Selumetinib in Treating Patients With Recurrent or Persistent Endometrial Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01011933
• Collaborator: NRG Oncology (Other)
• Enrollment: 54
• Locations: 72
• Arm: 1
• Duration (Months): 76
• Patients Per Site: 0.8
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Recurrent Uterine Corpus Carcinoma	Other: Diagnostic Laboratory Biomarker Analysis; Drug: Selumetinib	Phase 2

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.

2. 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.

2. 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.

3. 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.

4. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Evaluation of AZD6244 (NSC #748727) in the Treatment of Recurrent or Persistent Endometrial Carcinoma
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Jan 1, 2016
• Actual Study Completion Date: Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
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.	Other: Diagnostic Laboratory Biomarker Analysis; Correlative studies; Drug: Selumetinib; Given PO; Other Names: ARRY-142886 AZD6244 MEK Inhibitor AZD6244

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 [Each cycle during treatment and 30 days after the last treatment.]

Secondary Outcome Measures

1. 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.

2. 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.

Other Outcome Measures

1. Number of Participants Off Study Therapy for Each Reason Specified. [from study entry until end of study treatment, up to 5 years.]

2. Patient Vital Status [Study entry up to 2 years]

   Patients alive or dead after 24 months from time of study entry.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Los Angeles County-USC Medical Center	Los Angeles	California	United States	90033
2	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
3	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado	United States	80045
4	Hartford Hospital	Hartford	Connecticut	United States	06102
5	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut	United States	06105
6	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06050
7	MedStar Washington Hospital Center	Washington	District of Columbia	United States	20010
8	Rush University Medical Center	Chicago	Illinois	United States	60612
9	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
10	Sudarshan K Sharma MD Limted-Gynecologic Oncology	Hinsdale	Illinois	United States	60521
11	Memorial Medical Center	Springfield	Illinois	United States	62781
12	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
13	Saint Vincent Oncology Center	Indianapolis	Indiana	United States	46260
14	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa	United States	50325
15	Mercy Cancer Center-West Lakes	Clive	Iowa	United States	50325
16	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
17	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa	United States	50309
18	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
19	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa	United States	50314
20	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
21	Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
22	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
23	Methodist West Hospital	West Des Moines	Iowa	United States	50266-7700
24	Mercy Medical Center-West Lakes	West Des Moines	Iowa	United States	50266
25	Menorah Medical Center	Overland Park	Kansas	United States	66209
26	Saint Luke's South Hospital	Overland Park	Kansas	United States	66213
27	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas	United States	66208
28	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland	United States	21237
29	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106-0995
30	Michigan Cancer Research Consortium CCOP	Ann Arbor	Michigan	United States	48106
31	Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48124
32	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
33	Hurley Medical Center	Flint	Michigan	United States	48502
34	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan	United States	48532
35	Allegiance Health	Jackson	Michigan	United States	49201
36	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
37	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
38	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
39	Sparrow Hospital	Lansing	Michigan	United States	48912
40	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
41	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
42	Saint Joseph Mercy Port Huron	Port Huron	Michigan	United States	48060
43	Saint Mary's of Michigan	Saginaw	Michigan	United States	48601
44	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
45	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
46	Truman Medical Center	Kansas City	Missouri	United States	64108
47	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
48	Saint Joseph Health Center	Kansas City	Missouri	United States	64114
49	North Kansas City Hospital	Kansas City	Missouri	United States	64116
50	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri	United States	64118
51	Research Medical Center	Kansas City	Missouri	United States	64132
52	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
53	Liberty Hospital	Liberty	Missouri	United States	64068
54	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
55	Saint Joseph Oncology Inc	Saint Joseph	Missouri	United States	64507
56	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
57	Cancer Research for the Ozarks NCORP	Springfield	Missouri	United States	65804
58	CoxHealth South Hospital	Springfield	Missouri	United States	65807
59	Women's Cancer Center of Nevada	Las Vegas	Nevada	United States	89169
60	State University of New York Downstate Medical Center	Brooklyn	New York	United States	11203
61	University of Cincinnati	Cincinnati	Ohio	United States	45267
62	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
63	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
64	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma	United States	74146
65	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
66	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania	United States	19010
67	Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301
68	Lankenau Medical Center	Wynnewood	Pennsylvania	United States	19096
69	Main Line Health NCORP	Wynnewood	Pennsylvania	United States	19096
70	Women and Infants Hospital	Providence	Rhode Island	United States	02905
71	Lyndon Baines Johnson General Hospital	Houston	Texas	United States	77026-1967
72	M D Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• National Cancer Institute (NCI)
• NRG Oncology

