A Phase 1/2 Study Of HKI-272 (Neratinib) in Combination With Trastuzumab (Herceptin) In Subjects With Advanced Breast Cancer

NCT00398567 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 3144A1-202 / B1891013
• Study Type: interventional
• Target: 45
• Locations: 4 countries
• Sites: 14

Brief Summary

The purpose of this study is to determine the safety and efficacy of HKI-272 (neratinib) in combination with trastuzumab in patients with advanced breast cancer.

Conditions

Advanced Breast Cancer

Keywords

HKI-272; neratinib; trastuzumab; breast cancer; Nerlynx; PB-272; HER2

Outcome Measures

Primary Outcomes (1)

• 16-week Progression-free Survival (PFS) Rate

  16-week progression-free survival (PFS) rate for subjects with advanced breast cancer who receive neratinib at the maximum tolerated dose (MTD) in combination with trastuzumab, evaluable population.

  From first dose date to progression status (PD or death) at 16-week

Secondary Outcomes (6)

• Objective Response Rate (ORR)

  From first dose date to progression or last tumor assessment, up to five and a half years.

• Duration of Response (DOR)

  From start date of response to first PD, assessed up to five and half years after the first subject was randomized

• Progression Free Survival (PFS)

  From first dose date to progression or death, assessed up to five and half years.

• Clinical Benefit Rate (CBR)

  From first dose date to progression or last tumor assessment, assessed up to five and half years.

• Area Under the Curve of Neratinib Concentration

  Prior to the first dose, and at hours 1, 2, 4, 6, 8 and 24 on days 22.

Study Arms (3)

Part 1 - dose level 1 (160 mg)

EXPERIMENTAL

All subjects receiving HKI-272 dose level 1 in combination with trastuzumab

Drug: HKI-272; Drug: trastuzumab

Part 1 - dose level 2 (240 mg)

EXPERIMENTAL

All subjects receiving HKI-272 dose level 2 in combination with trastuzumab

Drug: HKI-272; Drug: trastuzumab

Part 2 - expanded MTD cohort

EXPERIMENTAL

All subjects receiving HKI-272 in combination with trastuzumab

Drug: HKI-272; Drug: trastuzumab

Interventions

HKI-272 DRUG

HKI-272 by mouth

Also known as: neratinib

Part 1 - dose level 1 (160 mg); Part 1 - dose level 2 (240 mg); Part 2 - expanded MTD cohort

trastuzumab DRUG

trastuzumab 4 mg/kg IV as a loading dose followed by trastuzumab 2 mg/kg weekly thereafter

Also known as: Herceptin

Part 1 - dose level 1 (160 mg); Part 1 - dose level 2 (240 mg); Part 2 - expanded MTD cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologic diagnosis of breast cancer with current stage IIIB, IIIC or IV not curable by available therapy
• Progression following at least one Herceptin-containing cytotoxic chemotherapy regimen (neoadjuvant, adjuvant, or metastatic setting)
• HER2 positive breast cancer
• At least one measurable target lesion
• Adequate performance status
• Adequate cardiac, kidney, and liver function
• Adequate blood counts
• Willingness of all subjects who are not surgically sterile or post menopausal to use acceptable methods of birth control

You may not qualify if:

• More than 3 prior cytotoxic chemotherapy regimens for locally advanced or metastatic disease
• Major surgery, chemotherapy, radiotherapy, investigational agents, Herceptin or other cancer therapy within 2 weeks of treatment day 1
• Prior treatment with anthracyclines with cumulative dose of \>400 mg/m\^2
• Extensive visceral disease
• Active central nervous system metastases
• Pregnant or breast feeding women
• Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom
• Prior exposure to HKI-272 or other HER2 targeted agents (except Herceptin and Tykerb)
• Significant cardiac disease or dysfunction
• History of life-threatening hypersensitivity to Herceptin
• Inability or unwillingness to swallow HKI-272 capsules
• 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

Sponsors & Collaborators

• Puma Biotechnology, Inc.: lead

Study Sites (14)

City of Hope National Medical Center

Duarte, California, 91010-3000, United States

Location

LAC/USC Medical Center, USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

City of Hope National Medical Center

Pasadena, California, 91105, United States

Location

University of Maryland, University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Duke University, Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Chinese Nanjing Bayi Hospital

Nanjing, Jiangsu, 210002, China

Location

Tianjin Union Medicine Center

Tianjin, Tianjin Municipality, 300121, China

Location

Cancer Hospital, Academy of Med Science and Peking Union Med

Beijing, 100021, China

Location

307 Hospital of Chinese People's Liberation Army

Beijing, 100071, China

Location

Chinese PLA General Hospital

Beijing, 100853, China

Location

Institut Curie

Paris, 75005, France

Location

Centre Rene Gauducheau

Saint-Herblain, 44805, France

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

neratinib; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Senior Director, Clinical Operations
• Organization: Puma Biotechnology, Inc

clinicaltrials@pumabiotechnology.com

+1 424 248 6500

Study Officials

• Puma

  Biotechnology

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2006
• First Posted: November 10, 2006
• Study Start: April 4, 2007
• Primary Completion: July 31, 2009
• Study Completion: March 2, 2018
• Last Updated: July 24, 2018
• Results First Posted: April 13, 2018

Record last verified: 2018-06

Locations

US (6); CN (5); CH (1); FR (2)