Clinical Trial - NCT01953926

Neratinib HER Mutation Basket Study

Recruiting

Sponsor: Puma Biotechnology, Inc.

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT01953926

Protocol Info

Short Description: Phase II of Neratinib in AST with EGFR, HER2 and HER3 mutations or EGFR Gene Amplification
Long Description: 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
MGH Status: Open
Sponsor: Puma Biotechnology
Disease Program: Phase I

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.




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.
Condition Title Intervention Phase
Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations Neratinib Paclitaxel Fulvestrant Trastuzumab Phase 2
Study Type Interventional
Official Title An Open-Label, Phase 2 Basket Study of Neratinib in Patients With Solid Tumors With Somatic Activating HER Mutations

Primary Outcome Measures

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]


Secondary Outcome Measures

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

Duration of Response (DOR) [Time Frame: From first response to first disease progression or death, assessed up to 18 months] [Designated as safety issue: ]

Overall Survival (OS) [Time Frame: From enrollment date to death, assessed up to two years] [Designated as safety issue: ]

Incidence of Treatment-Emergent Adverse Events [Time Frame: From first dose through 28 days after the last dose, assessed up to 18 months] [Designated as safety issue: ]

Estimated Enrollment: 650
Study Start Date: September 2013
Estimated Study Completion Date: March 2022
Estimated Primary Completion Date: September 2021
Arms Assigned Interventions

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.

Experimental:Neratinib and Paclitaxel

Neratinib and Paclitaxel in HER2 mutated bladder/urinary tract cancers.
Drug:Paclitaxel
80mg/m^2 administered IV on Days 1, 8, and 15 of every 4 week cycle

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: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

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.

Experimental:Neratinib, Fulvestrant and Trastuzumab (Non-Randomized)

