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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.

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.

Condition or disease Intervention/treatment Phase
Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations Drug: Neratinib Drug: Paclitaxel Drug: Fulvestrant Drug: Trastuzumab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 650 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Phase 2 Basket Study of Neratinib in Patients With Solid Tumors With Somatic Activating HER Mutations
Actual Study Start Date : September 30, 2013
Estimated Primary Completion Date : September 30, 2021
Estimated Study Completion Date : March 30, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: Neratinib
240 mg administered orally, once daily with food, continuously in 28 day cycles
Other Name: Nerlynx

Experimental: Neratinib and Paclitaxel
Neratinib and Paclitaxel in HER2 mutated bladder/urinary tract cancers.
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

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.
Drug: Neratinib
240 mg administered orally, once daily with food, continuously in 28 day cycles
Other Name: Nerlynx

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

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.
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

Experimental: Neratinib, Fulvestrant and Trastuzumab (Non-Randomized)
Neratinib, Fulvestrant and Trastuzumab in HER2 mutated (HR-positive with CDK4/6i naïve) breast cancers.
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




Primary Outcome Measures :
  1. 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)

  2. 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)


Secondary Outcome Measures :
  1. 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

  2. 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)

  3. 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)

  4. 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

  5. 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

  6. 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

  7. 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



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01953926


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

Locations
Show Show 62 study locations
Sponsors and Collaborators
Puma Biotechnology, Inc.
Investigators
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Study Director: Chief Medical and Scientific Officer Puma Biotechnology, Inc.
Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier: NCT01953926    
Other Study ID Numbers: PUMA-NER-5201
2013-002872-42 ( EudraCT Number )
First Posted: October 1, 2013    Key Record Dates
Last Update Posted: April 24, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Puma Biotechnology, Inc.:
Neratinib
Nerlynx
Breast
Solid Tumors
Cancer
HER2 mutations
EGFR mutations
Bladder/Urinary Tract
Paclitaxel
Fulvestrant
Trastuzumab
Cervical
Salivary
Additional relevant MeSH terms:
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Paclitaxel
Trastuzumab
Fulvestrant
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs