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Trial record 37 of 50 for:    MK-2206

MK-2206, Paclitaxel and Trastuzumab in Treating Patients With HER2-overexpressing Solid Tumor Malignancies

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ClinicalTrials.gov Identifier: NCT01235897
Recruitment Status : Completed
First Posted : November 8, 2010
Results First Posted : November 19, 2013
Last Update Posted : April 17, 2014
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of California, San Francisco

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Advanced Solid Tumors
Tumors
Cancer
Interventions Drug: MK-2206
Drug: Paclitaxel
Drug: Trastuzumab
Enrollment 17
Recruitment Details Patients were enrolled on the study between April 2011 and January 2013. This is a phase one study; the number enrolled was guided by ongoing toxicity assessment.
Pre-assignment Details 17 patients were initially enrolled; however, one participant experienced rapid progression of disease before receiving any study treatment.
Arm/Group Title MK-2206
Hide Arm/Group Description MK-2206 : MK-2206 given orally at a dose of 135 mg weekly Trastuzumab : 2 mg/kg weekly after a 1-time loading dose of 4 mg/kg - trastuzumab Paclitaxel : 80 mg/m2 weekly - paclitaxel
Period Title: Overall Study
Started 16
Completed 16
Not Completed 0
Arm/Group Title MK-2206
Hide Arm/Group Description MK-2206 : MK-2206 given orally at a dose of 135 mg weekly Trastuzumab : 2 mg/kg weekly after a 1-time loading dose of 4 mg/kg - trastuzumab Paclitaxel : 80 mg/m2 weekly - paclitaxel
Overall Number of Baseline Participants 16
Hide Baseline Analysis Population Description
all subjects receiving study treatment were included in study analysis
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 16 participants
52
(31 to 78)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants
Female
14
  87.5%
Male
2
  12.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 16 participants
16
1.Primary Outcome
Title Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose of MK-2206 Administered Weekly in Combination With Weekly Paclitaxel 80 mg/m^2 and Trastuzumab 2 mg/m^2
Hide Description The MTD was defined as the dose level resulting in 3 or fewer DLTs in 11 patients, per the modified toxicity probability interval (TPI) method (Ji Y, Li Y, Nebiyou Bekele B: Dose-finding in phase I clinical trials based on toxicity probability intervals. Clin Trials 4:235-244, 2007), and confirmed in 4 additional patients. Based on interim toxicity data from other studies, the dose was not escalated beyond 135 mg weekly.
Time Frame 30 days from initiation of dose
Hide Outcome Measure Data
Hide Analysis Population Description
Sixteen participants completed at least one cycle of therapy and were evaluable for DLT per protocol. Patients were assessed for DLT during the first 4-week cycle.
Arm/Group Title MK-2206
Hide Arm/Group Description:
MK-2206 : MK-2206 given orally at a dose of 135 mg weekly Trastuzumab : 2 mg/kg weekly after a 1-time loading dose of 4 mg/kg - trastuzumab Paclitaxel : 80 mg/m2 weekly - paclitaxel
Overall Number of Participants Analyzed 16
Measure Type: Number
Unit of Measure: mg
135
2.Secondary Outcome
Title Best Disease Response by Response Evaluation Criteria in Solid Tumor (RECIST), Version 1.1
Hide Description

Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.

Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study

Non-PR/Non-PD: clinical response of chest wall disease not evaluable by RECIST

Time Frame 60 days after dose inititation
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis included all patients receiving at least 8 weeks of study therapy
Arm/Group Title MK-2206
Hide Arm/Group Description:
MK-2206 given orally at a dose of 135 mg weekly + Trastuzumab 2 mg/kg weekly after a 1-time loading dose of 4 mg/kg + Paclitaxel 80 mg/m2 weekly
Overall Number of Participants Analyzed 16
Measure Type: Number
Unit of Measure: participants
Complete Response (CR) 3
Partial Response (PR) 7
Progressive Disease (PD) 1
Stable Disease (SD) 4
Non-CR/Non-PD 1
Time Frame 40 weeks
Adverse Event Reporting Description Toxicity assessment continued as long as patient received study treatment; the longest on-study duration was 40 weeks
 
