Selumetinib With or Without Temsirolimus in Treating Patients With Metastatic, Recurrent, or Locally Advanced Soft Tissue Sarcoma That Cannot Be Removed By Surgery

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT01206140
Collaborator
National Comprehensive Cancer Network (Other)
70
8
2
54
8.8
0.2

Study Details

Study Description

Brief Summary

This randomized phase II trial is studying how well giving selumetinib together with or without temsirolimus works in treating patients with metastatic, recurrent, or locally advanced soft tissue sarcoma that cannot be removed by surgery. Selumetinib and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving selumetinib together with temsirolimus is more effective than giving selumetinib alone.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. Compare the progression-free survival of the MEK inhibitor, AZD6244 (selumetinib) alone, and the combination of AZD6244 and a mammalian target of rapamycin inhibitor (mTORi), temsirolimus (CCI-779) in patients with recurrent metastatic or recurrent locally unresectable soft-tissue sarcomas.
SECONDARY OBJECTIVES:
  1. Determine the rates of apoptosis, autophagy, and proliferation with AZD6244 alone, and in combination with temsirolimus by immunohistochemistry in tumor and surrogate skin tissue biopsies. (exploratory) II. Assess the activation status of protein kinase B (Akt), 5E-BP1, eukaryotic translation initiation factor 4 gamma, 1 (eIF-4G), and ribosomal protein S6 kinase (S6K) in tumor biopsy samples and surrogate skin tissue biopsy samples.(exploratory) III. Assess inhibition of activated mitogen-activated protein kinase 1/2 (ERK1/2) in stimulated peripheral blood mononuclear cells. (exploratory) IV. Assess response by Choi criteria. V. Compare the response rate and 4-month progression-free survival (PFS) rate in patients treated with these regimens.

  2. Compare the response rate, 4-month PFS rate and toxicity of AZD6244 alone and in combination with temsirolimus.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive selumetinib orally (PO) twice daily on days 1-28 and temsirolimus intravenously (IV) over 30-60 minutes on days 1, 8, 15, and 22.

ARM II: Patients receive selumetinib as in arm I. Patients who experience disease progression may cross over to arm I.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up for 30 days.

Study Design

Study Type:
Interventional
Actual Enrollment :
70 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Randomized, Phase II Trial of AZD6244 Alone and AZD6244 Plus Temsirolimus for Soft-Tissue Sarcomas
Study Start Date :
Oct 1, 2010
Actual Primary Completion Date :
Apr 1, 2015
Actual Study Completion Date :
Apr 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm I (selumetinib and temsirolimus)

Patients receive selumetinib PO twice daily on days 1-28 and temsirolimus IV over 30-60 minutes on days 1, 8, 15, and 22.

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Selumetinib
Given PO
Other Names:
  • ARRY-142886
  • AZD6244
  • MEK Inhibitor AZD6244
  • Drug: Temsirolimus
    Given IV
    Other Names:
  • CCI-779
  • CCI-779 Rapamycin Analog
  • Cell Cycle Inhibitor 779
  • Rapamycin Analog
  • Rapamycin Analog CCI-779
  • Torisel
  • Experimental: Arm II (selumetinib)

    Patients receive selumetinib as in arm I. Patients who experience disease progression may cross over to arm I.

    Other: Laboratory Biomarker Analysis
    Correlative studies

    Drug: Selumetinib
    Given PO
    Other Names:
  • ARRY-142886
  • AZD6244
  • MEK Inhibitor AZD6244
  • Outcome Measures

    Primary Outcome Measures

    1. Progression-free Survival [Until disease progression or death, up to 4.5 years]

      Progression-free survival was estimated using the product-limit method of Kaplan and Meier. Progression wasl evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions, or death.

    Secondary Outcome Measures

    1. Number of Participants With Objective Response [Evaluated for response after every two cycles, up to 4.5 years.]

      Response evaluated using the Choi criteria. CR - disappearance of all lesions and no new lesions; PR - a decrease in size (the sum of longest diameters of target lesions as defined in RECIST) of 10% or more or a decrease in tumor density (HU) of 15% or more on CT and no new lesions and no obvious progression of nonmeasurable disease; SD - does not meet the criteria for CR, PR, or PD and no symptomatic deterioration attributed to tumor progression; PD - an increase in tumor size of 10% or more and does not meet criteria of PR by tumor density (HU) on CT or new lesions or new intratumoral nodules or increase in the size of the existing intratumoral nodules. Objective response = CR+PR.

    2. 4 -Month Progression-free Survival Rate. [Four months]

      Progression-free survival rate was calculated using the survival distribution function, and 95% confidence limits were calculated using the log-log transformation. Progression was defined using the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions, or death.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients must have had histologic verification of soft-tissue sarcoma at original diagnosis (GIST subtype is eligible)

    • Patients must have metastatic (de novo or recurrent) or locally advanced, unresectable disease; patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan

    • ECOG 0-2 (Karnofsky >= 50%)

    • Patients may have received 0-2 prior cytotoxic chemotherapeutic regimens for metastatic or recurrent disease (single-agent or combination chemotherapies)

    • Estimated life expectancy > 12 weeks

    • Peripheral absolute neutrophil count (ANC) >= 1000/uL

    • Platelet count >= 100,000/uL (transfusion independent)

    • Hemoglobin >= 8.0 gm/dL (may receive RBC transfusions)

    • Creatinine =< 1.5 x upper institutional limits of normal, or calculated creatinine clearance >= 45mL/min, based on the Cockcroft-Gault formula

    • Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age

    • SGPT (ALT) =< 5 x upper limit of normal (ULN) for age

    • No evidence of dyspnea at rest, no exercise intolerance

    • Pulse oximetry > 94% if there is clinical indication for determination

    • For women: must be surgically sterile, postmenopausal, or compliant with a medically approved contraceptive regimen (for example, intrauterine device [IUD], birth control pills, or barrier device) during and until 4 weeks after the last dose of study treatment; must have a negative serum or urine pregnancy test within 7 days before study enrollment, and must not be breast-feeding; should a woman become pregnant or suspect she is pregnant while she or her partner participating in this study, the patient should inform her treating physician immediately; for men: must be surgically sterile or compliant with a contraceptive regimen during and for 16 weeks after the treatment period; please note that the AZD6244 manufacturer recommends that adequate contraception for male patients should be used for 16 weeks post-last dose due to sperm life cycle