Investigators

• Principal Investigator: Robert Coleman, NRG Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01011933
• Other Study ID Numbers: NCI-2011-01958; NCI-2011-01958; GOG-0229H; CDR0000651456; GOG-0229H; GOG-0229H; U10CA180868; U10CA027469
• First Posted: Nov 11, 2009
• Last Update Posted: Jul 23, 2019
• Last Verified: Jul 1, 2019

• Additional relevant MeSH terms: Carcinoma; Adenocarcinoma; Adenocarcinoma, Clear Cell; Carcinoma, Adenosquamous; Recurrence

Study Results

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.

Arm/Group Title	Treatment (Selumetinib)
Arm/Group Description	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.
Period Title: Overall Study
STARTED	54
COMPLETED	50
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Treatment (Selumetinib)
Arm/Group Description	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.
Overall Participants	50
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.8 (9.7)
Age, Customized (participants) [Number]
40-49 years	4 8%
50-59 years	15 30%
60-69 years	18 36%
70-79 years	11 22%
80-89 years	2 4%
Sex: Female, Male (Count of Participants)
Female	50 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	50 100%
Cell Type (participants) [Number]
Clear cell carcinoma	1 2%
Endometrioid adenocarcinoma	31 62%
Mixed epithelial carcinoma	10 20%
Serous adenocarcinoma	8 16%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Selumetinib)
Arm/Group Description	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.
Measure Participants	50
without progression-free survival	39 78%
with progression-free survival	11 22%

2. Primary Outcome

Title	Objective Tumor Response Rate Assessed by RECIST
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Selumetinib)
Arm/Group Description	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.
Measure Participants	50
Complete Response	1 2%
Increase Disease	23 46%
Partial Response	2 4%
Stable Disease	13 26%
Indeterminate	11 22%

3. Primary Outcome

Title	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.

