Phase I/IIa Trial of Gemcitabine Plus Trastuzumab and Pertuzumab in Previously Treated Metastatic HER2+ Breast Cancer
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|ClinicalTrials.gov Identifier: NCT02139358|
Recruitment Status : Active, not recruiting
First Posted : May 15, 2014
Results First Posted : July 20, 2018
Last Update Posted : April 3, 2019
|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|
|Actual Primary Completion Date :||April 24, 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 (1200 mg/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 q 21 days.
Other Name: PERJETA®
- Phase I: Recommended Phase II Dose (RP2D) [ Time Frame: 6 Months ]The RP2D dose in mg/m^2 of gemcitabine along with standard doses of pertuzumab (840 mg loading/420 mg maintenance) and Herceptin (8 mg/kg loading, 6 mg/kg maintenance). Safety data to be described using Common Terminology Criteria for Adverse Events (CTCAE) 4.0 terminology. Any participant 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: Response according to Response Evaluation in Solid Tumors (RECIST) 1.1 for the combination of gemcitabine+trastuzumab+pertuzumab at the recommended phase II dose. Complete Response (CR): Disappearance of all evidence of tumor for at least two cycles of therapy. Tumor markers must be normal. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter of target lesions, taking a reference the baseline sum longest diameter. Stable Disease (SD): Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started. 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.
- Phase II: Progression Free Survival (PFS) [ Time Frame: Up to 12 months ]Median progression free survival (in months) for all participants 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.
- Overall Survival (OS) [ Time Frame: Up to 36 months ]Median overall survival (in months) for all participants evaluable for response. The length of time from the start of treatment that participants are still alive.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
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|