    • All patients must sign a written informed consent

    Exclusion Criteria:
    • Patients with pediatric-type sarcomas (Ewing's or primitive neuroectodermal tumor, rhabdomyosarcoma, and desmoplastic small round cell tumor)

    • Concomitant Medications

    • Growth factor(s): growth factors that support platelet or white cell number or function must not have been administered within the past 7 days

    • Steroids: patients with CNS tumors who have not been on a stable or decreasing dose of dexamethasone for the past 7 days

    • Investigational Drugs: patients who are currently receiving another investigational drug

    • Anti-cancer Agents: patients who are currently receiving other anti-cancer agents; at least 3 weeks must have elapsed since prior chemotherapy or radiation (6 weeks for mitomycin-C and nitrosureas)

    • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events

    • History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD6244

    • Previous MEK inhibitor use

    • Patients with QTc interval > 450 msecs or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome); this may be determined by either Bazett's correction (QTc =QT/RR0.5) or Friderica's correction (QTc = QT/RR0.33); QTc exclusion > 450 msec requires calculation according to both formulas

    • Patients unable to swallow the AZD6244 capsules are ineligible

    • Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption

    • Uncontrolled intercurrent illness including, but not limited to, uncontrolled, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements

    • Pregnant women are excluded from this study because the effects of AZD6244 on the developing human fetus at the recommended therapeutic dose are unknown; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated with AZD6244

    • HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD6244; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated

    • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study

    • Prior cardiac history of uncontrolled hypertension, New York Heart Association (NYHA) Classification >= class II, current or prior cardiomyopathy, baseline LVEF < 50%, ongoing atrial fibrillation, recent myocardial infarction or unstable ischemic heart disease

    • Concomitant Strong CYP1A2 or CYP3A4 inducers and/or inhibitors; prior treatment with an mTOR inhibitor for recurrent soft-tissue sarcoma

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Tower Cancer Research Foundation Beverly Hills California United States 90211-1850
    2 City of Hope Comprehensive Cancer Center Duarte California United States 91010
    3 USC / Norris Comprehensive Cancer Center Los Angeles California United States 90033
    4 University of California Davis Comprehensive Cancer Center Sacramento California United States 95817
    5 University of California Davis Phase 2 Consortium Sacramento California United States 95817
    6 Penn State Milton S Hershey Medical Center Hershey Pennsylvania United States 17033-0850
    7 University of Pittsburgh Cancer Institute Pittsburgh Pennsylvania United States 15232
    8 University of Pittsburgh Pittsburgh Pennsylvania United States 15232

    Sponsors and Collaborators

    • National Cancer Institute (NCI)
    • National Comprehensive Cancer Network

    Investigators

    • Principal Investigator: Warren Chow, City of Hope Comprehensive Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01206140
    Other Study ID Numbers:
    • NCI-2011-02532
    • NCI-2011-02532
    • CDR0000685408
    • CHNMC-PHII-95
    • NCCN-T06
    • PHII-95
    • 8412
    • N01CM00038
    • P30CA033572
    First Posted:
    Sep 21, 2010
    Last Update Posted:
    Oct 5, 2015
    Last Verified:
    Jan 1, 2015
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Arm I (Selumetinib) Arm II (Selumetinib and Temsirolimus)
    Arm/Group Description Patients receive 75 mg selumetinib as in arm II. Patients who experience disease progression may cross over to arm II. Laboratory Biomarker Analysis: Correlative studies Selumetinib: Given PO Patients receive selumetinib 75 mg PO twice daily on days 1-28 and temsirolimus 25 mg IV over 30-60 minutes on days 1, 8, 15, and 22. Laboratory Biomarker Analysis: Correlative studies Selumetinib: Given PO Temsirolimus: Given IV
    Period Title: Overall Study
    STARTED 35 35
    COMPLETED 34 35
    NOT COMPLETED 1 0

    Baseline Characteristics

    Arm/Group Title Arm I (Selumetinib) Arm II (Selumetinib and Temsirolimus) Total
    Arm/Group Description Patients receive 75 mg selumetinib as in arm II. Patients who experience disease progression may cross over to arm II. Laboratory Biomarker Analysis: Correlative studies Selumetinib: Given PO Patients receive selumetinib 75 mg PO twice daily on days 1-28 and temsirolimus 25 mg IV over 30-60 minutes on days 1, 8, 15, and 22. Laboratory Biomarker Analysis: Correlative studies Selumetinib: Given PO Temsirolimus: Given IV Total of all reporting groups
    Overall Participants 34 35 69
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    56
    56
    56
    Sex: Female, Male (Count of Participants)
    Female
    17
    50%
    25
    71.4%
    42
    60.9%
    Male
    17
    50%
    10
    28.6%
    27
    39.1%
    Region of Enrollment (participants) [Number]
    United States
    34
    100%
    35
    100%
    69
    100%

