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

Puma Biotechnology

Status and phase: Completed; Phase 2; Phase 1

Conditions: Advanced Malignant Solid Tumors; Breast Neoplasms; Advanced Breast Cancer

Treatments: Drug: Paclitaxel; Drug: HKI-272

Study type: Interventional

Funder types: Industry

Identifiers

NCT00445458

3144A1-203 / B1891014

Details and patient eligibility

About

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.

Enrollment: 110 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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110 participants in 4 patient groups

HKI-272 dose level 1

Experimental group

Description:

Part 1: Subjects with solid tumors receiving HKI-272 (neratinib) 160 mg daily by mouth in combination with paclitaxel 80 mg/m\^2 weekly IV.

Treatment:

Drug: HKI-272

Drug: Paclitaxel

HKI-272 dose level 2

Experimental group

Description:

Part 1: Subjects with solid tumors receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m\^2 weekly IV.

Treatment:

Drug: HKI-272

Drug: Paclitaxel

HKI-272 expanded MTD cohort, arm A

Experimental group

Description:

Part 2: Subjects with metastatic breast cancer who have not received more than 1 prior cytotoxic chemotherapy treatment regimen for metastatic disease receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m\^2 weekly IV.

Treatment:

Drug: HKI-272

Drug: Paclitaxel

HKI-272 expanded MTD cohort, arm B

Experimental group

Description:

Part 2: Subjects with metastatic breast cancer who have not received more than 3 prior cytotoxic chemotherapy treatment regimen for metastatic disease receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m\^2 weekly IV.

Treatment:

Drug: HKI-272

Drug: Paclitaxel