A Phase 1/2 Study of HKI-272 (Neratinib) in Combination With Paclitaxel (Taxol) in Subjects With Solid Tumors and Breast Cancer

Breast Neoplasms Clinical Trial

Official title:

A Phase 1/2 Study of HKI-272 in Combination With Paclitaxel in Subjects With Solid Tumors and Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00445458
• Other study ID #: 3144A1-203 / B1891014
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 11, 2007
• Est. completion date: February 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 learn whether it is safe and effective to administer HKI-272 (neratinib) in combination with paclitaxel in patients with breast cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: February 7, 2018
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Inclusion criteria for both parts of clinical trial:

• Good performance status

• Normal ejection fraction

• Adequate cardiac, kidney, and liver function

• Adequate blood counts

• At least one measurable target lesion

• Negative pregnancy test for female subjects

Inclusion Criteria for Part 1 Only:

• Pathologically confirmed solid tumor not curable with available standard therapy

Inclusion Criteria for Part 2 Only:

• Pathologically confirmed breast cancer

• HER2 positive tumor

• Prior treatment with Herceptin

Exclusion Criteria:

Exclusion criteria for both parts of clinical trial:

• Major surgery, radiotherapy, chemotherapy or investigational agents within two weeks of treatment day 1

• Subjects with bone or skin as the only site of disease

• Active central nervous system metastases

• Significant cardiac disease or dysfunction

• Significant gastrointestinal disorder

• Inability or unwillingness to swallow HKI-272 capsules

• Prior exposure to HKI-272 or other HER2 targeted agents, except trastuzumab (Part 2 only). Prior lapatinib is permitted in arm B of part 2.

• Treatment with a taxane within 3 months of treatment day 1

• Grade 2 or greater motor or sensory neuropathy

• Pregnant or breast feeding women

• Known hypersensitivity to paclitaxel or Cremophor EL

• Prior treatment with anthracyclines with cumulative dose of >400 mg/m^2

• Any other cancer within 5 years with the exception of contralateral breast cancer, adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin

Exclusion Criteria for Part 2 Only:

• More than 1 (arm A) or 3 (arm B) prior cytotoxic chemotherapy regimen for metastatic disease

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Advanced Malignant Solid Tumors
• Breast Neoplasms

Intervention

Drug:
• HKI-272

• Paclitaxel

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet Unite du Chimiotherapie	Brussels
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	AZ Groeninge Campus Maria's Voorzienigheid (MV)	Kortrijk
Belgium	Oncologisch Centrum GZA - Location St Augustinus	Wilrijk
Canada	Princess Margaret Hospital University Health Network	Toronto	Ontario
China	Cancer Hospital, Chinese Academy of Medical Sciences	Beijing
China	Chinese People's Liberation Army General Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital of Chinese Academy of Medical Sciences	Beijing
China	The Hospital Affiliated Academy Military Medical Science, Chinese People's Liberation Army	Beijing	Beijing
China	Tianjin Cancer Hospital	TianJin	Tianjin
China	Tianjin Union Medicine Center Department of Oncology	Tianjin	Tianjin
Hong Kong	Department of Medicine, Queen Mary Hospital	Hong Kong
Hong Kong	Department of Surgery Queen Mary Hospital	Hong Kong
Hong Kong	UNIMED Medical Institute	Hong Kong
India	Birla Cancer Centre, S.M.S. Medical College & Hospital	Jaipur	Rajasthan
India	Tata Memorial Hospital	Mumbai	Parel
India	Jehangir Clinical Development Centre, Jehangir Hospital Premises	Pune	Maharashtra
India	M.M.F. Joshi Hospital & Ratna Memorial Hospital	Pune	Maharashtra
Korea, Republic of	Asan Medical Center, Division of Oncology, Department of Internal Medicine	Seoul
Korea, Republic of	Yonsei University Health System - Severance Hospital	Seoul
Poland	Wojewodzki Szpital Specjalistyczny im. Ludwika Rydygiera, Oddzial Onkologii	Krakow
Poland	Oddzial Chemioterapii Centrum Onkologii Ziemii Lubelskiej	Lublin
Ukraine	City Multifield Clinical Hospital #4 Department of chemotherapy, Dnipropetrovs'k State Medical Academy, Chair of Oncology and Medical Radiology	Dnipropetrovsk
Ukraine	State Oncological Regional Treatment and Diagnostic Center Department of chemotherapy	Lviv
United States	Boston University Medical Center	Boston	Massachusetts
United States	Moores UC San Diego Cancer Center	La Jolla	California
United States	Scripps, Clinic General	La Jolla	California
United States	Mid-Michigan Physicians-HOS Division	Lansing	Michigan
United States	Columbia University Medical Center	New York	New York
United States	Oncology Care Associates	Saint Joseph	Michigan
United States	CTRC at The University of Texas Health Science Center	San Antonio	Texas
United States	Sharp Memorial Hospital	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Puma Biotechnology, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  China,  Hong Kong,  India,  Korea, Republic of,  Poland,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicity Incidence of Neratinib in Combination With Paclitaxel	Dose Limiting Toxicity in subjects with solid tumors treated with neratinib, administered daily, in combination with paclitaxel 80 mg/m² IV on days 1, 8, and 15 of a 28 day cycle.	From first dose date through day 28
Primary	Maximum Tolerated Dose	Maximum Tolerated Dose (MTD) of neratinib, daily, in combination with paclitaxel 80 mg/m², intravenous at days 1, 8, and 15, associated with the dose limiting toxicity data.	From first dose date through day 28.
Primary	Objective Response Rate	Subjects with partial response (PR) or complete response (CR) with ERBB2 positive breast cancer treated at the maximum tolerated dose (MTD) of neratinib in combination with paclitaxel, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.0: CR, disappearance of all target lesions; PR, >=30% decrease in the sum of the longest diameter of target lesions; and no progressive disease (PD) for non-target lesions, and no new lesions.	From first dose date to progression or last tumor assessment, up to 140 weeks
Secondary	Maximum Plasma Concentration of Neratinib	Maximum plasma concentration of neratinib; after each dosing of neratinib on Cycle 1 of Day 15, blood samples taken at regular time points.	Samples taken at 0 hour and at 1, 2, 4, 6, 8, and 24 hours postdose on Day 15 of Cycle 1, and 1 predose sample on Day 1 in Cycle 1.
Secondary	Area Under the Concentration-time Curve 0-24	Area under the concentration-time curve of neratinib; after each dosing of neratinib on Cycle 1 of Day 15, blood samples taken at regular time points.	Samples taken at 0 hour and at 1, 2, 4, 6, 8, and 24 hours postdose on Day 15 of Cycle 1, and 1 predose sample on Day 1 in Cycle 1.