Temsirolimus Plus Neratinib for Patients With Metastatic HER2-Amplified or Triple Negative Breast Cancer
|ClinicalTrials.gov Identifier: NCT01111825|
Recruitment Status : Completed
First Posted : April 28, 2010
Results First Posted : November 7, 2017
Last Update Posted : November 7, 2017
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Drug: Temsirolimus Drug: Neratinib||Phase 1 Phase 2|
Phase I Design A standard, 3+3, dose escalation schedule to determine the MTD of temsirolimus in combination with neratinib with no intrapatient dose escalation and a starting dose of temsirolimus 8 mg administered intravenously (IV) weekly (dose level 1) and three patients enrolled in each cohort.
Phase II Design The phase II portion of this trial is comprised of three cohorts. Two of the cohorts utilized a Simon two-stage design to determine the sample size to assess the efficacy of temsirolimus when administered in combination with neratinib: HER2-amplified and triple negative breast cancer. The third cohort was a single stage design with HER2-amplified patients and dose escalation.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||99 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Trial of Temsirolimus Plus Neratinib for Patients With Metastatic HER2-Amplified or Triple Negative Breast Cancer|
|Actual Study Start Date :||April 2010|
|Primary Completion Date :||July 2016|
|Study Completion Date :||July 2016|
Experimental: Temsirolimus plus Neratinib
This is an open-label, single arm, dose-escalation phase I-II study to determine the maximum tolerated dose (MTD) of temsirolimus with daily neratinib, and to determine the safety and efficacy of this combination when given to patients with advanced breast carcinoma. Patients with trastuzumab-refractory HER2-amplified disease or triple negative disease will be enrolled in both phases of this clinical trial.
28 day treatment cycle Phase 1
Other Name: ToriselDrug: Neratinib
28 day treatment cycle
• 240 mg orally daily
Other Name: Nerlynx
- Objective Response Rate (ORR) (Phase II) [ Time Frame: From enrollment date to first documented response, or last tumor assessment, assessed up to two years ]
ORR is defined as proportion of subjects who achieved confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
A complete or partial response must be confirmed no less than 4-weeks after the criteria for response are initially met.
- Clinical Benefit Rate (CBR) [ Time Frame: From enrollment date to first documented response, or last tumor assessment, assessed up to two years ]
Defined as the proportion of patients who achieved objective response (CR or PR) or SD for at least 24 weeks per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; 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.
Clinical Benefit (CB) = CR + PR + SD >= 24 weeks.
- Duration of Response (DOR) [ Time Frame: From first response to first PD or death, assessed up to two years. ]Measured from the time at which measurement criteria were first met for CR or PR (whichever status was recorded first), until the date of first recurrence, Progressive Disease (PD), or death was objectively documented, taking as a reference for PD the smallest measurements recorded since enrollment, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR; Progressive Disease (PD), At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, and/or the appearance of one or more new lesions.
- Progression-free Survival (PFS) [ Time Frame: From date of enrollment until the date of first documented progression, or date of death from any cause, whichever came first, assessed up to two years. ]Defined as time from date of enrollment until the first disease recurrence or progression or death due to any cause; censored at the last assessable evaluation or at the initiation of new anti-cancer therapy. Disease assessment is based on investigator tumor assessments. If no post-baseline tumor assessment then censored at enrollment date.
- Overall Survival (OS) [ Time Frame: From enrollment to date of death from any cause, or end of long term follow-up, assessed up to three years. ]Defined as the time from enrollment to death due to any cause; censored at the date last known alive.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01111825
|United States, Arizona|
|Western Regional Medical Center, Inc.|
|Goodyear, Arizona, United States, 85338|
|United States, California|
|USC/Norris Comprehensive Cancer Center|
|Los Angeles, California, United States, 90033|
|United States, New York|
|Memorial Sloan Kettering Cancer Center (MSKCC)|
|New York, New York, United States, 10065|
|Weill Cornell Medical College - New York - Presbyterian Hospital|
|New York, New York, United States, 10065|
|Roskilde, Denmark, 4000|
|Institut Gustave Roussy|
|Villejuif, France, 94800|
|UNIMED Medical Institute|
|Wan Chai, Hong Kong|
|Hospital Universitario Sant Joan de Reus|
|Tarragona, Reus, Spain, 43204|
|Hospital Universitario Vall d'Hebron|
|Barcelona, Spain, 08035|
|Hospital Universitari Arnau de Vilanova de Lleida|
|Lleida, Spain, 25006|
|Edinburgh Cancer Center, Western General Hospital|
|Edinburgh, United Kingdom, EH4 2XU|
|The Royal Marsden NHS Foundation Trust|
|London, United Kingdom, SW3 6JJ|
|Study Director:||Puma Biotechnology||Puma|