pulmonary | 0 Participants |
| Grade 5 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Leukopenia | 0 Participants |
| Grade 5 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Neutropenia | 0 Participants |
| Grade 5 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Ocular/Visual | 0 Participants |
| Grade 5 (CTCAE v 3.0) | Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 | Cardiac | 0 Participants |
Secondary
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.
Time frame: 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.
Population: Eligible and treated patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Selumetinib) | Duration of Overall Survival | 8.5 months |
Secondary
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.
Time frame: Every other cycle for the first 6 months; then every 3 months thereafter for up to 5 years
Population: Eligible and treated patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Selumetinib) | Duration of Progression-free Survival | 2.3 months |
Other Pre-specified
Number of Participants Off Study Therapy for Each Reason Specified.
Time frame: from study entry until end of study treatment, up to 5 years.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Selumetinib) | Number of Participants Off Study Therapy for Each Reason Specified. | Disease progression | 32 participants |
| Treatment (Selumetinib) | Number of Participants Off Study Therapy for Each Reason Specified. | Refused further treatment | 5 participants |
| Treatment (Selumetinib) | Number of Participants Off Study Therapy for Each Reason Specified. | Toxicity as permitted | 6 participants |
| Treatment (Selumetinib) | Number of Participants Off Study Therapy for Each Reason Specified. | Death | 2 participants |
| Treatment (Selumetinib) | Number of Participants Off Study Therapy for Each Reason Specified. | Unspecified | 2 participants |
| Treatment (Selumetinib) | Number of Participants Off Study Therapy for Each Reason Specified. | Other - MD decision | 1 participants |
| Treatment (Selumetinib) | Number of Participants Off Study Therapy for Each Reason Specified. | Other - AZD6244 contraindicated w/Amiodarone | 1 participants |
| Treatment (Selumetinib) | Number of Participants Off Study Therapy for Each Reason Specified. | Other - PT never received any study drug | 1 participants |
Other Pre-specified
Patient Vital Status
Patients alive or dead after 24 months from time of study entry.
Time frame: Study entry up to 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Selumetinib) | Patient Vital Status | Alive, without disease progression | 7 participants |
| Treatment (Selumetinib) | Patient Vital Status | Alive, with disease progression | 4 participants |
| Treatment (Selumetinib) | Patient Vital Status | Dead, from disease | 37 participants |
| Treatment (Selumetinib) | Patient Vital Status | Dead, from undetermined cause | 1 participants |
| Treatment (Selumetinib) | Patient Vital Status | Dead, unspecified | 1 participants |