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Neratinib HER Mutation Basket Study (SUMMIT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01953926
Recruitment Status : Recruiting
First Posted : October 1, 2013
Last Update Posted : April 24, 2020
Sponsor:
Information provided by (Responsible Party):
Puma Biotechnology, Inc.

Tracking Information
First Submitted Date  ICMJE September 26, 2013
First Posted Date  ICMJE October 1, 2013
Last Update Posted Date April 24, 2020
Actual Study Start Date  ICMJE September 30, 2013
Estimated Primary Completion Date September 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 21, 2020)
  • Confirmed Objective Response Rate (Breast, Cervical Cohorts) [ Time Frame: From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, up to 18 months ]
    Percentage of participants who are confirmed by independent central review to have achieved complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (HR+, HER2 negative metastatic breast cancer, and metastatic cervical cancer cohorts)
  • Objective Response Rate - First Tumor Assessment (Other Cohorts) [ Time Frame: From enrollment date to first Complete or Partial Response, whichever came earlier, up to 8 or 9 weeks ]
    Percentage of participants who achieve CR or PR per RECIST v1.1, or other defined response criteria, at the first scheduled tumor assessment (all other cohorts)
Original Primary Outcome Measures  ICMJE
 (submitted: September 26, 2013)
Objective Response Rate at 8 weeks (ORR8) [ Time Frame: 8 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 21, 2020)
  • Progression-Free Survival (PFS) [ Time Frame: From enrollment date until the date of first documented progression, or date of death from any cause, whichever came first, assessed up to 18 months ]
    Number of months between first dose date and the first date on which recurrence, progression, or death due to any cause, is documented, censored at the last tumor assessment or at the initiation of new anticancer therapy
  • Confirmed Objective Response Rate (Other Cohorts) [ Time Frame: From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, up to 18 months ]
    Percentage of participants who are confirmed by independent central review to have achieved CR or PR according to RECIST v1.1 (all other cohorts)
  • Objective Response Rate - First Tumor Assessment (Breast, Cervical Cohorts) [ Time Frame: From enrollment date to first Complete or Partial Response, whichever came earlier, up to 8 or 9 weeks ]
    Percentage of participants who achieve CR or PR according to RECIST v1.1, or other defined response criteria, at the first scheduled tumor assessment (HR+, HER2 negative metastatic breast cancer, and metastatic cervical cancer cohorts)
  • Clinical Benefit Rate (CBR) [ Time Frame: From enrollment date to first documented response or stable disease ≥16, or ≥24 weeks for breast cancer, assessed up to 18 months ]
    Percentage of participants with CR + PR + stable disease ≥16, or ≥24 weeks for breast cancer, from the date of enrollment
  • Duration of Response (DOR) [ Time Frame: From first response to first disease progression or death, assessed up to 18 months ]
    Time from which measurement criteria are met for confirmed overall response of CR or PR (whichever status is recorded first) until the first date of documented disease progression
  • Overall Survival (OS) [ Time Frame: From enrollment date to death, assessed up to two years ]
    Time from Cycle 1 Day 1 to death due to any cause
  • Incidence of Treatment-Emergent Adverse Events [ Time Frame: From first dose through 28 days after the last dose, assessed up to 18 months ]
    Treatment-emergent and serious adverse events that occurred on or after first dose of investigational product and up to 28 days after the last dose
Original Secondary Outcome Measures  ICMJE
 (submitted: September 26, 2013)
  • Overall Response Rate (ORR) [ Time Frame: Estimated 6 months ]
  • Progression-Free Survival (PFS) [ Time Frame: Estimated 18 months ]
  • Clinical Benefit Rate (CBR) [ Time Frame: 16 weeks ]
    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 ]
    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 ]
  • Safety (Adverse Events [AEs] and Serious Adverse Events [SAEs]) [ Time Frame: From consent through 28 days following treatment completion (estimated 6 months) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neratinib HER Mutation Basket Study
Official Title  ICMJE An Open-Label, Phase 2 Basket Study of Neratinib in Patients With Solid Tumors With Somatic Activating HER Mutations
Brief Summary This is an open-label, multicenter, multinational, Phase 2 basket study exploring the efficacy and safety of neratinib as monotherapy or in combination with other therapies in participants with HER (EGFR, HER2) mutation-positive solid tumors.
Detailed Description

This is an open-label, multicenter, multinational, Phase 2 basket study exploring the efficacy and safety of neratinib as monotherapy or in combination with other therapies in participants with HER (EGFR, HER2) mutation-positive solid tumors. The study has a basket design and includes several cohorts, either defined by an actionable somatic mutation or by actionable mutation and tumor histology (for example HER2 mutant cervical cancer).