Outcome Measure Data

Analysis Population Description

Eligible and evaluable patients

Arm/Group Title	Grade 0	Grade 1 (CTCAE v 3.0)	Grade 2 (CTCAE v 3.0)	Grade 3 (CTCAE v 3.0)	Grade 4 (CTCAE v 3.0)	Grade 5 (CTCAE v 3.0)
Arm/Group Description	Number of patients who did not experience the specified AE.	Number of patients who experienced a grade 1 event using Common Terminology Criteria version 3.0	Number of patients who experienced a grade 2 event using Common Terminology Criteria version 3.0	Number of patients who experienced a grade 3 event using Common Terminology Criteria version 3.0	Number of patients who experienced a grade 4 event using Common Terminology Criteria version 3.0	Number of patients who experienced a grade 5 event using Common Terminology Criteria version 3.0
Measure Participants	52	52	52	52	52	52
Leukopenia	39 78%	11 NaN	2 NaN	0 NaN	0 NaN	0 NaN
Thrombocytopenia	48 96%	4 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Neutropenia	45 90%	3 NaN	2 NaN	2 NaN	0 NaN	0 NaN
Anemia	21 42%	10 NaN	16 NaN	4 NaN	1 NaN	0 NaN
Auditory/Ear	51 102%	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Cardiac	45 90%	2 NaN	2 NaN	3 NaN	0 NaN	0 NaN
Coagulation	51 102%	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN
Constitutional	16 32%	18 NaN	10 NaN	8 NaN	0 NaN	0 NaN
Dermatologic	16 32%	13 NaN	18 NaN	5 NaN	0 NaN	0 NaN
Gastrointestinal	9 18%	18 NaN	19 NaN	6 NaN	0 NaN	0 NaN
Genitourinary/Renal	50 100%	0 NaN	1 NaN	1 NaN	0 NaN	0 NaN
Hemorrhage	47 94%	4 NaN	0 NaN	0 NaN	0 NaN	1 NaN
Hepatobiliary	51 102%	0 NaN	0 NaN	0 NaN	0 NaN	1 NaN
Infection	51 102%	0 NaN	0 NaN	0 NaN	1 NaN	0 NaN
Lymphatics	31 62%	10 NaN	7 NaN	4 NaN	0 NaN	0 NaN
Metabolic	34 68%	9 NaN	3 NaN	6 NaN	0 NaN	0 NaN
Neuropathy	49 98%	2 NaN	0 NaN	1 NaN	0 NaN	0 NaN
Other Neurological	44 88%	5 NaN	0 NaN	3 NaN	0 NaN	0 NaN
Ocular/Visual	48 96%	1 NaN	2 NaN	1 NaN	0 NaN	0 NaN
Pain	33 66%	8 NaN	6 NaN	5 NaN	0 NaN	0 NaN
Pulmonary	40 80%	6 NaN	3 NaN	3 NaN	0 NaN	0 NaN
Sexual/Reproductive	51 102%	0 NaN	2 NaN	0 NaN	0 NaN	0 NaN
Vascular	51 102%	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN

4. Secondary Outcome

Title	Duration of Progression-free Survival
Description	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

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Treatment (Selumetinib)
Arm/Group Description	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.
Measure Participants	52
Median (Inter-Quartile Range) [months]	2.3

5. Secondary Outcome

Title	Duration of Overall Survival
Description	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.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Treatment (Selumetinib)
Arm/Group Description	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.
Measure Participants	52
Median (Inter-Quartile Range) [months]	8.5

6. Other Pre-specified Outcome

Title	Number of Participants Off Study Therapy for Each Reason Specified.
Time Frame	from study entry until end of study treatment, up to 5 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Selumetinib)
Arm/Group Description	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.
Measure Participants	50
Disease progression	32 64%
Refused further treatment	5 10%
Toxicity as permitted	6 12%
Death	2 4%
Unspecified	2 4%
Other - MD decision	1 2%
Other - AZD6244 contraindicated w/Amiodarone	1 2%
Other - PT never received any study drug	1 2%

7. Other Pre-specified Outcome

Title	Patient Vital Status
Description	Patients alive or dead after 24 months from time of study entry.
Time Frame	Study entry up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Selumetinib)
Arm/Group Description	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.
Measure Participants	50
Alive, without disease progression	7 14%
Alive, with disease progression	4 8%
Dead, from disease	37 74%
Dead, from undetermined cause	1 2%
Dead, unspecified	1 2%