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

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01953926

Locations

  • United States, Alabama
    • University of Alabama at Birmingham Birmingham, Alabama, United States, 35249
  • United States, Arizona
    • Mayo Clinic Arizona Phoenix, Arizona, United States, 85054
  • United States, California
    • City of Hope Duarte, California, United States, 91010
    • University of California, San Diego La Jolla, California, United States, 92093
    • University of Southern California Los Angeles, California, United States, 90089
    • University of California, Los Angeles Los Angeles, California, United States, 90095
    • Stanford Cancer Center Palo Alto, California, United States, 94304
    • UCSF Helen Diller Family Comprehensive Cancer Center San Francisco, California, United States, 94115
    • Kaiser Permanente NoCal (STRATA) Vallejo, California, United States, 94589
  • United States, Delaware
    • Christiana Care Health Services, Christiana Hospital Newark, Delaware, United States, 19718
  • United States, Florida
    • Mayo Clinic Florida Jacksonville, Florida, United States, 32224
    • University of Miami Miami, Florida, United States, 33136
  • United States, Georgia
    • Winship Cancer Institute, Emory University Atlanta, Georgia, United States, 30322
  • United States, Illinois
    • Northwestern University Chicago, Illinois, United States, 60611
  • United States, Louisiana
    • Ochsner Clinic Foundation New Orleans, Louisiana, United States, 70121
  • United States, Massachusetts
    • Dana Farber Cancer Institute Boston, Massachusetts, United States, 02215
  • United States, Michigan
    • University of Michigan Ann Arbor, Michigan, United States, 48109
  • United States, Minnesota
    • Mayo Clinic Rochester, Minnesota, United States, 55905
    • Metro Minnesota Community Oncology Research Consortium Saint Louis Park, Minnesota, United States, 55416
  • United States, Missouri
    • Washington University Saint Louis, Missouri, United States, 63110
  • United States, New Jersey
    • Rutgers Cancer Institute of New Jersey New Brunswick, New Jersey, United States, 08903
  • United States, New York
    • Roswell Park Comprehensive Cancer Center Buffalo, New York, United States, 14263
    • Memorial Sloan-Kettering Cancer Center New York, New York, United States, 10065
  • United States, Ohio
    • Kettering Medical Center Kettering, Ohio, United States, 45429
  • United States, Pennsylvania
    • UPMC Magee-Woman's Hospital, Women's Cancer Center Pittsburgh, Pennsylvania, United States, 15213
    • Abington Memorial Hospital, Asplundh Cancer Pavilion Willow Grove, Pennsylvania, United States, 19090
  • United States, South Carolina
    • Saint Francis Cancer Center-Bon Secours Greenville, South Carolina, United States, 29607
  • United States, Tennessee
    • The West Clinic Germantown, Tennessee, United States, 38138
    • Vanderbilt-Ingram Cancer Center Nashville, Tennessee, United States, 37232
  • United States, Texas
    • UT Southwestern Medical Center Dallas, Texas, United States, 75390
    • MD Anderson Cancer Center Houston, Texas, United States, 77030
  • United States, Wisconsin
    • Gundersen La Crosse, Wisconsin, United States, 54601
    • University of Wisconsin Carbone Cancer Center Madison, Wisconsin, United States, 53792
  • Australia, Victoria
    • Peter MacCallum Cancer Centre East Melbourne, Victoria, Australia, 8006
  • Belgium,
    • UZ Leuven Leuven, , Belgium, 3000
  • Canada, British Columbia
    • British Columbia Cancer Center Vancouver, British Columbia, Canada, V5Z 4E6
  • Denmark,
    • University Hospital, Rigshospitalet Kopenhagen, , Denmark, DK-2100
  • Finland,
    • Helsinki University Central Hospital Helsinki, , Finland, 00029
  • France, Ile De France
    • Institut Curie - Hopital Rene Huguenin Saint-Cloud, Ile De France, France, 92210
  • France, Paris
    • Institut Gustave Roussy Villejuif, Paris, France, 94800
  • France,
    • Centre Leon Berard Lyon, , France, 69393
  • Ireland, Cork
    • Cork University Hospital Wilton, Cork, Ireland, T12 DC4A
  • Ireland, Leinster
    • St. Vincent's University Hospital Dublin, Leinster, Ireland, D04 T6F4
  • Israel,
    • Hadassah Medical Center Jerusalem, , Israel, 911200
    • Davidoff Cancer Center, Rabin Medical Center Petah Tikva, , Israel, 49100
    • Kaplan Medical Center Rehovot, , Israel, 76100
    • Sourasky Medical Center Tel Aviv, , Israel, 64239
  • Italy,
    • Azienda Socio Sanitaria Territoriale di Cremona Cremona, , Italy, 26100
    • AOU Citta della Salute e della Scienza di Torino Torino, , Italy, 10126
  • Korea, Republic of, Seoul
    • Yonsei University Health System, Serverance Hospital Seodaemun-Gu, Seoul, Korea, Republic of, 120-752
  • Serbia,
    • Institute for Oncology and Radiology of Serbia Belgrade, , Serbia, 11000
  • Spain,
    • Hospital Universitario Quiron Dexeus Barcelona, , Spain, 08028
    • Hospital Universitario Vall d'Hebron Barcelona, , Spain, 08035
    • Hospital Universitari Clinic Barcelona Barcelona, , Spain, 08036
    • Hospital Clinico Universitario San Carlos Madrid, , Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz Madrid, , Spain, 28040
    • Hospital Universitario Madrid Sanchinarro (START Madrid) Madrid, , Spain, 28050
    • Hospital Universitario Quiron Madrid Madrid, , Spain, 28223
    • Instituto Valenciano de Oncologia Valencia, , Spain, 46009
    • Hospital Clinico Universitario de Valencia Valencia, , Spain, 46010
  • United Kingdom,
    • University College London Hospitals NHS Foundation Trust London, , United Kingdom, NW1 2BU
    • Royal Free Hospital London, , United Kingdom, NW3 2QG

Sponsors and Collaborators

Puma Biotechnology, Inc.

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT01953926
Other Study ID Numbers: 2013-002872-42
Study First Received:
Last Updated:
Health Authority:

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:

Paclitaxel

Trastuzumab

Fulvestrant

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on October 14, 2020