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Basket Study of Neratinib in Participants With Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations (SUMMIT)

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ClinicalTrials.gov Identifier: NCT01953926
Recruitment Status : Recruiting
First Posted : October 1, 2013
Last Update Posted : November 9, 2021
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 November 9, 2021
Actual Study Start Date  ICMJE September 30, 2013
Estimated Primary Completion Date March 30, 2022   (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 Basket Study of Neratinib in Participants With Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations
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, including HER2 mutant breast, HER2 mutant cervical, HER2 mutant salivary gland, and EGFR Exon 18 mutant Non-small cell lung cancers.

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.

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: 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, and lung cancers containing EGFR exon 18 mutations.
    Intervention: Drug: Neratinib
  • Experimental: Neratinib and Trastuzumab
    Neratinib and Trastuzumab in HER2 mutated (TNBC, HR-negative) breast cancers.
    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 September 30, 2022
Estimated Primary Completion Date March 30, 2022   (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) is excluded with the following exception: patients with EGFR exon 18 mutated NSCLC who may have received afatinib, osimertinib, or other pan HER or EGFR TKIs remain eligible
  • 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: Yes
Plan Description:

Puma Biotechnology is committed to sharing clinical trial data and information to help physicians and patients make informed treatment decisions, and to help qualified researchers advance scientific knowledge.

In accordance with legal and regulatory requirements, Puma publishes study protocol information and clinical study results on clinical trial registries, including ClinicalTrials.gov and EU Clinical Trials Register. Puma also publishes information about clinical studies in peer-reviewed scientific journals and shares data in scientific meetings.

Puma commits to safeguarding confidentiality and patient privacy throughout the clinical trial data and information sharing process. Any patient-level data will be anonymized to protect personally identifiable information.

Qualified researchers and study participants may submit requests for other study documentation and clinical trial data to clinicaltrials@pumabiotechnology.com for consideration.

Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Clinical study documents and clinical trial data may be requested by qualified researchers and study participants for studies that have been completed for at least 18 months, and for which the indication of the drug has been approved in the US and/or EU, as applicable. Requests will be accepted for up to 24 months after the criteria described in this section are met.
Access Criteria:

Requestors must provide organizational contact information; a detailed research plan, including outcomes; timeline for completion of the research; qualifications of the research team; funding source; and potential conflicts of interest.

Puma will not provide access to patient-level data if there is a reasonable likelihood that individual patients could be identified, or in cases where confidentiality or consent provisions prohibit transfer of data or information to third parties. Additionally, Puma will not disclose information that jeopardizes intellectual property rights or divulges confidential commercial information.

URL: https://pumabiotechnology.com/data_sharing_policy.html
Responsible Party Puma Biotechnology, Inc.
Study Sponsor  ICMJE Puma Biotechnology, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Senior Vice President Clinical Science and Pharmacology Puma Biotechnology, Inc.
PRS Account Puma Biotechnology, Inc.
Verification Date November 2021

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