Trial to Evaluate Efficacy and Safety of Pembrolizumab and Gemcitabine in HER2-negative ABC (PANGEA)
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|ClinicalTrials.gov Identifier: NCT03025880|
Recruitment Status : Active, not recruiting
First Posted : January 20, 2017
Last Update Posted : August 14, 2019
Study Design and Treatment:
This is a multicenter phase II trial, with an initial exploratory run-in-phase, to evaluate the efficacy and safety of pembrolizumab in combination with gemcitabine in patients with HER2-negative ABC that have previously received anthracyclines and taxanes (unless clinically contraindicated). In hormone receptor positive patients, previous treatment with 2 or more lines of hormone therapy will also be required. Patients must have at least one measurable lesion that can be accurately assessed at baseline and is suitable for repeated assessment by CT, MRI or plan X-ray. Approximately 53 patients (up to a maximum of 65 patients depending on the results of the run-in-phase) will be included in this trial.
|Condition or disease||Intervention/treatment||Phase|
|Advanced Breast Cancer||Drug: Pembrolizumab Drug: Gemcitabine||Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multicenter Phase II Trial to Evaluate the Efficacy and Safety of Pembrolizumab and Gemcitabine in Patients With HER2-negative Advanced Breast Cancer (ABC) "PANGEA-Breast"|
|Actual Study Start Date :||June 28, 2017|
|Actual Primary Completion Date :||June 3, 2019|
|Estimated Study Completion Date :||July 2020|
Experimental: Single arm
Eligible patients will be enrolled and treated with Pembrolizumab (P) at a dose of 200mg as an intravenous (IV) infusion on day 1 of each 21-day cycle in combination with Gemcitabine (G) at a dose of 1,250mg/m2 or 1,000mg/m2 (this dose will be explored in combination with P in the initial exploratory run-in-phase if necessary) as a IV infusion on day 1 and 8 of each 21-day cycle.
Treatment will be repeated on day 1 of each 21-day cycle until objective disease progression, clinical progression (under investigator criteria), unacceptable toxicity, death or withdrawal of consent, whichever occurs first. An initial exploratory run-in-phase will be performed to test the safety of the combination and determine the Recommended Phase II Dose (RP2D) of G in combination with fixed doses of P.
Pembrolizumab at a dose of 200mg as an intravenous (IV) 30 minutes infusion on day 1 of each 21-day cycle. Treatment will be repeated on day 1 of each 21-day cycle until objective disease progression, clinical progression (under investigator criteria), unacceptable toxicity, death or withdrawal of consent, whichever occurs first. Patients completing 24 months of uninterrupted treatment with pembrolizumab or 35 administrations of study medication will stop pembrolizumab treatment (though may continue with gemcitabine). Subjects who stop pembrolizumab after 24 months may be eligible for up to one year of additional pembrolizumab treatment if they progress after stopping it.
Other Name: Keytruda
Gemcitabine at a dose of 1,250mg/m2 as an intravenous (IV) 60 minutes infusion on day 1 and 8 of each 21-day cycle. Treatment will be repeated on day 1 of each 21-day cycle until objective disease progression, clinical progression (under investigator criteria), unacceptable toxicity, death or withdrawal of consent, whichever occurs first.
Other Name: Gemzar
- Incidence rate of Dose Limiting Toxicity (DLT) within the first cycle [ Time Frame: Up to cycle 1 ]DLT is defined as the occurrence of any of the following adverse events (AE) or abnormal laboratory value (graded according to the NCI Common Terminology Criteria for AE (CTCAE) version 4.0), assessed as possibly, probably or definitively related to study drug/medication, occurring within the first cycle of study treatment: any Grade 4 thrombocytopenia or neutropenia lasting > 7 days; episcleritis, uveitis, or iritis of Grade 2 or higher, any Grade 4 toxicity, any Grade 3 toxicity EXCLUDING: nausea, vomiting, or diarrhea controlled by medical intervention within 72 hours, grade 3 rash in the absence of desquamation, no mucosal involvement, does not require steroids, and resolves to Grade 1 by the next scheduled dose of pembrolizumab, transient Grade 3 Aspartate Transaminase (AST) or Alanine Transaminase (ALT) elevation, defined as no more than 3 days with or without steroid use, discontinuation or delay of more than 2 weeks of any study drug/medication due to treatment-related AE.
- Recommended Phase II Dose (RP2D) of gemcitabine in combination with pembrolizumab [ Time Frame: Up to cycle 1 ]The RP2D will be decided by the internal committee taken into consideration the information obtained in the study and based on the DLT.
- Objective Response Rate (ORR) [ Time Frame: Through study treatment ]Tumor response will be assessed using RECIST 1.1 criteria. ORR is defined as the percentage of patients with a complete or partial response out of the Efficacy population
- Progression-Free Survival (PFS) [ Time Frame: Through study treatment ]PFS is defined as the time from enrollment to the first documented progressive disease, using RECIST version 1.1, or death from any cause, whichever occurs first.
- Clinical Benefit Rate (CBR) [ Time Frame: Through study treatment ]CBR is defined as complete response (CR), partial response (PR), or stable disease (SD) ≥ 24 weeks according to the RECIST version 1.1.
- Response Duration (RD) [ Time Frame: Through study treatment ]RD is defined as the time from the first documentation of objective tumor response (CR or PR) to the first documented progressive disease using RECIST version 1.1, or to death due to any cause, whichever occurs first.
- Overall Survival (OS). [ Time Frame: Through study treatment ]OS is defined as the time from the date of enrollment to the date of death from any cause.
- The Number of Participants Who Experienced Adverse Events (AE) [ Time Frame: Through study treatment up to 1 month after discontinuation ]Safety assessments to be performed at baseline and during the study: Vital signs assessments will include blood pressure, pulse and body temperature. A baseline standard 12-lead electrocardiogram (ECG) is mandatory. Safety laboratory assessments will be performed: hemoglobin, platelet count, White Blood Cell (WBC), Absolute Neutrophil Count (ANC) and Absolute Lymphocyte Count (ALC), albumin, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, serum creatinine, creatinine clearance (for patients with creatinine levels > 1.5 x ULN), glucose and urea, International Normalized Ratio (INR)/ Prothrombin time (PT) and activated partial thromboplastin time (aPTT), total or free triiodothyronine (T3 or FT3), free thyroxine (FT4) and Thyroid-stimulating hormone (TSH), Urinalysis. AEs will be graded according to NCI-CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 4.0.
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): NCT03025880
|Institut Català d'Oncologia. Hospital Universitario Germans Trias i Pujol|
|Badalona, Barcelona, Spain, 08916|
|Hospital Universitario de Canarias|
|La Laguna, Canarias, Spain, 38320|
|Hospital Universitario Virgen de la Arrixaca|
|El Palmar, Murcia, Spain, 30120|
|Clínica Universitaria de Navarra|
|Pamplona, Navarra, Spain, 31008|
|Centro Oncológico de Galicia|
|A Coruña, Spain, 15009|
|Hospital Universitario Ramón y Cajal|
|Madrid, Spain, 28034|
|Hospital Clínico Universitario San Carlos|
|Madrid, Spain, 28040|
|Hospital Universitario Virgen de la Macarena|
|Sevilla, Spain, 41009|
|Hospital Clínico Universitario de Zaragoza "Lozano Blesa"|
|Zaragoza, Spain, 50009|
|Study Director:||Study Director||Hospital Universitario Virgen Macarena|