Adverse Events

Time Frame	Adverse Events(AEs) are reported up to 30 days after last treatment. Late AEs can be reported up to 5 years after patient enrollment.
Arm/Group Title	Treatment (Selumetinib)
Arm/Group Description	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.
All Cause Mortality
	Treatment (Selumetinib)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Selumetinib)
	Affected / at Risk (%)	# Events
Total	32/50 (64%)
Blood and lymphatic system disorders
Leukocytes	1/50 (2%)
Hemoglobin	1/50 (2%)
Edema: Limb	1/50 (2%)
Cardiac disorders
S/N Arrhythmia: Atrial Fibrillation	1/50 (2%)
Hypotension	2/50 (4%)
Eye disorders
Ocular/Visual - Other	1/50 (2%)
Gastrointestinal disorders
Dysphagia	1/50 (2%)
Mucositis (Functional/Sympt) - Oral Cavity	2/50 (4%)
Obstruction, Gi - Small Bowel Nos	1/50 (2%)
Dehydration	1/50 (2%)
Constipation	1/50 (2%)
General disorders
Death No Ctcae Term - Disease Progression Nos	3/50 (6%)
Death No Ctcae Term - Death Nos	1/50 (2%)
Pain: Chest /Thorax Nos	1/50 (2%)
Pain: Abdominal Pain Nos	1/50 (2%)
Hepatobiliary disorders
Liver Dysfunction	1/50 (2%)
Infections and infestations
Inf Unknown Anc: Skin (Cellulitis)	1/50 (2%)
Metabolism and nutrition disorders
Hyponatremia	1/50 (2%)
Nervous system disorders
Dizziness	1/50 (2%)
Neuropathy-Sensory	1/50 (2%)
Renal and urinary disorders
Obstruction, Gu - Ureter	1/50 (2%)
Reproductive system and breast disorders
Vaginitis	1/50 (2%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	3/50 (6%)
Skin and subcutaneous tissue disorders
Rash	1/50 (2%)
Vascular disorders
Hemorrhage, Gi - Rectum	1/50 (2%)
Thrombosis/Thrombus/Embolism	5/50 (10%)
Other (Not Including Serious) Adverse Events
	Treatment (Selumetinib)
	Affected / at Risk (%)	# Events
Total	38/50 (76%)
Blood and lymphatic system disorders
Neutrophils	8/50 (16%)
Platelets	7/50 (14%)
Leukocytes	13/50 (26%)
Hemoglobin	35/50 (70%)
Edema: Trunk/Genital	3/50 (6%)
Edema: Limb	23/50 (46%)
Edema: Head And Neck	6/50 (12%)
Cardiac disorders
Hypotension	3/50 (6%)
Eye disorders
Blurred Vision	5/50 (10%)
Gastrointestinal disorders
Flatulence	3/50 (6%)
Heartburn	3/50 (6%)
Taste Alteration	4/50 (8%)
Dry Mouth	4/50 (8%)
Mucositis (Clinical Exam) - Oral Cavity	3/50 (6%)
Vomiting	21/50 (42%)
Anorexia	11/50 (22%)
Constipation	16/50 (32%)
Nausea	34/50 (68%)
Diarrhea	29/50 (58%)
General disorders
Weight Gain	5/50 (10%)
Fever	7/50 (14%)
Rigors/Chills	3/50 (6%)
Fatigue	38/50 (76%)
Insomnia	3/50 (6%)
Pain: Extremity-Limb	6/50 (12%)
Pain: Back	8/50 (16%)
Pain: Joint	6/50 (12%)
Pain: Abdominal Pain Nos	14/50 (28%)
Infections and infestations
Inf W/Nml Or Gr 1 Or 2 Anc: Urinary Tract Nos	4/50 (8%)
Metabolism and nutrition disorders
Ast	10/50 (20%)
Creatinine	4/50 (8%)
Hypoalbuminemia	10/50 (20%)
Alt	7/50 (14%)
Alkaline Phosphatase	9/50 (18%)
Hypophosphatemia	4/50 (8%)
Hyponatremia	6/50 (12%)
Hypocalcemia	8/50 (16%)
Hyperkalemia	3/50 (6%)
Hyperglycemia	9/50 (18%)
Hypokalemia	4/50 (8%)
Hypoglycemia	3/50 (6%)
Hypomagnesemia	7/50 (14%)
Nervous system disorders
Mood Alteration - Depression	6/50 (12%)
Mood Alteration - Anxiety	3/50 (6%)
Dizziness	3/50 (6%)
Neuropathy-Sensory	8/50 (16%)
Respiratory, thoracic and mediastinal disorders
Cough	10/50 (20%)
Dyspnea	13/50 (26%)
Skin and subcutaneous tissue disorders
Acne	15/50 (30%)
Rash	24/50 (48%)
Dry Skin	10/50 (20%)
Pruritus	3/50 (6%)
Vascular disorders
Ptt	3/50 (6%)
Hemorrhage/Pulmonary - Nose	4/50 (8%)
Thrombosis/Thrombus/Embolism	6/50 (12%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.