Clinical Trials /

Neratinib HER Mutation Basket Study

NCT01953926

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.

Related Conditions:
  • Bladder Carcinoma
  • Breast Carcinoma
  • Lung Carcinoma
  • Malignant Solid Tumor
  • Ureter Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Neratinib HER Mutation Basket Study
  • Official Title: An Open-Label, Phase 2 Basket Study of Neratinib in Patients With Solid Tumors With Somatic Activating HER Mutations

Clinical Trial IDs

  • ORG STUDY ID: PUMA-NER-5201
  • SECONDARY ID: 2013-002872-42
  • NCT ID: NCT01953926

Conditions

  • Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations

Interventions

DrugSynonymsArms
NeratinibNerlynxNeratinib and Paclitaxel
PaclitaxelTaxolNeratinib and Paclitaxel
FulvestrantFaslodexNeratinib, Fulvestrant and Trastuzumab (Non-Randomized)
TrastuzumabHerceptinNeratinib and Trastuzumab

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Neratinib monotherapyExperimentalNeratinib 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.
  • Neratinib
Neratinib and PaclitaxelExperimentalNeratinib and Paclitaxel in HER2 mutated bladder/urinary tract cancers.
  • Neratinib
  • Paclitaxel
Neratinib and TrastuzumabExperimentalNeratinib and Trastuzumab in HER2 mutated (TNBC, HR-negative) breast cancers. Cohorts closed to enrollment in Amendment 6: colorectal, lung cancer HER2 mutant.
  • Neratinib
  • Trastuzumab
Neratinib, Fulvestrant and Trastuzumab (Randomized)ExperimentalNeratinib, Fulvestrant and Trastuzumab or Fulvestrant and Trastuzumab or Fulvestrant alone in HER2 mutated (HR-positive with prior CDK4/6i) breast cancers.
  • Neratinib
  • Fulvestrant
  • Trastuzumab
Neratinib, Fulvestrant and Trastuzumab (Non-Randomized)ExperimentalNeratinib, Fulvestrant and Trastuzumab in HER2 mutated (HR-positive with CDK4/6i naïve) breast cancers.
  • Neratinib
  • Fulvestrant
  • Trastuzumab

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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)

Secondary Outcome Measures

Measure: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
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description:Percentage of participants who are confirmed by independent central review to have achieved CR or PR according to RECIST v1.1 (all other cohorts)
Measure: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
Safety Issue:
Description: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)
Measure: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
Safety Issue:
Description:Percentage of participants with CR + PR + stable disease ≥16, or ≥24 weeks for breast cancer, from the date of enrollment
Measure:Duration of Response (DOR)
Time Frame:From first response to first disease progression or death, assessed up to 18 months
Safety Issue:
Description: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
Measure:Overall Survival (OS)
Time Frame:From enrollment date to death, assessed up to two years
Safety Issue:
Description:Time from Cycle 1 Day 1 to death due to any cause
Measure:Incidence of Treatment-Emergent Adverse Events
Time Frame:From first dose through 28 days after the last dose, assessed up to 18 months
Safety Issue:
Description: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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Puma Biotechnology, Inc.

Trial Keywords

  • Neratinib
  • Nerlynx
  • Breast
  • Solid Tumors
  • Cancer
  • HER2 mutations
  • EGFR mutations
  • Bladder/Urinary Tract
  • Paclitaxel
  • Fulvestrant
  • Trastuzumab
  • Cervical
  • Salivary

Last Updated

April 21, 2020