An Open-label, Phase 2 Study of Neratinib in Patients With Solid Tumors With Somatic Human Epidermal Growth Factor Receptor (EGFR, HER2, HER3) Mutations or EGFR Gene Amplification
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-label, Multicenter, Multinational, Phase 2 Study Exploring the Efficacy and Safety of Neratinib Therapy in Patients With Solid Tumors With Activating HER2, HER3 or EGFR Mutations or With EGFR Gene Amplification.|
- Objective Response Rate at 8 weeks (ORR8) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]The primary objective of this study is to determine the objective response rate at 8 weeks (ORR8) following treatment with neratinib in patients with HER2 (ERBB2), HER3 (ERBB3) or EGFR mutation-positive solid tumors or with EGFR gene amplification.
- Overall Response Rate (ORR) [ Time Frame: Estimated 6 months ] [ Designated as safety issue: No ]Secondary Outcome Measure Description is to determine the best confirmed overall response rate (ORR) with neratinib in patients with HER2, HER3 or EGFR mutation-positive solid tumors or with EGFR gene amplification.
- Progression-free survival (PFS) [ Time Frame: Estimated 18 months ] [ Designated as safety issue: No ]
- Clinical Benefit Rate (CBR) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]Clinical benefit rate (CBR) is defined as the percentage of patients with complete response (CR) + partial response (PR) + stable disease (SD) ≥16 weeks from the date of enrollment
- Duration of Response (DOR) [ Time Frame: Estimated 1 year ] [ Designated as safety issue: No ]Duration of response (DOR) is defined as the time from which measurement criteria are met for CR or PR (whichever status is recorded first) until the first date of documented disease progression.
- Overall survival (OS) [ Time Frame: Estimated 2 years ] [ Designated as safety issue: No ]
- Safety (Adverse Events [AEs] and Serious Adverse Events [SAEs]) [ Time Frame: From consent through 28 days following treatment completion (estimated 6 months) ] [ Designated as safety issue: Yes ]
|Study Start Date:||September 2013|
|Estimated Study Completion Date:||December 2018|
|Estimated Primary Completion Date:||September 2017 (Final data collection date for primary outcome measure)|
Experimental: Neratinib monotherapy
Neratinib monotherapy in any HER2 mutated Cancers excluding Hormone positive breast cancers and bladder cancers
Neratinib 240 mg orally, once daily with food, continuously in 28 day cycles
Experimental: Neratinib and Paclitaxel
Neratinib and Paclitaxel in HER2 mutated bladder cancers
Neratinib 240 mg orally, once daily with food, continuously in 28 day cyclesDrug: Paclitaxel
80mg/m^2 IV on Days 1, 8, and 15 of every 4 week cycle
Experimental: Neratinib and Fulvestrant
Neratinib and Fulvestrant in HER2 mutated hormone positive breast cancers Interventions
Neratinib 240 mg orally, once daily with food, continuously in 28 day cyclesDrug: Fulvestrant
500 mg administered as two 5 mL injections on Days 1, 15 of the first month, then Day 1 of every 4 week cycle
This is an open-label, multicenter, multinational, Phase 2 study exploring the efficacy and safety of neratinib therapy in patients with solid tumors with activating HER2, HER3 or EGFR mutations or with EGFR gene amplification.
The trial will consist of a screening period, a treatment period, and an end of treatment visit occurring when neratinib is discontinued for any reason, a safety follow-up visit occurring 28 to 42 days after the last dose of neratinib and a survival follow-up period lasting for a maximum of 12 months for each patient after their last dose of neratinib or until initiation of additional anti -cancer therapy.
Treatment will consist of neratinib alone 240 mg daily in all HER2 mutated cancers excluding hormone positive breast cancers and bladder cancers, or neratinib 240 mg daily and paclitaxel 80 mg/m^2 IV on Days 1, 8, and 15 of every 4 week cycle in bladder cancers , or neratinib 240 mg daily and fulvestrant 500 mg on Days 1, 15 of the first month, then Day 1 of every 4 week cycle in hormone positive breast cancers.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01953926
|Contact: Puma Biotechnology, Clinical Operations||(424) 248-6500||ClinicalTrials@pumabiotechnology.com|
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