A Randomized, Double-Blind, Phase 2 Trial of Paclitaxel Plus Bevacizumab and Enzastaurin Versus Paclitaxel Plus Bevacizumab and Placebo for Locally Recurrent or Metastatic Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Enzastaurin
- Conditions
- Breast Cancer
- Sponsor
- Eli Lilly and Company
- Enrollment
- 2
- Locations
- 1
- Primary Endpoint
- Progression Free Survival (PFS)
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
Brief Summary
The purpose of this study is to determine efficacy and safety of paclitaxel, bevacizumab and enzastaurin versus paclitaxel, bevacizumab, and placebo in participants who are diagnosed with locally recurrent or metastatic breast cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Must have signed an inform consent document
- •Have histologic or cytologic diagnosis of breast cancer with evidence of unresectable locally recurrent or metastatic disease
- •Have not received any prior chemotherapy for locally recurrent or metastatic disease
- •Have not had adjuvant or neoadjuvant taxane therapy within 12 months prior to assignment to study treatment
- •Age 18 years or older at time of informed consent
Exclusion Criteria
- •Have any clinical evidence of central nervous system (CNS) metastases
- •Have a history of seizure
- •Have had a major surgical procedure within 4 weeks prior to assignment to study treatment
- •Have had a minor surgical procedure, placement of an access device, or fine needle aspiration within 7 days prior to assignment to study treatment
- •Have symptomatic peripheral vascular disease
Arms & Interventions
Enzastaurin + Bevacizumab + Paclitaxel
Participants randomized to this arm (Arm A) will receive enzastaurin, paclitaxel and bevacizumab until disease progression. Prior to randomization, a safety lead-in will be conducted in 6 participants who will be treated according to Arm A for 2 cycles (1 cycle = 28 days). Only after an acceptable safety analysis of the safety lead-in, will other participants be randomized to Phase 2 (either Arm A or Arm B). In Phase 2, participants from the safety lead-in will continue treatment according to Enzastaurin + Bevacizumab + Paclitaxel (Arm A).
Intervention: Enzastaurin
Enzastaurin + Bevacizumab + Paclitaxel
Participants randomized to this arm (Arm A) will receive enzastaurin, paclitaxel and bevacizumab until disease progression. Prior to randomization, a safety lead-in will be conducted in 6 participants who will be treated according to Arm A for 2 cycles (1 cycle = 28 days). Only after an acceptable safety analysis of the safety lead-in, will other participants be randomized to Phase 2 (either Arm A or Arm B). In Phase 2, participants from the safety lead-in will continue treatment according to Enzastaurin + Bevacizumab + Paclitaxel (Arm A).
Intervention: Bevacizumab
Enzastaurin + Bevacizumab + Paclitaxel
Participants randomized to this arm (Arm A) will receive enzastaurin, paclitaxel and bevacizumab until disease progression. Prior to randomization, a safety lead-in will be conducted in 6 participants who will be treated according to Arm A for 2 cycles (1 cycle = 28 days). Only after an acceptable safety analysis of the safety lead-in, will other participants be randomized to Phase 2 (either Arm A or Arm B). In Phase 2, participants from the safety lead-in will continue treatment according to Enzastaurin + Bevacizumab + Paclitaxel (Arm A).
Intervention: Paclitaxel
Bevacizumab + Paclitaxel + Placebo
Participants randomized to this arm (Arm B) will receive bevacizumab, paclitaxel and placebo until disease progression.
Intervention: Bevacizumab
Bevacizumab + Paclitaxel + Placebo
Participants randomized to this arm (Arm B) will receive bevacizumab, paclitaxel and placebo until disease progression.
Intervention: Paclitaxel
Bevacizumab + Paclitaxel + Placebo
Participants randomized to this arm (Arm B) will receive bevacizumab, paclitaxel and placebo until disease progression.
Intervention: Placebo
Outcomes
Primary Outcomes
Progression Free Survival (PFS)
Time Frame: Baseline to measured PD (up to 15 days)
PFS was defined as the time from the date of study enrollment to the first date of objectively determined progressive disease (PD) or death from any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST version 1.0). PD is ≥20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. For participants not known to have died and who did not have PD, PFS was censored at the date of the last progression-free assessment. For participants who received subsequent systemic anticancer therapy (after discontinuation from the study treatment) prior to disease progression or death, PFS was censored at the date of last progression-free assessment prior to the initiation of post-discontinuation systemic anticancer therapy. No participant completed a full cycle of therapy and thus no formal analysis was performed.
Secondary Outcomes
- Overall Response Rate (ORR)(Baseline to measured Progressive disease (up to 15 days))
- Number of Participants With Adverse Events (AEs) or Any Serious AEs (SAEs)(Baseline to study completion (Day 15) plus 30-day safety follow-up)