    Outcome Measures

    1. Primary Outcome
    Title Progression-free Survival
    Description Progression-free survival was estimated using the product-limit method of Kaplan and Meier. Progression wasl evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions, or death.
    Time Frame Until disease progression or death, up to 4.5 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I (Selumetinib) Arm II (Selumetinib and Temsirolimus)
    Arm/Group Description Patients receive 75 mg selumetinib as in arm II. Patients who experience disease progression may cross over to arm II. Laboratory Biomarker Analysis: Correlative studies Selumetinib: Given PO Patients receive selumetinib 75 mg PO twice daily on days 1-28 and temsirolimus 25 mg IV over 30-60 minutes on days 1, 8, 15, and 22. Laboratory Biomarker Analysis: Correlative studies Selumetinib: Given PO Temsirolimus: Given IV
    Measure Participants 34 35
    Median (95% Confidence Interval) [months]
    1.8
    3.7
    2. Secondary Outcome
    Title Number of Participants With Objective Response
    Description Response evaluated using the Choi criteria. CR - disappearance of all lesions and no new lesions; PR - a decrease in size (the sum of longest diameters of target lesions as defined in RECIST) of 10% or more or a decrease in tumor density (HU) of 15% or more on CT and no new lesions and no obvious progression of nonmeasurable disease; SD - does not meet the criteria for CR, PR, or PD and no symptomatic deterioration attributed to tumor progression; PD - an increase in tumor size of 10% or more and does not meet criteria of PR by tumor density (HU) on CT or new lesions or new intratumoral nodules or increase in the size of the existing intratumoral nodules. Objective response = CR+PR.
    Time Frame Evaluated for response after every two cycles, up to 4.5 years.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I (Selumetinib) Arm II (Selumetinib and Temsirolimus)
    Arm/Group Description Patients receive 75 mg selumetinib as in arm II. Patients who experience disease progression may cross over to arm II. Laboratory Biomarker Analysis: Correlative studies Selumetinib: Given PO Patients receive selumetinib 75 mg PO twice daily on days 1-28 and temsirolimus 25 mg IV over 30-60 minutes on days 1, 8, 15, and 22. Laboratory Biomarker Analysis: Correlative studies Selumetinib: Given PO Temsirolimus: Given IV
    Measure Participants 34 35
    Number [participants]
    5
    14.7%
    4
    11.4%
    3. Secondary Outcome
    Title 4 -Month Progression-free Survival Rate.
    Description Progression-free survival rate was calculated using the survival distribution function, and 95% confidence limits were calculated using the log-log transformation. Progression was defined using the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions, or death.
    Time Frame Four months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I (Selumetinib) Arm II (Selumetinib and Temsirolimus)
    Arm/Group Description Patients receive 75 mg selumetinib as in arm II. Patients who experience disease progression may cross over to arm II. Laboratory Biomarker Analysis: Correlative studies Selumetinib: Given PO Patients receive selumetinib 75 mg PO twice daily on days 1-28 and temsirolimus 25 mg IV over 30-60 minutes on days 1, 8, 15, and 22. Laboratory Biomarker Analysis: Correlative studies Selumetinib: Given PO Temsirolimus: Given IV
    Measure Participants 34 35
    Number (95% Confidence Interval) [percent of participants]
    24
    70.6%
    24
    68.6%

