Erlotinib Plus Docetaxel in Treating Patients With Stage IV or Recurrent Breast Cancer

A Phase II Study Of The Weekly Administration Of Docetaxel In Combination With The Epidermal Growth Factor Receptor Inhibitor OSI-774 In Recurrent And/Or Metastatic Breast Cancer

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib with docetaxel may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining erlotinib with docetaxel in treating patients who have stage IV or recurrent breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: docetaxel; Drug: erlotinib hydrochloride

Detailed Description

OBJECTIVES:

• Determine the antitumor effects of erlotinib and docetaxel, in terms of objective response, stabilization of disease, and progression-free survival, in patients with stage IV or recurrent breast cancer.
• Determine time to tumor progression in patients treated with this regimen.
• Compare time to tumor progression in patients who achieve disease stabilization or response after treatment with this regimen and continue to receive erlotinib versus patients who do not receive additional erlotinib.

OUTLINE: Patients receive docetaxel IV over 1 hour once weekly for 3 weeks and oral erlotinib once daily beginning on day 1. Treatment repeats every 4 weeks for a minimum of 6 courses in the absence of unacceptable toxicity or disease progression. Patients achieving maximal tumor response or stabilization of disease after 6 courses may continue to receive erlotinib alone until disease progression.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 12-14 months.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106-5065
      • Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed stage IV or recurrent adenocarcinoma of the breast
• Measurable disease
• Disease recurrence must not be within 1 year of receiving prior adjuvant docetaxel
• Stable brain metastases allowed

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Male or female

Menopausal status

• Not specified

Performance status

• ECOG (Eastern Cooperative Oncology Group) 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 6 months

Hematopoietic

• WBC(White Blood Count) at least 3,000/mm^3
• Platelet count at least 100,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Hemoglobin at least 8 g/dL

Hepatic

• Bilirubin normal
• AST(aspartate aminotransferase)/ALT(alanine aminotransferase) no greater than 2.5 times upper limit of normal

Renal

• Creatinine normal OR
• Creatinine clearance at least 60 mL/min
• No clinically significant proteinuria
• No significant impairment of renal function

Cardiovascular

• No New York Heart Association class III or IV heart disease
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No inadequately controlled hypertension

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception
• No prior severe hypersensitivity reaction to docetaxel or drugs formulated with polysorbate 80
• No other malignancy within the past 10 years except inactive nonmelanoma skin cancer, carcinoma in situ of the cervix, carcinoma in situ of the breast, or bilateral breast cancer
• No ongoing or active infection
• No peripheral neuropathy greater than grade 1
• No other concurrent uncontrolled medical condition that would preclude study participation
• No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior trastuzumab (Herceptin) allowed

Chemotherapy

• See Disease Characteristics
• No prior chemotherapy for recurrent or metastatic disease
• Prior adjuvant chemotherapy allowed

Endocrine therapy

• Prior hormonal therapy allowed

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No other concurrent investigational agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Erlotinib Plus Docetaxel

Drug: docetaxel; Docetaxel IV infusion weekly for 3 weeks with a one-week break. One cycle is 4 weeks (28 days). Patients' actual weight will be used to calculate dose.; Other Names: Taxotere; RP 56976; NSC #628503; Drug: erlotinib hydrochloride; OSI-774 will be taken 1 hour before or 2 hours after meals. Cycle 1 will be administered at dose level -1.If no grade 3 or 4 toxicity occurs during cycle 1, then the patient may proceed to be treated at dose level 0 for the remaining chemotherapy cycles.; Other Names: Tarceva; CP-358; 774; USAN: erlotinib hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Response (Tumor Measurements)Per RECIST Criteria v. 2000	Response and progression will be evaluated in this study using the criteria by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria. Partial Response: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions. Progressive Disease: At least a 20% increase in the sum of the LD of target lesions. Stable Disease: Neither sufficient shrinkage nor sufficient increase.	after 6 course (6 months) of combination therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival(PFS)	Progression free survival was defined as time from the start of treatment to the date of cancer progression, or death, and censored at the date of last follow-up for those without disease progression and still alive. Stable disease is measured from the start of the treatment until progression, taking as reference the smallest measurements recorded since the treatment started. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.	3 years
Overall Survival as of 2008	Overall survival (OS) was defined as time from the start of treatment to death, and censored at the time of last assessment for survivors.	5 yrs

Collaborators and Investigators

• Sponsor: Paula Silverman, MD
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Paula Silverman, MD, Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: December 1, 2002
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: February 5, 2003
• First Submitted That Met QC Criteria: February 5, 2003
• First Posted (Estimate): February 6, 2003

Study Record Updates

• Last Update Posted (Estimate): February 17, 2016
• Last Update Submitted That Met QC Criteria: February 15, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: stage IV breast cancer; recurrent breast cancer; male breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protein Kinase Inhibitors; Docetaxel; Erlotinib Hydrochloride
• Other Study ID Numbers: CWRU1102; P30CA043703 (U.S. NIH Grant/Contract); 07-02-14M (Other Identifier: University Hospitals IRB); CASE-CWRU-1102 (Other Identifier: Case Comprehensive Cancer Center)