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

Breast Cancer Clinical Trial

Official title:

A Phase 1/2 Study Of HKI-272 In Combination With Vinorelbine In Subjects With Solid Tumors And Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00706030
• Other study ID #: 3144A1-2204 / B1891015
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 29, 2008
• Est. completion date: June 7, 2018

Study information

• Verified date: June 2018
• Source: Puma Biotechnology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: June 7, 2018
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Advanced Malignant Solid Tumors
• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• neratinib

• vinorelbine

Locations

Country	Name	City	State
Belgium	AZ Klina Brasschaat	Brasschaat
Belgium	Institut Jules Bordet	Brussels
Belgium	St.-Augustinus Hospital Oncology Department	Wilrijk
China	Cancer Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing
China	Chinese People's Liberation Army General Hospital	Beijing	Beijing
China	The Hospital Affiliated Academy Military Medical Science, Chinese People's Liberation Army	Beijing	Beijing
China	Tianjin Cancer Hospital	TianJin	Tianjin
France	Centre Paul Papin	Angers
France	Institut Paoli Calmette	Marseille
France	Institut Curie, Département d'Oncologie Médicale	Paris
France	Institut Claudius Regaud	Toulouse
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	UNIMED Medical Institute	Hong Kong
Netherlands	Martini Ziekenhuis / Afdeling Interne Geneeskunde	Groningen
Poland	Centrum Onkologii Ziemii Lubelskiej, Oddzial Chemioterapii	Lublin
Poland	Wojskowy Instytut Medyczny, Klinika Onkologii	Warszawa
Spain	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
Sweden	Onkologiska Kliniken Universitetssjukhuset i Lund	Lund
Taiwan	National Taiwan University Hospital	Taipei
United Kingdom	Velindre Cancer Centre	Cardiff
United Kingdom	Broomfield Hospital	Chelmsford	Essex
United Kingdom	Guy's and St. Thomas' NHS Foundation Trust, Guy's Hospital	London
United Kingdom	Christie NHS Foundation Trust	Manchester	Lancashire
United Kingdom	Southampton General Hospital	Southampton	Hampshire
United States	Albert Einstein Cancer Center	Bronx	New York
United States	Carolinas Hematology-Oncology Associates	Charlotte	North Carolina
United States	City of Hope National Medical Center	Duarte	California
United States	Highlands Oncology Group	Fayetteville	Arkansas
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	Fox Chase Cancer Center	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Puma Biotechnology, Inc.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate	Overall Response Rate (ORR), subjects with CR or PR by independent review in subjects with ErbB-2-positive breast cancer treated at the MTD of neratinib in combination with vinorelbine per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions.	From first dose date to progression or last tumor assessment, up to four years and six months.
Primary	Maximum Tolerated Dose	Maximum Tolerated Dose (MTD) of Neratinib in combination with vinorelbine in subjects with advanced solid tumors.	From Day 1 to Day 21.
Secondary	Clinical Benefit Rate	Percentage of participants with partial response (PR) or complete response (CR) or stable disease > 24 weeks by independent assessment for subjects with ErbB-2-positive breast cancer treated at the MTD of neratinib in combination with vinorelbine, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions.	From first dose date to progression or last tumor assessment, up to four years and six months.
Secondary	Progression-Free Survival	Number of weeks between the date of the first dose of test article and the first date of disease recurrence or progression, or death due to any cause, was documented, censored at the last evaluation, investigator assessment. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (v1.0), as at least a 20% increase in the sum of the longest diameters (LD) of target lesions, taking as reference the nadir LD, meaning the smallest sum of the LDs recorded since the treatment started; or unequivocal progression of existing nontarget lesions; or the appearance of any new lesions.	From first dose date to progression or death, up to four years and six months.
Secondary	Duration Of Response	Duration of response for subjects who had complete or partial response from first response to disease progression, death or last assessment per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions.	From start date of response to first PD/death, up to four years and six months.