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 days after the last dose of neratinib and a survival follow-up period lasting for a maximum of 12 months for each participant after their last dose of neratinib or until initiation of additional anti-cancer therapy.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations
Intervention  ICMJE
  • Drug: Neratinib
    240 mg administered orally, once daily with food, continuously in 28 day cycles
    Other Name: Nerlynx
  • Drug: Paclitaxel
    80mg/m^2 administered IV on Days 1, 8, and 15 of every 4 week cycle
    Other Name: Taxol
  • Drug: Fulvestrant
    500 mg administered as two 5 mL injections on Days 1, 15, and 29; then once every 4 weeks thereafter month, then Day 1 of every 4 week cycle
    Other Name: Faslodex
  • Drug: Trastuzumab
    Initial dose of 8 mg/kg of trastuzumab administered IV on Day 1, followed by 6 mg/kg IV once every 3 weeks thereafter
    Other Name: Herceptin
Study Arms  ICMJE
  • Experimental: Neratinib monotherapy
    Neratinib monotherapy in HER2 mutated cancers including cervical, salivary gland, solid tumors (NOS) and lung cancers containing EGFR exon 18 mutations. Cohorts closed to enrollment in Amendment 6: gastroesophageal, biliary, ovarian, solid tumor (NOS) HER4 mutant, and fibrolamellar carcinoma.
    Intervention: Drug: Neratinib
  • Experimental: Neratinib and Paclitaxel
    Neratinib and Paclitaxel in HER2 mutated bladder/urinary tract cancers.
    Interventions:
    • Drug: Neratinib
    • Drug: Paclitaxel
  • Experimental: Neratinib and Trastuzumab
    Neratinib and Trastuzumab in HER2 mutated (TNBC, HR-negative) breast cancers. Cohorts closed to enrollment in Amendment 6: colorectal, lung cancer HER2 mutant.
    Interventions:
    • Drug: Neratinib
    • Drug: Trastuzumab
  • Experimental: Neratinib, Fulvestrant and Trastuzumab (Randomized)
    Neratinib, Fulvestrant and Trastuzumab or Fulvestrant and Trastuzumab or Fulvestrant alone in HER2 mutated (HR-positive with prior CDK4/6i) breast cancers.
    Interventions:
    • Drug: Neratinib
    • Drug: Fulvestrant
    • Drug: Trastuzumab
  • Experimental: Neratinib, Fulvestrant and Trastuzumab (Non-Randomized)
    Neratinib, Fulvestrant and Trastuzumab in HER2 mutated (HR-positive with CDK4/6i naïve) breast cancers.
    Interventions:
    • Drug: Neratinib
    • Drug: Fulvestrant
    • Drug: Trastuzumab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 21, 2020)
650
Original Estimated Enrollment  ICMJE
 (submitted: September 26, 2013)
42
Estimated Study Completion Date  ICMJE March 30, 2022
Estimated Primary Completion Date September 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Provide written informed consent
  • Histologically confirmed cancers for which no curative therapy exists
  • Documented HER2 or EGFR exon 18 mutation
  • Participants must agree and commit to use appropriate methods of contraception as outlined in the protocol
  • At least one measurable lesion, defined by RECIST v1.1

Exclusion Criteria:

  • Participants harboring ineligible somatic HER2 mutations
  • Prior treatment with any HER2-directed tyrosine kinase inhibitor (e.g., lapatinib, afatinib, dacomitinib, neratinib, tucatinib, poziotinib)
  • Participants who are receiving any other anticancer agents
  • Symptomatic or unstable brain metastases
  • Women who are pregnant or breast-feeding

There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Puma Biotechnology, Inc. Clinical Operations Senior Director (424) 248-6500 ClinicalTrials@pumabiotechnology.com
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   Denmark,   Finland,   France,   Ireland,   Israel,   Italy,   Korea, Republic of,   Serbia,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01953926
Other Study ID Numbers  ICMJE PUMA-NER-5201
2013-002872-42 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Puma Biotechnology, Inc.
Study Sponsor  ICMJE Puma Biotechnology, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Chief Medical and Scientific Officer Puma Biotechnology, Inc.
PRS Account Puma Biotechnology, Inc.
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP