Phase I/IIa Trial of Gemcitabine Plus Trastuzumab and Pertuzumab in Previously Treated Metastatic HER2+ Breast Cancer
|ClinicalTrials.gov Identifier: NCT02139358|
Recruitment Status : Active, not recruiting
First Posted : May 15, 2014
Last Update Posted : May 1, 2018
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Drug: Gemcitabine Drug: Trastuzumab Drug: Pertuzumab||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/IIa Trial of Gemcitabine Plus Trastuzumab and Pertuzumab in Previously Treated Metastatic HER2+ Breast Cancer|
|Actual Study Start Date :||September 5, 2014|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||December 2019|
Experimental: 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 (1000 mg/m^2) IV D1,8 q21 days; Dose level -2 = gemcitabine (850 mg/m^2) 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®
Trastuzumab will be given using an 8 mg/kg loading dose on cycle one, day one (C1D1), followed by 6 mg/kg IV on subsequent cycles every (q) 21 days.
Other Name: Herceptin®
Pertuzumab will be given using an 840 mg IV loading dose on C1D1, followed by 420 mg IV on subsequent cycles q21 days.
Other Name: PERJETA®
- Phase I: Recommended Phase II Dose [ Time Frame: Upon Determination of Phase II Dose - Approximately 6 Months ]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 ]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 ]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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02139358
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Hatem Soliman, M.D.||H. Lee Moffitt Cancer Center and Research Institute|