Arm/Group Title MK-2206
Hide Arm/Group Description MK-2206 : MK-2206 given orally at a dose of 135 mg weekly Trastuzumab : 2 mg/kg weekly after a 1-time loading dose of 4 mg/kg - trastuzumab Paclitaxel : 80 mg/m2 weekly - paclitaxel
All-Cause Mortality
MK-2206
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
MK-2206
Affected / at Risk (%) # Events
Total   5/17 (29.41%)    
General disorders   
Hemorrhage  1  1/17 (5.88%)  1
Death  1 [1]  3/17 (17.65%)  3
Pain - Abdominal  1  1/17 (5.88%)  2
Infection with rash grade 3 ANC  1  1/17 (5.88%)  1
Hepatobiliary disorders   
Liver dysfunction  1  1/17 (5.88%)  1
Nervous system disorders   
Pain - neuralgia  1  1/17 (5.88%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (Unspecified)
[1]
Death during follow-up (disease progression)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
MK-2206
Affected / at Risk (%) # Events
Total   17/17 (100.00%)    
Blood and lymphatic system disorders   
Anemia  1 [1]  9/17 (52.94%)  14
Neutropenia  1  14/17 (82.35%)  30
Hyperglycemia  1  17/17 (100.00%)  31
Dehydration  1  2/17 (11.76%)  2
Hypoalbumenia  1  2/17 (11.76%)  3
Hypercalcemia  1  1/17 (5.88%)  1
Epistaxis  1  5/17 (29.41%)  8
Decreased Hematocrit  1  16/17 (94.12%)  19
Decreased lymphocytes  1  2/17 (11.76%)  2
Decreased monocytes  1  2/17 (11.76%)  3
Decreased RBC  1  1/17 (5.88%)  1
Decreased WBC  1  7/17 (41.18%)  16
Decreased Hemoglobin  1  8/17 (47.06%)  15
Decreased platelets  1  4/17 (23.53%)  7
Decreased Potassium  1  1/17 (5.88%)  1
Decreased Magnesium  1  1/17 (5.88%)  1
Decreased Calcium  1  1/17 (5.88%)  2
Elevated BUN  1  1/17 (5.88%)  1
Eye disorders   
Eye swelling  1  1/17 (5.88%)  1
Gastrointestinal disorders   
Diarrhea  1  11/17 (64.71%)  18
Constipation  1  1/17 (5.88%)  1
Intermittent GERD pain  1  1/17 (5.88%)  1
Dyspepsia  1  3/17 (17.65%)  3
Hemorrhoid  1  1/17 (5.88%)  1
Stomatitis  1  6/17 (35.29%)  8
Vomiting  1  2/17 (11.76%)  3
Abdominal pain  1  1/17 (5.88%)  1
General disorders   
Fatigue  1  11/17 (64.71%)  19
Anorexia/weight loss  1  12/17 (70.59%)  15
Nausea  1  6/17 (35.29%)  6
Altered Taste  1  3/17 (17.65%)  3
Insomnia  1  4/17 (23.53%)  4
Headache  1  2/17 (11.76%)  2
Groin pain  1  1/17 (5.88%)  1
Cough  1  1/17 (5.88%)  1
Hepatobiliary disorders   
Elevated ALT  1  7/17 (41.18%)  7
Elevated AST  1  9/17 (52.94%)  16
Hyperbilirubin  1  4/17 (23.53%)  8
Hypobilirubin  1  1/17 (5.88%)  1
Infections and infestations   
Infection  1  2/17 (11.76%)  3
Musculoskeletal and connective tissue disorders   
Xerostomia  1  1/17 (5.88%)  1
Lower extremity weakness  1  1/17 (5.88%)  1
Peripheral Neuropathy  1  10/17 (58.82%)  19
Arthralgia  1  3/17 (17.65%)  4
Myalgia  1  2/17 (11.76%)  2
Left Calf Pain  1  1/17 (5.88%)  1
Psychiatric disorders   
Depression  1  1/17 (5.88%)  1
Anxiety  1  2/17 (11.76%)  2
Renal and urinary disorders   
Elevated Creatinine  1  1/17 (5.88%)  2
Hemoglobinuria  1  1/17 (5.88%)  1
Proteinuria  1  1/17 (5.88%)  1
Cystitis  1  1/17 (5.88%)  1
Urinary retention  1  1/17 (5.88%)  1
Respiratory, thoracic and mediastinal disorders   
Rhinorrhea  1  4/17 (23.53%)  4
Sinus Pain  1  1/17 (5.88%)  1
Dyspnea  1  1/17 (5.88%)  1
Skin and subcutaneous tissue disorders   
Rash  1  15/17 (88.24%)  24
Cracks to fingertips  1  1/17 (5.88%)  1
Alopecia  1  10/17 (58.82%)  11
Nail changes  1  3/17 (17.65%)  6
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (Unspecified)
[1]
For all AEs, # participants affected reported here as # events. Patients may have experienced an event more than one time and were clinically managed for recurring toxicity; however, study data are not structured for analysis by patient.
MTD was defined as a dose resulting in 3 or fewer DLTs in 11 patients, plus a cohort of 4 patients by a modified TPI dose escalation method. Based on interim toxicity data from other studies, study dose did not exceed 135mg weekly.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Jo Chien, MD
Organization: University of California, San Francisco
Phone: 415-885-7577
EMail: crss@ucsf.edu
Layout table for additonal information
Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01235897     History of Changes
Other Study ID Numbers: 10998
First Submitted: November 4, 2010
First Posted: November 8, 2010
Results First Submitted: July 29, 2013
Results First Posted: November 19, 2013
Last Update Posted: April 17, 2014