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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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by Puma Biotechnology, Inc.
Sponsor:
Information provided by (Responsible Party):
Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier:
NCT01953926
First received: September 26, 2013
Last updated: September 29, 2016
Last verified: September 2016
  Purpose
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.

Condition Intervention Phase
Solid Tumors
Drug: Neratinib
Drug: Paclitaxel
Drug: Fulvestrant
Phase 2

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by Puma Biotechnology, Inc.:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 292
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)
Arms Assigned Interventions
Experimental: Neratinib monotherapy
Neratinib monotherapy in any HER2 mutated Cancers excluding Hormone positive breast cancers and bladder cancers
Drug: Neratinib
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
Drug: Neratinib
Neratinib 240 mg orally, once daily with food, continuously in 28 day cycles
Drug: 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
Drug: Neratinib
Neratinib 240 mg orally, once daily with food, continuously in 28 day cycles
Drug: 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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed cancers for which no curative therapy exists.
  • Documented HER2 mutation.

Exclusion Criteria:

  • Prior treatment with any pan-HER TKI (eg, lapatinib, afatinib, dacomitinib, neratinib).
  • Patients who are receiving any other anticancer agents.
  • Symptomatic or unstable brain metastases.
  • Women who are pregnant or breast-feeding.

Note: There are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01953926

Contacts
Contact: Puma Biotechnology, Clinical Operations (424) 248-6500 ClinicalTrials@pumabiotechnology.com

  Show 29 Study Locations
Sponsors and Collaborators
Puma Biotechnology, Inc.
  More Information

Responsible Party: Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier: NCT01953926     History of Changes
Other Study ID Numbers: PUMA-NER-5201  2013-002872-42 
Study First Received: September 26, 2013
Last Updated: September 29, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Puma Biotechnology, Inc.:
Neratinib
Fulvestrant
Breast
Gastroesophageal
Endometrial Ovarian Cancer
Biliary Tract
Solid tumors
HER2
Paclitaxel
Bladder/Urinary Tract

Additional relevant MeSH terms:
Paclitaxel
Fulvestrant
Albumin-Bound Paclitaxel
Estradiol
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Estrogens
Hormones

ClinicalTrials.gov processed this record on December 05, 2016