Pilot Study of Paclitaxel Plus Pembrolizumab in Metastatic HER2-Negative Breast Cancer
- Conditions
- Breast - FemaleMale Breast Cancer
- Interventions
- Registration Number
- NCT03018080
- Lead Sponsor
- Wake Forest University Health Sciences
- Brief Summary
The primary objective of this study is to assess the safety and feasibility of the following two regimens: Cohort A) phased regimen of pembrolizumab in which paclitaxel is followed by paclitaxel plus pembrolizumab and Cohort B) concurrent regimen of paclitaxel plus pembrolizumab. The primary safety objective is to evaluate the overall grade 3 or 4 treatment-related adverse event rate for each cohort and compare them to relevant historical controls.
- Detailed Description
This is an open-label randomized pilot research study to determine if the study drug, pembrolizumab, is safe to use in combination with a chemotherapy drug called paclitaxel. This study will have the following two regimens: Cohort A) phased regimen of pembrolizumab in which paclitaxel is followed by paclitaxel plus pembrolizumab and Cohort B) concurrent regimen of paclitaxel plus pembrolizumab. A total of 40 evaluable subjects will be enrolled over an enrollment period of 18-24 months. The study is planned to enroll approximately 20 evaluable subjects in each treatment cohort.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A (Phased Pembrolizumab Regimen) Pembrolizumab Paclitaxel will be given as an IV infusion over 60 minutes, on days 1 and 8 every 21 (+/- 3) days during Cycles 1 and 2. No pembrolizumab will be given during Cycles 1 and 2. Starting with cycle 3 and subsequent cycles, pembrolizumab will be given as an IV infusion over 30 minutes before paclitaxel on day 1 every 21 (+/- 3) days. Arm A (Phased Pembrolizumab Regimen) Paclitaxel Paclitaxel will be given as an IV infusion over 60 minutes, on days 1 and 8 every 21 (+/- 3) days during Cycles 1 and 2. No pembrolizumab will be given during Cycles 1 and 2. Starting with cycle 3 and subsequent cycles, pembrolizumab will be given as an IV infusion over 30 minutes before paclitaxel on day 1 every 21 (+/- 3) days. Arm B (Concurrent Pembrolizumab Regimen) Pembrolizumab Pembrolizumab will be given as an IV infusion on day 1 before paclitaxel every 21 (+/- 3) days. Paclitaxel will be given as an IV infusion over 60 minutes, on days 1 and 8 every 21 (+/- 3) days. Arm B (Concurrent Pembrolizumab Regimen) Paclitaxel Pembrolizumab will be given as an IV infusion on day 1 before paclitaxel every 21 (+/- 3) days. Paclitaxel will be given as an IV infusion over 60 minutes, on days 1 and 8 every 21 (+/- 3) days.
- Primary Outcome Measures
Name Time Method Number of Participants With at Least One Grade 3 or 4 Treatment-related Adverse Event From enrollment to at least 30 days following cessation of study treatment. The median time on treatment was 5.5 months. Grade 3 or 4 study treatment-related adverse events will be determined for each subject as a binary variable indicating whether or not the subject experienced at least one grade 3 or 4 study treatment-related adverse events according to the NCI Common Terminology for Adverse Events, version 4.0. An adverse event will be considered study treatment related if it is determined that the event is at least possibly related to either paclitaxel, pembrolizumab, or both.
- Secondary Outcome Measures
Name Time Method Number of Subjects With an Objective Response (Per RECIST V1.1) From enrollment to best response while on study treatment; subjects remained on treatment until disease progression or death or unacceptable toxicity (subjects were on treatment for a median of 5.5 months) Objective response was determined for each subject as a binary variable indicating whether or not the subject achieved a best overall response of complete response (CR) or partial response (PR) as determined by RECIST 1.1 response criteria. A CR is indicated by disappearance of all target and non target lesions. A PR is indicated by \>=30% decrease in sum of longest diameter of target lesions with baseline as reference.
Progression-free Survival (PFS) Per RECIST 1.1 From treatment start date to date of progression/death, or censored as described; assessed for approximately 2 years. PFS is defined as the duration of time from treatment start date to first occurrence of either progressive disease (PD) or death. PD must be objectively determined per RECIST 1.1 criteria, where progression date is date of last assessment that identified PD. If subject died without documented PD, progression date will be death date. For surviving subjects who do not have PD, PFS will be censored at the date of last disease assessment. For subjects who received subsequent anti-cancer therapy prior to documented PD, PFS will be censored at the date of last disease assessment prior to commencement of subsequent therapy. Subjects who have an initial PFS event immediately following 2 or more consecutive missed assessments will be censored at date of last assessment prior to missed assessments.
Overall Survival (OS) From date of treatment start to date of death, or censored as described; assessed for approximately 5 years. OS is defined as the duration from treatment start date to the date of death from any cause. Subjects who are alive or lost to follow up at the time of the analysis will be censored at the last known date they were alive.
Number of Subjects With Disease Control (Per RECIST V1.1) From enrollment to best response while on study treatment; subjects remained on treatment until disease progression or death or unacceptable toxicity (subjects were on treatment for a median of 5.5 months) Disease control was determined for each subject as a binary variable indicating whether or not the subject achieved a best overall response of complete response (CR), partial response (PR), or stable disease (SD) as determined by RECIST 1.1 response criteria. A CR is indicated by disappearance of all target and non target lesions. A PR is indicated by \>=30% decrease in sum of longest diameter of target lesions with baseline as reference. SD is indicated by neither sufficient shrinkage to qualify for PR nor sufficient growth from nadir (\>=20%) to indicate progression.
Duration of Response (DoR) From date of response to date of progression/death, or censored as described above; assessed for approximately 2 years. Duration of Response (DoR) is defined as the duration of time from the first assessment that determined a CR or PR to the date of the first occurrence of progressive disease or death. Progression events and the censoring mechanism for DoR will be the same as described for PFS. DoR will be determined for each subject using the RECIST 1.1 criteria.
Trial Locations
- Locations (1)
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States