    Adverse Events

    Time Frame Adverse events collected over a period of 28 months
    Adverse Event Reporting Description "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
    Arm/Group Title Arm I (Selumetinib) Arm II (Selumetinib and Temsirolimus)
    Arm/Group Description Patients receive 75 mg selumetinib as in arm II. Patients who experience disease progression may cross over to arm II. Laboratory Biomarker Analysis: Correlative studies Selumetinib: Given PO Patients receive selumetinib 75 mg PO twice daily on days 1-28 and temsirolimus 25 mg IV over 30-60 minutes on days 1, 8, 15, and 22. Laboratory Biomarker Analysis: Correlative studies Selumetinib: Given PO Temsirolimus: Given IV
    All Cause Mortality
    Arm I (Selumetinib) Arm II (Selumetinib and Temsirolimus)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Arm I (Selumetinib) Arm II (Selumetinib and Temsirolimus)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 23/34 (67.6%) 18/35 (51.4%)
    Blood and lymphatic system disorders
    Anemia 3/34 (8.8%) 5 1/35 (2.9%) 1
    Cardiac disorders
    Aortic valve disease 0/34 (0%) 0 1/35 (2.9%) 1
    Atrial fibrillation 1/34 (2.9%) 1 0/35 (0%) 0
    Atrial flutter 1/34 (2.9%) 1 0/35 (0%) 0
    Cardiac arrest 0/34 (0%) 0 1/35 (2.9%) 1
    Sinus tachycardia 1/34 (2.9%) 1 0/35 (0%) 0
    Volume overload 0/34 (0%) 0 1/35 (2.9%) 1
    Eye disorders
    Conjunctivitis 1/34 (2.9%) 1 0/35 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 4/34 (11.8%) 5 1/35 (2.9%) 1
    Bloating 0/34 (0%) 0 1/35 (2.9%) 1
    Colitis 1/34 (2.9%) 1 0/35 (0%) 0
    Diarrhea 2/34 (5.9%) 3 0/35 (0%) 0
    Duodenal fistula 0/34 (0%) 0 1/35 (2.9%) 1
    Duodenal hemorrhage 1/34 (2.9%) 1 0/35 (0%) 0
    Duodenal obstruction 2/34 (5.9%) 3 0/35 (0%) 0
    Dyspepsia 0/34 (0%) 0 1/35 (2.9%) 1
    Dysphagia 1/34 (2.9%) 1 1/35 (2.9%) 1
    Esophagitis 1/34 (2.9%) 1 0/35 (0%) 0
    Gastric hemorrhage 1/34 (2.9%) 1 0/35 (0%) 0
    Gastric ulcer 1/34 (2.9%) 1 0/35 (0%) 0
    Gastritis 0/34 (0%) 0 1/35 (2.9%) 1
    Ileus 1/34 (2.9%) 1 0/35 (0%) 0
    Mucositis oral 1/34 (2.9%) 1 2/35 (5.7%) 2
    Nausea 3/34 (8.8%) 3 2/35 (5.7%) 2
    Oral pain 1/34 (2.9%) 1 1/35 (2.9%) 1
    Rectal hemorrhage 1/34 (2.9%) 1 0/35 (0%) 0
    Small intestinal obstruction 0/34 (0%) 0 1/35 (2.9%) 1
    Upper gastrointestinal hemorrhage 1/34 (2.9%) 1 0/35 (0%) 0
    Vomiting 2/34 (5.9%) 2 2/35 (5.7%) 2
    General disorders
    Chills 1/34 (2.9%) 1 0/35 (0%) 0
    Edema face 0/34 (0%) 0 1/35 (2.9%) 1
    Fatigue 3/34 (8.8%) 3 0/35 (0%) 0
    Fever 2/34 (5.9%) 4 1/35 (2.9%) 1
    Injection site reaction 2/34 (5.9%) 2 0/35 (0%) 0
    Malaise 1/34 (2.9%) 1 0/35 (0%) 0
    Non-cardiac chest pain 1/34 (2.9%) 1 0/35 (0%) 0
    Pain 1/34 (2.9%) 1 0/35 (0%) 0
    vaginal mucositis 0/34 (0%) 0 1/35 (2.9%) 1
    Infections and infestations
    Biliary tract infection 1/34 (2.9%) 1 0/35 (0%) 0
    Bladder infection 0/34 (0%) 0 1/35 (2.9%) 1
    Bronchial infection 1/34 (2.9%) 1 0/35 (0%) 0
    Catheter related infection 1/34 (2.9%) 2 1/35 (2.9%) 1
    Device related infection 2/34 (5.9%) 2 1/35 (2.9%) 1
    Endocarditis infective 0/34 (0%) 0 1/35 (2.9%) 1
    Lung infection 3/34 (8.8%) 3 1/35 (2.9%) 1
    Paronychia 3/34 (8.8%) 4 1/35 (2.9%) 1
    Penile infection 1/34 (2.9%) 1 0/35 (0%) 0
    Sepsis 2/34 (5.9%) 3 0/35 (0%) 0
    Skin infection 0/34 (0%) 0 1/35 (2.9%) 1
    Unknown source but positive blood cultur 1/34 (2.9%) 1 0/35 (0%) 0
    Urinary tract infection 1/34 (2.9%) 1 0/35 (0%) 0
    Viral gastroenteritis 0/34 (0%) 0 1/35 (2.9%) 1
    left groin area 1/34 (2.9%) 1 0/35 (0%) 0
    Injury, poisoning and procedural complications
    Hip fracture 2/34 (5.9%) 2 0/35 (0%) 0
    Investigations
    Alkaline phosphatase increased 2/34 (5.9%) 3 0/35 (0%) 0
    Creatinine increased 0/34 (0%) 0 1/35 (2.9%) 1
    Ejection fraction decreased 0/34 (0%) 0 1/35 (2.9%) 1
    Lymphocyte count decreased 4/34 (11.8%) 5 0/35 (0%) 0
    Neutrophil count decreased 1/34 (2.9%) 1 0/35 (0%) 0
    Platelet count decreased 1/34 (2.9%) 1 0/35 (0%) 0
    Weight gain 1/34 (2.9%) 1 0/35 (0%) 0
    Weight loss 1/34 (2.9%) 1 0/35 (0%) 0
    White blood cell decreased 1/34 (2.9%) 1 1/35 (2.9%) 1
    Metabolism and nutrition disorders
    Dehydration 4/34 (11.8%) 5 4/35 (11.4%) 4
    Hypoalbuminemia 1/34 (2.9%) 5 2/35 (5.7%) 2
    Hypokalemia 4/34 (11.8%) 4 0/35 (0%) 0
    Hypomagnesemia 1/34 (2.9%) 1 0/35 (0%) 0
    Hyponatremia 1/34 (2.9%) 1 1/35 (2.9%) 1
    Hypophosphatemia 2/34 (5.9%) 3 0/35 (0%) 0
    Musculoskeletal and connective tissue disorders
    Back pain 1/34 (2.9%) 1 0/35 (0%) 0
    Chest wall pain 0/34 (0%) 0 1/35 (2.9%) 1
    Generalized muscle weakness 2/34 (5.9%) 4 1/35 (2.9%) 1
    Myalgia 1/34 (2.9%) 1 0/35 (0%) 0
    Neck pain 1/34 (2.9%) 1 0/35 (0%) 0
    Pain in extremity 2/34 (5.9%) 2 0/35 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Progressive disease 1/34 (2.9%) 1 0/35 (0%) 0
    Nervous system disorders
    Depressed level of consciousness 2/34 (5.9%) 2 0/35 (0%) 0
    Paresthesia 0/34 (0%) 0 1/35 (2.9%) 1
    Syncope 1/34 (2.9%) 1 1/35 (2.9%) 1
    Psychiatric disorders
    Anxiety 1/34 (2.9%) 1 0/35 (0%) 0
    Confusion 1/34 (2.9%) 1 0/35 (0%) 0
    Renal and urinary disorders
    Hematuria 1/34 (2.9%) 1 0/35 (0%) 0
    Urinary frequency 1/34 (2.9%) 1 0/35 (0%) 0
    Urinary tract pain 1/34 (2.9%) 1 0/35 (0%) 0
    Reproductive system and breast disorders
    Genital edema 1/34 (2.9%) 1 0/35 (0%) 0
    Vaginal hemorrhage 1/34 (2.9%) 1 0/35 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Bronchopulmonary hemorrhage 1/34 (2.9%) 1 0/35 (0%) 0
    Dyspnea 2/34 (5.9%) 2 0/35 (0%) 0
    Hypoxia 1/34 (2.9%) 1 0/35 (0%) 0
    Pleural effusion 1/34 (2.9%) 1 1/35 (2.9%) 1
    Pneumothorax 1/34 (2.9%) 1 0/35 (0%) 0
    Respiratory failure 2/34 (5.9%) 2 0/35 (0%) 0
    Skin and subcutaneous tissue disorders
    Pruritus 1/34 (2.9%) 1 0/35 (0%) 0
    Rash maculo-papular 1/34 (2.9%) 1 0/35 (0%) 0
    Skin ulceration 1/34 (2.9%) 1 0/35 (0%) 0
    Surgical and medical procedures
    Spinal cord compression 1/34 (2.9%) 1 0/35 (0%) 0
    T5 Laminectomy 0/34 (0%) 0 1/35 (2.9%) 1
    Vascular disorders
    Hypertension 6/34 (17.6%) 18 1/35 (2.9%) 1
    Hypotension 3/34 (8.8%) 3 0/35 (0%) 0
    Lymphedema 2/34 (5.9%) 2 1/35 (2.9%) 1
    Thromboembolic event 1/34 (2.9%) 1 1/35 (2.9%) 1
    Other (Not Including Serious) Adverse Events
    Arm I (Selumetinib) Arm II (Selumetinib and Temsirolimus)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 33/34 (97.1%) 35/35 (100%)
    Blood and lymphatic system disorders
    Anemia 25/34 (73.5%) 98 27/35 (77.1%) 73
    Cardiac disorders
    Atrial fibrillation 1/34 (2.9%) 1 0/35 (0%) 0
    Atrioventricular block first degree 0/34 (0%) 0 1/35 (2.9%) 2
    Murmer 0/34 (0%) 0 1/35 (2.9%) 1
    Palpitations 2/34 (5.9%) 2 0/35 (0%) 0
    Pericardial effusion 0/34 (0%) 0 2/35 (5.7%) 2
    Sinus bradycardia 1/34 (2.9%) 3 0/35 (0%) 0
    Sinus tachycardia 7/34 (20.6%) 14 5/35 (14.3%) 5
    pedal edema 1/34 (2.9%) 1 0/35 (0%) 0
    Ear and labyrinth disorders
    Ear pain 0/34 (0%) 0 2/35 (5.7%) 3
    Middle ear inflammation 1/34 (2.9%) 1 0/35 (0%) 0
    Tinnitus 1/34 (2.9%) 1 1/35 (2.9%) 1
    Endocrine disorders
    Cushingoid 1/34 (2.9%) 1 0/35 (0%) 0
    Hyperthyroidism 0/34 (0%) 0 1/35 (2.9%) 1
    Eye disorders
    Blepharitis 1/34 (2.9%) 1 0/35 (0%) 0
    Blurred vision 2/34 (5.9%) 2 0/35 (0%) 0
    Cataract 1/34 (2.9%) 1 1/35 (2.9%) 1
    Conjunctivitis 1/34 (2.9%) 2 3/35 (8.6%) 3
    Dry eye 0/34 (0%) 0 1/35 (2.9%) 1
    Eye pain 1/34 (2.9%) 1 3/35 (8.6%) 6
    Floaters 2/34 (5.9%) 2 1/35 (2.9%) 1
    Photophobia 0/34 (0%) 0 1/35 (2.9%) 1
    Scleral disorder 0/34 (0%) 0 1/35 (2.9%) 1
    disconjugate gaze 1/34 (2.9%) 1 0/35 (0%) 0
    drainage 1/34 (2.9%) 1 0/35 (0%) 0
    left eye conjunctival hemorrhage 0/34 (0%) 0 1/35 (2.9%) 1
    right eye conjunctival hemorrhage 0/34 (0%) 0 1/35 (2.9%) 1
    swollen left eye 0/34 (0%) 0 1/35 (2.9%) 1
    Gastrointestinal disorders
    Abdominal distension 6/34 (17.6%) 6 1/35 (2.9%) 2
    Abdominal pain 12/34 (35.3%) 18 4/35 (11.4%) 4
    Bloating 3/34 (8.8%) 3 2/35 (5.7%) 4
    Colonic hemorrhage 1/34 (2.9%) 1 0/35 (0%) 0
