Clinical Trials /

Neratinib HER Mutation Basket Study (SUMMIT)

NCT01953926

Description:

This is an open-label, non-randomized, multicenter, multinational, Phase 2 study exploring the efficacy and safety of neratinib as monotherapy or in combination with other therapies in patients with ERBB mutation-positive or EGFR gene-amplified solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Neratinib HER Mutation Basket Study (SUMMIT)
  • Official Title: 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.

Clinical Trial IDs

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

Conditions

  • Malignant Solid Tumor
  • Fibrolamellar Carcinoma

Interventions

DrugSynonymsArms
NeratinibNerlynxNeratinib monotherapy
PaclitaxelNeratinib and Paclitaxel
FulvestrantNeratinib, Fulvestrant and Trastuzumab
TrastuzumabNeratinib and Trastuzumab

Purpose

This is an open-label, non-randomized, multicenter, multinational, Phase 2 study exploring the efficacy and safety of neratinib as monotherapy or in combination with other therapies in patients with ERBB mutation-positive or EGFR gene-amplified solid tumors.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Neratinib monotherapyExperimentalNeratinib monotherapy in HER2 mutated cancers excluding colon cancer, lung cancer, breast cancer and bladder cancer, HER4 mutated cancer and in lung cancer containing EGFR exon 18 mutations, and fibrolamellar carcinoma.
  • Neratinib
Neratinib and PaclitaxelExperimentalNeratinib and Paclitaxel in HER2 mutated bladder cancers.
  • Neratinib
  • Paclitaxel
Neratinib, Fulvestrant and TrastuzumabExperimentalNeratinib, Fulvestrant and Trastuzumab in HER2 mutated hormone positive breast cancers.
  • Neratinib
  • Fulvestrant
Neratinib and TrastuzumabExperimentalNeratinib and Trastuzumab in ERBB2 mutated Hormone negative breast, lung, and colorectal cancers.
  • Neratinib
  • Trastuzumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed cancers for which no curative therapy exists.

          -  Documented HER2 mutation.

          -  Pediatric patients (at least 12 but less than 18 years of age at signing of informed
             consent) may be recruited in the Fibrolamellar Carcinoma cohort.

        Exclusion Criteria:

          -  Prior treatment with any pan-HER tyrosine kinase inhibitor (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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR first)
Time Frame:8 weeks
Safety Issue:
Description:Confirmed objective response rate 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

Measure:Objective Response Rate (ORR)
Time Frame:Estimated 6 months
Safety Issue:
Description:Confirmed objective response rate (ORR) according to RECIST v1.1 or other defined response criteria with neratinib monotherapy and combination therapy.
Measure:Progression-free survival (PFS)
Time Frame:Estimated 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 assessable evaluation or at the initiation of new anticancer therapy.
Measure:Clinical Benefit Rate (CBR)
Time Frame:16 weeks
Safety Issue:
Description:Percentage of patients with complete response (CR) + partial response (PR) + stable disease (SD) ≥16 weeks from the date of enrollment
Measure:Duration of Response (DOR)
Time Frame:Estimated 1 year
Safety Issue:
Description:Time from which measurement criteria are met for 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:Estimated 2 years
Safety Issue:
Description:Time from Cycle 1 Day 1 to death due to any cause.
Measure:Safety (Adverse Events and Serious Adverse Events)
Time Frame:From consent through 28 days following treatment completion (estimated 6 months)
Safety Issue:
Description:Safety profile and tolerability of neratinib monotherapy and combination therapy.

Details

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

Trial Keywords

  • Neratinib
  • Nerlynx
  • Breast
  • Gastroesophageal
  • Endometrial
  • Ovarian
  • Biliary Tract
  • Solid Tumors
  • Cancer
  • HER2
  • HER4
  • EGFR
  • Bladder/Urinary Tract
  • Paclitaxel
  • Fulvestrant
  • Trastuzumab
  • Fibrolamellar Carcinoma

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