Study Evaluating Neratinib (HKI-272) In Combination With Vinorelbine In Subjects With Solid Tumors And Metastatic Breast Cancer

NCT ID: NCT00706030

Last Updated: 2018-08-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-29
• Study Completion Date: 2018-06-07

Brief Summary

The purpose of this study is to identify the highest tolerable dose of neratinib (HKI-272) in combination with vinorelbine and to assess the safety of the combination of the two drugs as well as to obtain preliminary information on whether the combination of the two drugs has any effect on solid tumors.

The study will be conducted in two parts. In the first part, testing will be done on up to 12 subjects to determine the highest tolerable dose of HKI-272 and vinorelbine in patients with advanced solid tumors. In the second part of the study, approximately 60 additional subjects with metastatic ErbB-2-positive breast cancer, with no prior exposure to lapatinib, are planned to be added to better define the tolerability and preliminary activity of HKI-272 in combination with vinorelbine. Up to 20 additional subjects with ErbB-2-positive breast cancer with prior lapatinib exposure are also planned to be enrolled in part 2 for exploratory analyses.

Conditions

Breast Cancer; Advanced Malignant Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

neratinib 160 mg + vinorelbine

neratinib 160 mg tablets administered daily by mouth, vinorelbine 25 mg/m\^2 administered IV on day 1 and day 8 of 21 day cycle

Group Type: EXPERIMENTAL

neratinib

Intervention Type: DRUG

vinorelbine

Intervention Type: DRUG

neratinib 240 mg + vinorelbine

neratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m\^2 administered IV on day 1 and day 8 of 21 day cycle

Group Type: EXPERIMENTAL

neratinib

Intervention Type: DRUG

vinorelbine

Intervention Type: DRUG

neratinib 240 mg + vinorelbine, No Prior Lapatinib

neratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m\^2 administered IV on day 1 and day 8 of 21 day cycle

Group Type: EXPERIMENTAL

neratinib

Intervention Type: DRUG

vinorelbine

Intervention Type: DRUG

neratinib 240 mg + vinorelbine, Prior Lapatinib

neratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m\^2 administered IV on day 1 and day 8 of 21 day cycle

Group Type: EXPERIMENTAL

neratinib

Intervention Type: DRUG

vinorelbine

Intervention Type: DRUG

Interventions

neratinib

Intervention Type: DRUG

vinorelbine

Intervention Type: DRUG

Other Intervention Names

HKI-272; Nerlynx

Eligibility Criteria

Inclusion Criteria

• Confirmed pathologic diagnosis of a solid tumor that is not curable with available therapies for which HKI-272 plus vinorelbine is a reasonable treatment option (part 1 only) or Confirmed pathologic diagnosis of ErbB-2-positive breast cancer (current stage IV) in female subjects for which vinorelbine plus HKI-272 is a reasonable treatment option (part 2 only).
• At least 1 prior antineoplastic chemotherapy treatment regimen for metastatic disease and at least 1 prior treatment with a trastuzumab-containing regimen for at least 6 weeks, for metastatic disease or subject relapsing under adjuvant treatment (part 2 only).
• At least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST).

Exclusion Criteria

• More than 2 prior antineoplastic treatment regimens (excluding hormonotherapy) for metastatic disease. Subjects who relapsed under adjuvant treatment shouldn't have received more than one line of chemotherapy for metastatic disease (part 2 only).
• Prior treatment with vinorelbine for metastatic setting, or prior treatment with any ErbB-2 targeted agents except trastuzumab (part 2 only). Up to 20 subjects with ErbB-2-overexpressing metastatic breast cancer who have been previously exposed to lapatinib but are not refractory to lapatinib may be enrolled in part 2.
• Prior treatment with anthracyclines with a cumulative dose of doxorubicin of greater than 400 mg/m2, or of epirubicin dose of greater than 800 mg/m2, or the equivalent dose for other anthracyclines or derivatives (part 2 only).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Puma Biotechnology, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Puma

Role: STUDY_DIRECTOR

Biotechnology

Locations

Highlands Oncology Group

Fayetteville, Arkansas, United States

City of Hope National Medical Center

Duarte, California, United States

Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Columbia University Medical Center

New York, New York, United States

Hematology Oncology Associates of Rockland

Nyack, New York, United States

Albert Einstein Cancer Center

The Bronx, New York, United States

Carolinas Hematology-Oncology Associates

Charlotte, North Carolina, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

AZ Klina Brasschaat

Brasschaat, , Belgium

Institut Jules Bordet

Brussels, , Belgium

St.-Augustinus Hospital Oncology Department

Wilrijk, , Belgium

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

The Hospital Affiliated Academy Military Medical Science, Chinese People's Liberation Army

Beijing, Beijing Municipality, China

Chinese People's Liberation Army General Hospital

Beijing, Beijing Municipality, China

Tianjin Cancer Hospital

Tianjin, Tianjin Municipality, China

Centre Paul Papin

Angers, , France

Institut Paoli Calmette

Marseille, , France

Institut Curie, Département d'Oncologie Médicale

Paris, , France

Institut Claudius Regaud

Toulouse, , France

Queen Mary Hospital

Hong Kong, , Hong Kong

UNIMED Medical Institute

Hong Kong, , Hong Kong

Martini Ziekenhuis / Afdeling Interne Geneeskunde

Groningen, , Netherlands

Centrum Onkologii Ziemii Lubelskiej, Oddział Chemioterapii

Lublin, , Poland

Wojskowy Instytut Medyczny, Klinika Onkologii

Warsaw, , Poland

Centro Oncologico de Galicia

A Coruña, , Spain

Hospital Clinic i Provincial de Barcelona

Barcelona, , Spain

Hospital Arnau de Vilanova, Servicio de Oncologia Medica

Lleida, , Spain

Hospital 12 de Octubre, Servicio de Oncologia Medica

Madrid, , Spain

Onkologiska Kliniken Universitetssjukhuset i Lund

Lund, , Sweden

National Taiwan University Hospital

Taipei, , Taiwan

Broomfield Hospital

Chelmsford, Essex, United Kingdom

Southampton General Hospital

Southampton, Hampshire, United Kingdom

Christie NHS Foundation Trust

Manchester, Lancashire, United Kingdom

Velindre Cancer Centre

Cardiff, , United Kingdom

Guy's and St. Thomas' NHS Foundation Trust, Guy's Hospital

London, , United Kingdom

Countries

United States; Belgium; China; France; Hong Kong; Netherlands; Poland; Spain; Sweden; Taiwan; United Kingdom

References

Awada A, Dirix L, Manso Sanchez L, Xu B, Luu T, Dieras V, Hershman DL, Agrapart V, Ananthakrishnan R, Staroslawska E. Safety and efficacy of neratinib (HKI-272) plus vinorelbine in the treatment of patients with ErbB2-positive metastatic breast cancer pretreated with anti-HER2 therapy. Ann Oncol. 2013 Jan;24(1):109-16. doi: 10.1093/annonc/mds284. Epub 2012 Sep 11.

Reference Type: DERIVED

PMID: 22967996 (View on PubMed)

Other Identifiers

3144A1-2204 / B1891015

Identifier Type: -

Identifier Source: org_study_id