    Constipation 17/34 (50%) 35 11/35 (31.4%) 14
    Dark Stool 0/34 (0%) 0 1/35 (2.9%) 1
    Diarrhea 18/34 (52.9%) 31 15/35 (42.9%) 22
    Dry mouth 6/34 (17.6%) 8 6/35 (17.1%) 7
    Dyspepsia 3/34 (8.8%) 4 2/35 (5.7%) 2
    Dysphagia 2/34 (5.9%) 2 1/35 (2.9%) 2
    Esophageal hemorrhage 1/34 (2.9%) 1 0/35 (0%) 0
    Esophageal pain 1/34 (2.9%) 1 0/35 (0%) 0
    Esophageal ulcer 1/34 (2.9%) 1 0/35 (0%) 0
    Flatulence 5/34 (14.7%) 7 1/35 (2.9%) 1
    Gastric ulcer 1/34 (2.9%) 1 1/35 (2.9%) 1
    Gastritis 1/34 (2.9%) 1 0/35 (0%) 0
    Gastroesophageal reflux disease 4/34 (11.8%) 4 0/35 (0%) 0
    Gastrointestinal pain 1/34 (2.9%) 1 0/35 (0%) 0
    Gum Abscess 0/34 (0%) 0 1/35 (2.9%) 1
    Hemorrhoids 0/34 (0%) 0 1/35 (2.9%) 1
    Mucositis oral 15/34 (44.1%) 30 24/35 (68.6%) 46
    Nausea 22/34 (64.7%) 51 13/35 (37.1%) 18
    Oral pain 2/34 (5.9%) 2 8/35 (22.9%) 9
    Rectal fistula 0/34 (0%) 0 1/35 (2.9%) 2
    Rectal hemorrhage 3/34 (8.8%) 3 0/35 (0%) 0
    Rectal mucositis 2/34 (5.9%) 2 1/35 (2.9%) 1
    Rectal pain 1/34 (2.9%) 1 0/35 (0%) 0
    Stomach pain 2/34 (5.9%) 3 1/35 (2.9%) 1
    Toothache 1/34 (2.9%) 1 0/35 (0%) 0
    Upper gastrointestinal hemorrhage 1/34 (2.9%) 1 0/35 (0%) 0
    Vomiting 18/34 (52.9%) 40 12/35 (34.3%) 15
    mucoid diarrhea 1/34 (2.9%) 1 0/35 (0%) 0
    General disorders
    Chills 9/34 (26.5%) 12 8/35 (22.9%) 16
    Edema face 6/34 (17.6%) 12 11/35 (31.4%) 12
    Edema limbs 17/34 (50%) 52 14/35 (40%) 24
    Edema trunk 1/34 (2.9%) 2 0/35 (0%) 0
    Fatigue 28/34 (82.4%) 93 18/35 (51.4%) 35
    Fever 8/34 (23.5%) 15 8/35 (22.9%) 11
    Flu like symptoms 2/34 (5.9%) 4 2/35 (5.7%) 3
    Gait disturbance 3/34 (8.8%) 5 1/35 (2.9%) 2
    Infusion related reaction 1/34 (2.9%) 1 1/35 (2.9%) 1
    Injection site reaction 1/34 (2.9%) 1 2/35 (5.7%) 2
    Localized edema 1/34 (2.9%) 1 1/35 (2.9%) 2
    Malaise 1/34 (2.9%) 1 0/35 (0%) 0
    Night Sweats 1/34 (2.9%) 1 0/35 (0%) 0
    Non-cardiac chest pain 7/34 (20.6%) 8 0/35 (0%) 0
    Pain 5/34 (14.7%) 15 2/35 (5.7%) 5
    dry nose 1/34 (2.9%) 1 0/35 (0%) 0
    night sweats 0/34 (0%) 0 1/35 (2.9%) 1
    Hepatobiliary disorders
    stent replaced - obstructed by tumor 1/34 (2.9%) 1 0/35 (0%) 0
    Immune system disorders
    Allergic reaction 0/34 (0%) 0 1/35 (2.9%) 4
    Infections and infestations
    Catheter related infection 0/34 (0%) 0 1/35 (2.9%) 1
    Eye infection 0/34 (0%) 0 2/35 (5.7%) 3
    Mucosal infection 1/34 (2.9%) 1 1/35 (2.9%) 1
    Papulopustular rash 2/34 (5.9%) 2 0/35 (0%) 0
    Paronychia 2/34 (5.9%) 10 1/35 (2.9%) 1
    Penile infection 1/34 (2.9%) 1 0/35 (0%) 0
    Pharyngitis 1/34 (2.9%) 1 1/35 (2.9%) 2
    R big toe infection 1/34 (2.9%) 2 0/35 (0%) 0
    Sinusitis 0/34 (0%) 0 1/35 (2.9%) 1
    Skin infection 4/34 (11.8%) 9 5/35 (14.3%) 8
    Thrush 0/34 (0%) 0 2/35 (5.7%) 2
    Tooth infection 1/34 (2.9%) 1 0/35 (0%) 0
    Urinary tract infection 2/34 (5.9%) 2 1/35 (2.9%) 1
    Vaginal infection 0/34 (0%) 0 1/35 (2.9%) 1
    infected necrotic tumor 0/34 (0%) 0 1/35 (2.9%) 1
    Injury, poisoning and procedural complications
    Bruising 1/34 (2.9%) 1 1/35 (2.9%) 1
    Fall 0/34 (0%) 0 2/35 (5.7%) 3
    Fracture 1/34 (2.9%) 6 0/35 (0%) 0
    Investigations
    Activated partial thromboplastin time pr 2/34 (5.9%) 2 2/35 (5.7%) 4
    Alanine aminotransferase increased 11/34 (32.4%) 24 10/35 (28.6%) 13
    Alkaline phosphatase increased 9/34 (26.5%) 27 14/35 (40%) 29
    Aspartate aminotransferase increased 19/34 (55.9%) 53 18/35 (51.4%) 28
    Blood bilirubin increased 3/34 (8.8%) 4 1/35 (2.9%) 1
    CD4 lymphocytes decreased 1/34 (2.9%) 1 3/35 (8.6%) 5
    CPK increased 1/34 (2.9%) 1 0/35 (0%) 0
    Cholesterol high 10/34 (29.4%) 48 13/35 (37.1%) 29
    Creatinine increased 4/34 (11.8%) 5 4/35 (11.4%) 11
    INR increased 2/34 (5.9%) 7 5/35 (14.3%) 7
    Lipase increased 0/34 (0%) 0 1/35 (2.9%) 1
    Lymphocyte count decreased 6/34 (17.6%) 12 14/35 (40%) 38
    Lymphocyte count increased 0/34 (0%) 0 1/35 (2.9%) 2
    Neutrophil count decreased 11/34 (32.4%) 25 14/35 (40%) 44
    Platelet count decreased 15/34 (44.1%) 42 24/35 (68.6%) 49
