Gefitinib, Trastuzumab, and Docetaxel in Treating Patients With Metastatic Breast Cancer

NCT00086957 | Completed Phase 1 Results DMC

• 6 other identifiers: 03049P30CA033572CHNMC-03049ZENECA-1839US/0274ZENECA-IRUSIRES0012CDR0000371908
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 6

Brief Summary

RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining gefitinib and trastuzumab with docetaxel may kill more tumor cells. PURPOSE: This phase I/II trial is studying the best dose of docetaxel when given together with gefitinib and trastuzumab in treating patients with metastatic breast cancer.

Conditions

Breast Cancer

Keywords

stage IV breast cancer; male breast cancer; recurrent breast cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participants With at Least One Dose Limiting Toxicity in Phase I

  Dose Limiting Toxicity (DLT) defined as any treatment-related grade 3 or greater except for hematological toxicities which must be grade 4. Interstitial Lung Disease (ILD) related to treatment should be considered as a DLT regardless of the grade.

  4 weeks from start of treatment, up to 2 years

• Recommended Phase II Dose

  The maximum tolerated dose (MTD): subjects received gefitinib 250 mg orally daily, trastuzumab 6 mg/kg intravenously every 3 weeks (after an initial dose of 8 mg/kg with cycle 1), and docetaxel 75 mg/m\^2 intravenously every 3 weeks. This was to serve as the phase II dose if no dose-limiting toxicities (DLTs) occurred in the first three subjects. If one DLT occurred in the first three subjects, another three subjects where to be enrolled at this dose, whereas if two DLTs occurred in the first three subjects, the docetaxel dose was to be decreased to 60 mg/m\^2. The study would then be continued only if no more than one patient had a DLT at this dose. Once the dose of docetaxel was established, all further subjects were to be treated at the phase II MTD dose.

  4 weeks from start of treatment, up to 2 years

Secondary Outcomes (3)

• Progression-free Survival

  Until disease progression, up to 5 years.

• Objective Response Rate

  After 3 cycles of treatment, up to 2 years.

• Overall Survival

  Until death from any cause, up to 5 years.

Study Arms (1)

ZD1839, Trastuzumab and Docetaxel

EXPERIMENTAL

Biological: trastuzumab; Drug: docetaxel; Drug: gefitinib

Interventions

trastuzumab BIOLOGICAL

Cycle 1 loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks for subsequent cycles.

ZD1839, Trastuzumab and Docetaxel

docetaxel DRUG

75 mg/m2 every three weeks, or 60 mg/m2 every three weeks depending on study findings

ZD1839, Trastuzumab and Docetaxel

gefitinib DRUG

250 mg daily or 250 mg daily on days 2 through 14 depending on study findings

ZD1839, Trastuzumab and Docetaxel

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed adenocarcinoma of the breast * Metastatic disease * HER-2/neu overexpression (3+ by immunohistochemistry OR 2+ by fluorescence in situ hybridization) * Measurable or evaluable disease * Hormone receptor status: * Not specified PATIENT CHARACTERISTICS: Age * 18 and over Sex * Male or female Menopausal status * Not specified Performance status * ECOG 0-2 Life expectancy * Not specified Hematopoietic * Absolute granulocyte count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 Hepatic * AST and ALT \< 2.5 times upper limit of normal (ULN) (5.0 times ULN in the presence of liver metastases) * Bilirubin \< 1.5 times ULN * No unstable or uncompensated hepatic disease Renal * Creatinine \< 1.6 mg/dL * No unstable or uncompensated renal disease Cardiovascular * LVEF \> 45% by echocardiogram or MUGA * No prior New York Heart Association class I-IV heart disease * No prolonged PR interval or atrioventricular block on ECG * No unstable or uncompensated cardiac disease Pulmonary * No unstable or uncompensated respiratory disease * No clinically active interstitial lung disease * Patients who are asymptomatic and have chronic stable radiographic changes are allowed Immunologic * No autoimmune disorders * No conditions of immunosuppression * No severe hypersensitivity to taxane or gefitinib or any of its excipients Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No other prior or concurrent malignancy within the past 5 years except basal cell carcinoma or carcinoma in situ of the cervix * No other severe or uncontrolled systemic disease * No other acute or chronic medical condition that would preclude study participation * No other significant clinical disorder or laboratory finding that would preclude study participation * No psychiatric illness that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy * Prior adjuvant trastuzumab (Herceptin®) allowed if \> 6 months elapsed before disease recurrence * No prior trastuzumab for metastatic breast cancer * No prior monoclonal antibodies directed at the epidermal growth factor receptor (EGFR) Chemotherapy * Prior adjuvant chemotherapy (or as first-line therapy for metastatic breast cancer) allowed * Prior adjuvant taxane allowed if completed \> 6 months before diagnosis of metastatic breast cancer * No prior docetaxel for metastatic breast cancer Endocrine therapy * Prior adjuvant hormonal therapy (or as first-line therapy for metastatic breast cancer) allowed * No concurrent hormonal therapy * Concurrent steroids allowed provided dose is stable Radiotherapy * Not specified Surgery * Fully recovered from prior oncologic or other major surgery * No concurrent surgery within 7 days of gefitinib administration Other * Recovered from prior anticancer therapy (alopecia allowed) * More than 30 days since prior non-approved drug or investigational agent * No other prior EGFR-directed therapy (i.e., tyrosine kinase inhibitors) * No concurrent use of any of the following medications: * Phenytoin * Carbamazepine * Barbiturates * Rifampin * Hypericum perforatum (St. John's wort) * No other concurrent anticancer therapy * No concurrent cardioprotective drugs * No concurrent oral retinoids * Concurrent participation in the City of Hope indium-labeled trastuzumab imaging study allowed

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (6)

Tower Cancer Research Foundation

Beverly Hills, California, 90211-1850, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010-3000, United States

Location

Hematology Oncology Consultants-Hemet

Hemet, California, 92543, United States

Location

Breastlink Medical Group, Incorporated at Long Beach Memorial Medical Center

Long Beach, California, 90806, United States

Location

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, 90089-9181, United States

Location

City of Hope Medical Group

Pasadena, California, 91105, United States

Location

Related Publications (1)

• Somlo G, Koczywas M, Luu T, et al.: A phase I-II study of trastuzumab, gefitinib, and docetaxel as first line chemotherapy in patients with HER-2 overexpressing stage IV breast carcinoma. [Abstract] Breast Cancer Research and Treatment 94 (Suppl 1): A-2035, 2005.

  RESULT

MeSH Terms

Conditions

Breast Neoplasms; Breast Neoplasms, Male

Interventions

Trastuzumab; Docetaxel; Gefitinib

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; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Paul Frankel, Ph.D.
• Organization: City of Hope

pfrankel@coh.org

626-359-8111

Study Officials

• George Somlo, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2004
• First Posted: July 12, 2004
• Study Start: January 1, 2004
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: February 27, 2017
• Results First Posted: February 27, 2017

Record last verified: 2017-01

Locations

US (6)