Phase I/IIa Trial of Gemcitabine Plus Trastuzumab and Pertuzumab in Previously Treated Metastatic HER2+ Breast Cancer
The purpose of this study is to evaluate the safety and activity of gemcitabine plus trastuzumab and pertuzumab in patients with metastatic human epidermal growth factor receptor 2 (HER2)+ breast cancer who have progressed on at least one prior line of chemotherapy plus HER2 targeted agent such as T-DM1, trastuzumab, or lapatinib.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/IIa Trial of Gemcitabine Plus Trastuzumab and Pertuzumab in Previously Treated Metastatic HER2+ Breast Cancer|
- Phase I: Recommended Phase II Dose [ Time Frame: Upon Determination of Phase II Dose - Approximately 6 Months ] [ Designated as safety issue: Yes ]Establishing the recommended phase II dose for the combination of gemcitabine+trastuzumab+pertuzumab with safety data described using Common Terminology Criteria for Adverse Events (CTCAE) 4.0 terminology. Any patient who receives any dose of the study treatment will be evaluated for the safety/toxicity endpoints in the trial.
- Phase II: Objective Response Rate (ORR) [ Time Frame: Up to 36 Months ] [ Designated as safety issue: No ]Objective Response Rate: Complete Response (CR) + Partial Response (PR) using Response Evaluation in Solid Tumors (RECIST) 1.1 criteria for the combination of gemcitabine+trastuzumab+pertuzumab at the recommended phase II dose. Any patient who receives any dose of the study treatment will be evaluated for the safety/toxicity endpoints in the trial. To be considered evaluable for the primary efficacy endpoint (ORR) the patient must undergo two treatment cycles followed by a response scan. CR: Disappearance of all evidence of tumor for at least two cycles of therapy. Tumor markers must be normal. PR: At least a 30% decrease in the sum of the longest diameter of target lesions, taking a reference the baseline sum longest diameter.
- Phase II: Progression Free Survival (PFS) [ Time Frame: Up to 36 Months ] [ Designated as safety issue: No ]Median progression free survival (in months) for all patients evaluable for response. The time-to-event data will be summarized using Kaplan-Meir curve method for all patients who are evaluable for the ORR endpoint. Progressive disease (PD): At least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the beginning of treatment or the appearance of one or more new lesions.
|Study Start Date:||September 2014|
|Estimated Study Completion Date:||March 2016|
|Estimated Primary Completion Date:||March 2016 (Final data collection date for primary outcome measure)|
Experimental: Phase I Dose Escalation / Phase II Treatment
Single arm, non-randomized, open label phase I/II multisite Simon two stage minimax trial. Gemcitabine plus trastuzumab and pertuzumab.
The phase I trial will start at the recommended phase II dose (RP2D) for gemcitabine but will have a de-escalation dose levels in the event that an unacceptable toxicity requires dose reduction. Dose level 0 = gemcitabine (1200mg/m2) IV D1,8 q21 days; Dose level -1 = gemcitabine (1000mg/m2) IV D1,8 q21 days; Dose level -2 = gemcitabine (850mg/m2) IV D1,8 q21 days. The RP2D will be the dose level where 0-1 dose limiting toxicities (DLTs) in six patients occur.
Other Name: GEMZAR®Drug: Trastuzumab
Trastuzumab will be given using an 8mg/kg loading dose on cycle one, day one (C1D1), followed by 6mg/kg IV on subsequent cycles every (q) 21 days.
Other Name: Herceptin®Drug: Pertuzumab
Pertuzumab will be given using an 840mg IV loading dose on C1D1, followed by 420mg IV on subsequent cycles q21 days.
Other Name: PERJETA®
Please refer to this study by its ClinicalTrials.gov identifier: NCT02139358
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute||Recruiting|
|Tampa, Florida, United States, 33612|
|Contact: Kayla Cox 813-745-5975 email@example.com|
|Principal Investigator: Hatem Soliman, M.D.|
|Sub-Investigator: Hyo Han, M.D.|
|Sub-Investigator: Roohi Ismail-Khan, M.D.|
|Sub-Investigator: Loretta Loftus, M.D.|
|Sub-Investigator: Susan Minton, D.O.|
|Sub-Investigator: Paul Chervenick, M.D.|
|Principal Investigator:||Hatem Soliman, M.D.||H. Lee Moffitt Cancer Center and Research Institute|