    QTc prolonged 0/34 (0%) 0 1/35 (2.9%) 1
    Weight gain 2/34 (5.9%) 7 0/35 (0%) 0
    Weight loss 5/34 (14.7%) 11 3/35 (8.6%) 7
    White blood cell decreased 12/34 (35.3%) 42 14/35 (40%) 43
    alanine aminotransferase decreased 1/34 (2.9%) 1 0/35 (0%) 0
    eosinophilia 0/34 (0%) 0 1/35 (2.9%) 1
    ionized calcium 0/34 (0%) 0 1/35 (2.9%) 1
    Metabolism and nutrition disorders
    Acidosis 1/34 (2.9%) 1 0/35 (0%) 0
    Anorexia 14/34 (41.2%) 34 15/35 (42.9%) 21
    Chloride increased 1/34 (2.9%) 1 0/35 (0%) 0
    Dehydration 2/34 (5.9%) 2 3/35 (8.6%) 3
    Hypercalcemia 1/34 (2.9%) 1 0/35 (0%) 0
    Hyperglycemia 6/34 (17.6%) 16 13/35 (37.1%) 27
    Hyperkalemia 1/34 (2.9%) 4 1/35 (2.9%) 1
    Hypermagnesemia 2/34 (5.9%) 2 2/35 (5.7%) 2
    Hypernatremia 1/34 (2.9%) 1 0/35 (0%) 0
    Hypertriglyceridemia 11/34 (32.4%) 36 13/35 (37.1%) 26
    Hypoalbuminemia 20/34 (58.8%) 37 18/35 (51.4%) 37
    Hypocalcemia 7/34 (20.6%) 14 11/35 (31.4%) 16
    Hypoglycemia 3/34 (8.8%) 3 3/35 (8.6%) 3
    Hypokalemia 8/34 (23.5%) 14 13/35 (37.1%) 28
    Hypomagnesemia 4/34 (11.8%) 8 1/35 (2.9%) 1
    Hyponatremia 11/34 (32.4%) 34 9/35 (25.7%) 13
    Hypophosphatemia 7/34 (20.6%) 11 3/35 (8.6%) 7
    Increased LDH 1/34 (2.9%) 1 0/35 (0%) 0
    Iron deficiency 0/34 (0%) 0 1/35 (2.9%) 1
    LDH increased 0/34 (0%) 0 1/35 (2.9%) 1
    Obesity 7/34 (20.6%) 50 2/35 (5.7%) 4
    increased LDH 0/34 (0%) 0 1/35 (2.9%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia 4/34 (11.8%) 7 2/35 (5.7%) 2
    Arthritis 1/34 (2.9%) 1 1/35 (2.9%) 1
    Back pain 8/34 (23.5%) 14 6/35 (17.1%) 8
    Bone pain 1/34 (2.9%) 2 1/35 (2.9%) 2
    Chest wall pain 4/34 (11.8%) 16 2/35 (5.7%) 2
    Flank pain 4/34 (11.8%) 6 0/35 (0%) 0
    Generalized body aches 1/34 (2.9%) 1 0/35 (0%) 0
    Generalized muscle weakness 4/34 (11.8%) 6 4/35 (11.4%) 4
    Muscle weakness lower limb 2/34 (5.9%) 5 0/35 (0%) 0
    Muscle weakness upper limb 1/34 (2.9%) 1 1/35 (2.9%) 1
    Myalgia 4/34 (11.8%) 11 2/35 (5.7%) 3
    Neck pain 3/34 (8.8%) 5 2/35 (5.7%) 3
    Pain in extremity 12/34 (35.3%) 34 9/35 (25.7%) 13
    Pelvic soft tissue necrosis 1/34 (2.9%) 1 0/35 (0%) 0
    Weakness 1/34 (2.9%) 1 0/35 (0%) 0
    muscle cramps 0/34 (0%) 0 1/35 (2.9%) 1
    muscle spasm, left hip 1/34 (2.9%) 1 0/35 (0%) 0
    shoulder pain (L) w/ cough 1/34 (2.9%) 1 0/35 (0%) 0
    twitching 1/34 (2.9%) 1 0/35 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumor pain 9/34 (26.5%) 36 2/35 (5.7%) 5
    Nervous system disorders
    Ataxia 1/34 (2.9%) 1 1/35 (2.9%) 1
    Concentration impairment 1/34 (2.9%) 1 0/35 (0%) 0
    Depressed level of consciousness 1/34 (2.9%) 1 1/35 (2.9%) 1
    Dizziness 4/34 (11.8%) 16 4/35 (11.4%) 8
    Dysarthria 0/34 (0%) 0 1/35 (2.9%) 1
    Dysgeusia 6/34 (17.6%) 17 6/35 (17.1%) 9
    Facial muscle weakness 1/34 (2.9%) 1 1/35 (2.9%) 1
    Headache 7/34 (20.6%) 9 4/35 (11.4%) 4
    L facial palsy 1/34 (2.9%) 1 0/35 (0%) 0
    Lethargy 6/34 (17.6%) 6 1/35 (2.9%) 1
    Memory impairment 3/34 (8.8%) 3 1/35 (2.9%) 1
    Myelitis 0/34 (0%) 0 1/35 (2.9%) 2
    Neuralgia 0/34 (0%) 0 1/35 (2.9%) 1
    Paresthesia 4/34 (11.8%) 6 2/35 (5.7%) 2
    Peripheral motor neuropathy 1/34 (2.9%) 1 1/35 (2.9%) 3
    Peripheral sensory neuropathy 1/34 (2.9%) 1 2/35 (5.7%) 3
    Phantom pain 1/34 (2.9%) 1 0/35 (0%) 0
    Presyncope 1/34 (2.9%) 1 1/35 (2.9%) 1
    Radiculitis 1/34 (2.9%) 1 0/35 (0%) 0
    Somnolence 3/34 (8.8%) 5 3/35 (8.6%) 3
    Spasticity 1/34 (2.9%) 1 1/35 (2.9%) 1
    Syncope 1/34 (2.9%) 1 0/35 (0%) 0
    Tremor 2/34 (5.9%) 3 1/35 (2.9%) 1
    Psychiatric disorders
    Anxiety 5/34 (14.7%) 8 5/35 (14.3%) 5
    Confusion 1/34 (2.9%) 1 2/35 (5.7%) 2
    Depression 6/34 (17.6%) 12 4/35 (11.4%) 7
    Insomnia 11/34 (32.4%) 21 6/35 (17.1%) 8
    Libido decreased 3/34 (8.8%) 11 2/35 (5.7%) 3
    Lucid per physical exam 0/34 (0%) 0 1/35 (2.9%) 1
    Restlessness 0/34 (0%) 0 2/35 (5.7%) 3
    Suicidal ideation 1/34 (2.9%) 1 0/35 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 2/34 (5.9%) 2 1/35 (2.9%) 1
    Dysuria 1/34 (2.9%) 1 0/35 (0%) 0
    Hematuria 1/34 (2.9%) 1 3/35 (8.6%) 3
