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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier:
NCT00445458
First received: March 8, 2007
Last updated: January 31, 2013
Last verified: January 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Advanced Breast Cancer
Advanced Malignant Solid Tumors
Breast Neoplasms
 Drug: HKI-272
Drug: Paclitaxel
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of HKI-272 in Combination With Paclitaxel in Subjects With Solid Tumors and Breast Cancer

Resource links provided by NLM:

Drug Information available for: Paclitaxel
U.S. FDA Resources

Further study details as provided by Puma Biotechnology, Inc.:

Primary Outcome Measures:
  • Number of participants with adverse events [ Time Frame: At screening, then weekly (for HKI-272 + paclitaxel) or bimonthly (for HKI-272 alone) ] [ Designated as safety issue: Yes ]
  • Objective response rate [ Time Frame: At screening and then every 2 months throughout the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Observed maximum concentration of HKI-272 (neratinib) [ Time Frame: Prior to dosing on days 1 and 15 and 1, 2, 4, 6, 8, and 21-24 hourse after the dose on day 15 ] [ Designated as safety issue: No ]
  • Time of maximum concentration of HKI-272 (neratinib) [ Time Frame: Prior to dosing on days 1 and 15 and 1, 2, 4, 6, 8, and 21-24 hourse after the dose on day 15 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration versus time curve of HKI-272 (neratinib) [ Time Frame: Prior to dosing on days 1 and 15 and 1, 2, 4, 6, 8, and 21-24 hourse after the dose on day 15 ] [ Designated as safety issue: No ]

Enrollment: 115
Study Start Date: September 2007
Estimated Study Completion Date: December 2013
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1 - dose level 1
Subjects with solid tumors receiving HKI-272 (neratinib) in combination with paclitaxel
 Drug: HKI-272
neratinib 160 mg daily by mouth
Other Name: neratinib
Drug: Paclitaxel
paclitaxel 80 mg/m^2 weekly IV
Experimental: Part 1 - dose level 2
Subjects with solid tumors receiving HKI-272 (neratinib) in combination with paclitaxel
 Drug: HKI-272
neratinib 240 mg daily by mouth
Other Name: neratinib
Drug: Paclitaxel
paclitaxel 80 mg/m^2 weekly IV
Experimental: Part 2 - expanded MTD cohort, arm A
Subjects with metastatic breast cancer who have not received more than 1 prior cytotoxic chemotherapy treatment regimen for metastatic disease who will receive HKI-272 (neratinib) in combination with paclitaxel
 Drug: HKI-272
neratinib 240 mg daily by mouth
Other Name: neratinib
Drug: Paclitaxel
paclitaxel 80 mg/m^2 weekly IV
Experimental: Part 2 - expanded MTD cohort, arm B
Subjects with metastatic breast cancer who have not received more than 3 prior cytotoxic chemotherapy treatment regimen for metastatic disease who will receive HKI-272 (neratinib) in combination with paclitaxel
 Drug: HKI-272
neratinib 240 mg daily by mouth
Other Name: neratinib
Drug: Paclitaxel
paclitaxel 80 mg/m^2 weekly IV

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00445458

  Show 36 Study Locations
Sponsors and Collaborators
Puma Biotechnology, Inc.
Investigators
Study Director: Puma Biotechnology
  More Information

No publications provided

Responsible Party: Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier: NCT00445458     History of Changes
Other Study ID Numbers: 3144A1-203, B1891014
Study First Received: March 8, 2007
Last Updated: January 31, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Puma Biotechnology, Inc.:
cancer
HKI-272
neratinib
 paclitaxel
Taxol
breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Paclitaxel
Tubulin Modulators
 Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 16, 2013