    Nocturia 1/34 (2.9%) 1 0/35 (0%) 0
    Proteinuria 5/34 (14.7%) 5 2/35 (5.7%) 2
    Renal calculi 0/34 (0%) 0 1/35 (2.9%) 1
    Urinary frequency 1/34 (2.9%) 1 0/35 (0%) 0
    Urinary incontinence 1/34 (2.9%) 1 0/35 (0%) 0
    Urinary tract obstruction 0/34 (0%) 0 1/35 (2.9%) 1
    Urinary tract pain 0/34 (0%) 0 1/35 (2.9%) 1
    Urine discoloration 3/34 (8.8%) 3 1/35 (2.9%) 1
    Reproductive system and breast disorders
    Erectile dysfunction 1/34 (2.9%) 8 1/35 (2.9%) 1
    Genital edema 2/34 (5.9%) 9 0/35 (0%) 0
    Irregular menstruation 1/34 (2.9%) 1 0/35 (0%) 0
    Pelvic pain 3/34 (8.8%) 11 1/35 (2.9%) 1
    Penile pain 1/34 (2.9%) 2 0/35 (0%) 0
    Testicular pain 1/34 (2.9%) 1 0/35 (0%) 0
    Vaginal dryness 0/34 (0%) 0 1/35 (2.9%) 1
    Vaginal mucositis 1/34 (2.9%) 1 0/35 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Atelectasis 1/34 (2.9%) 1 0/35 (0%) 0
    Bronchopulmonary hemorrhage 1/34 (2.9%) 3 0/35 (0%) 0
    Bronchospasm 0/34 (0%) 0 1/35 (2.9%) 1
    Chest Congestion 1/34 (2.9%) 1 0/35 (0%) 0
    Cough 14/34 (41.2%) 41 7/35 (20%) 9
    Dyspnea 15/34 (44.1%) 39 9/35 (25.7%) 16
    Epistaxis 5/34 (14.7%) 8 7/35 (20%) 7
    Hiccups 0/34 (0%) 0 1/35 (2.9%) 1
    Hypoxia 2/34 (5.9%) 2 2/35 (5.7%) 2
    Laryngeal inflammation 1/34 (2.9%) 1 0/35 (0%) 0
    Nasal congestion 2/34 (5.9%) 2 2/35 (5.7%) 2
    Pleural effusion 3/34 (8.8%) 15 3/35 (8.6%) 3
    Pleuritic pain 0/34 (0%) 0 1/35 (2.9%) 1
    Pneumonitis 0/34 (0%) 0 1/35 (2.9%) 1
    Pneumothorax 1/34 (2.9%) 1 0/35 (0%) 0
    Postnasal drip 0/34 (0%) 0 1/35 (2.9%) 2
    Productive cough 4/34 (11.8%) 7 2/35 (5.7%) 2
    Sleep apnea 1/34 (2.9%) 2 0/35 (0%) 0
    Sneezing 1/34 (2.9%) 1 1/35 (2.9%) 1
    Sore throat 4/34 (11.8%) 4 3/35 (8.6%) 4
    Voice alteration 1/34 (2.9%) 1 1/35 (2.9%) 1
    Wheezing 3/34 (8.8%) 3 0/35 (0%) 0
    Skin and subcutaneous tissue disorders
    Alopecia 4/34 (11.8%) 26 6/35 (17.1%) 11
    Dry skin 6/34 (17.6%) 23 6/35 (17.1%) 11
    Erythema multiforme 1/34 (2.9%) 1 2/35 (5.7%) 3
    Hyperhidrosis 1/34 (2.9%) 1 0/35 (0%) 0
    Nail discoloration 2/34 (5.9%) 2 1/35 (2.9%) 1
    Nail loss 1/34 (2.9%) 1 1/35 (2.9%) 1
    Nail ridging 0/34 (0%) 0 1/35 (2.9%) 1
    Pain of skin 3/34 (8.8%) 3 1/35 (2.9%) 1
    Palmar-plantar erythrodysesthesia syndro 0/34 (0%) 0 1/35 (2.9%) 1
    Periorbital edema 1/34 (2.9%) 1 4/35 (11.4%) 4
    Pruritus 4/34 (11.8%) 5 9/35 (25.7%) 19
    Rash acneiform 22/34 (64.7%) 67 17/35 (48.6%) 40
    Rash maculo-papular 6/34 (17.6%) 8 8/35 (22.9%) 12
    Skin hyperpigmentation 2/34 (5.9%) 2 1/35 (2.9%) 1
    Skin ulceration 2/34 (5.9%) 10 1/35 (2.9%) 1
    Telangiectasia 1/34 (2.9%) 2 0/35 (0%) 0
    Urticaria 0/34 (0%) 0 1/35 (2.9%) 1
    burning in armpits 1/34 (2.9%) 1 0/35 (0%) 0
    cellulitis 0/34 (0%) 0 1/35 (2.9%) 2
    cut on palm 1/34 (2.9%) 1 0/35 (0%) 0
    folliculitis 1/34 (2.9%) 1 0/35 (0%) 0
    ingrown toe nail 0/34 (0%) 0 1/35 (2.9%) 1
    pin point rash/non red/dry skin 0/34 (0%) 0 1/35 (2.9%) 1
    pin point rash/non-red/dry skin 0/34 (0%) 0 1/35 (2.9%) 1
    redness and liquid in stump area 1/34 (2.9%) 1 0/35 (0%) 0
    small fissures on finger pads 1/34 (2.9%) 1 0/35 (0%) 0
    Vascular disorders
    Flushing 0/34 (0%) 0 1/35 (2.9%) 2
    Hot flashes 2/34 (5.9%) 3 0/35 (0%) 0
    Hypertension 19/34 (55.9%) 81 12/35 (34.3%) 33
    Hypotension 3/34 (8.8%) 3 1/35 (2.9%) 1
    Lymphedema 1/34 (2.9%) 10 4/35 (11.4%) 6
    Thromboembolic event 2/34 (5.9%) 6 3/35 (8.6%) 3
    venous stasis changes, legs 1/34 (2.9%) 1 0/35 (0%) 0

    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.

    Results Point of Contact

    Name/Title DCC Project Administrator
    Organization California Cancer Consortium
    Phone 626-256-4673 ext 60094
    Email CCCP@coh.org
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01206140
    Other Study ID Numbers:
    • NCI-2011-02532
    • NCI-2011-02532
    • CDR0000685408
    • CHNMC-PHII-95
    • NCCN-T06
    • PHII-95
    • 8412
    • N01CM00038
    • P30CA033572
    First Posted:
    Sep 21, 2010
    Last Update Posted:
    Oct 5, 2015
    Last Verified:
    Jan 1, 2015