Trastuzumab, Docetaxel, and Carboplatin in Treating Women With Stage II, Stage III, or Inflammatory Breast Cancer

A Phase II Trial of Taxotere, Carboplatin and Herceptin in Locally Advanced or Inflammatory Breast Cancer

RATIONALE: Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as docetaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving trastuzumab together with docetaxel and carboplatin may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving trastuzumab together with docetaxel and carboplatin works in treating women with stage II, stage III, or inflammatory breast cancer.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: carboplatin; Drug: docetaxel; Biological: herceptin; Procedure: conventional surgery; Procedure: radiation therapy

Detailed Description

OBJECTIVES:

Primary

• Determine the antitumor activity of trastuzumab (Herceptin^®), docetaxel, and carboplatin, as measured by tumor response rate, in women with previously untreated HER2/neu-positive stage IIB, IIIA, IIIB, or IIIC or inflammatory breast cancer.

Secondary

• Determine the pathological complete response in patients treated with this regimen.
• Determine the disease-free survival of patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.
• Determine pathologic and molecular markers for predicting efficacy of this regimen in these patients.

OUTLINE: This is a non-randomized, multicenter study.

• Course 1 (days 1-28): Patients receive trastuzumab (Herceptin^®) IV over 30-90 minutes on days 1, 8, 15, and 22 and docetaxel IV over 1 hour and carboplatin IV over 30-60 minutes on day 8.
• Course 2-6: Patients receive trastuzumab IV over 30 minutes on days 1, 8, and 15 during courses 2-5 and on days 1, 8, 15, and 22 during course 6. Patients also receive docetaxel IV over 1 hour and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 5 additional courses (6 courses total) in the absence of disease progression or unacceptable toxicity.

Three weeks after completion of course 6, patients undergo restaging. Patients with local operable disease undergo modified radical mastectomy or lumpectomy and axillary node dissection followed by radiotherapy. Patients also receive trastuzumab IV once every 3 weeks for up to 52 weeks of total treatment (including the 6 courses of trastuzumab, docetaxel, and carboplatin) in the absence of disease progression or unacceptable toxicity. Patients who do not have local operable disease continue to receive trastuzumab as above.

PROJECTED ACCRUAL: A total of 13-43 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • Central Jersey Oncology Center, PA - East Brunswick
    • Freehold, New Jersey, United States, 07728
      • CentraState Medical Center
    • Hamilton, New Jersey, United States, 08690
      • Cancer Institute of New Jersey at Hamilton
    • Montclair, New Jersey, United States, 07042
      • Mountainside Hospital Cancer Center
    • Morristown, New Jersey, United States, 07962-1956
      • Carol G. Simon Cancer Center at Morristown Memorial Hospital
    • New Brunswick, New Jersey, United States, 08903
      • Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
    • New Brunswick, New Jersey, United States, 08901-1780
      • Saint Peter's University Hospital
    • Newark, New Jersey, United States, 07103
      • UMDNJ University Hospital
    • Summit, New Jersey, United States, 07902-0220
      • Overlook Hospital

Participation Criteria

Eligibility Criteria

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

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer, meeting 1 of the following stage criteria:

  • Stage IIB (T3, N0)
  • Stage IIIA (N0-N2)
  • Stage IIIB (T4, N0-2)
  • Stage IIIC
  • Inflammatory breast cancer
• HER2/neu-positive disease by fluorescence in situ hybridization
• Biopsy-accessible tumor
• Measurable disease by physical examination or x-ray
• No stage IV disease

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female

Menopausal status

• Not specified

Performance status

• ECOG 0-2

Life expectancy

• At least 8 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Meets 1 of the following criteria:

  • SGOT and SGPT ≤ 5 times upper limit of normal (ULN) AND alkaline phosphatase normal
  • SGOT and SGPT ≤ 1.5 times ULN AND alkaline phosphatase ≤ 2.5 times ULN
  • SGOT and SGPT normal AND alkaline phosphatase ≤ 5 times ULN
• Bilirubin normal

Renal

• Creatinine normal
• No pre-existing clinically significant renal disease that is not related to the malignancy

Cardiovascular

• Ejection fraction ≥ 50% by MUGA
• No pre-existing clinically significant cardiac disease that is not related to the malignancy
• No history of congestive heart failure

Pulmonary

• No pre-existing clinically significant pulmonary disease that is not related to the malignancy

Gastrointestinal

• No severe malnutrition
• No intractable emesis

Neurologic

• No pre-existing clinically significant neurologic disease that is not related to the malignancy

• No peripheral neuropathy ≥ grade 2

  • No nerve damage from diabetes

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective non-hormonal contraception during and for 4 weeks after completion of study treatment
• No known allergic reaction to study drugs
• No active infection
• No other malignancy except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No other pre-existing clinically significant disease that is not related to the malignancy
• No other serious or significant medical condition that would preclude study participation
• No other contraindication to study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No other concurrent immunotherapy

Chemotherapy

• No prior chemotherapy for the malignancy
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent hormonal therapy for the malignancy

Radiotherapy

• No concurrent radiotherapy

Surgery

• No concurrent surgery for the malignancy

Other

• More than 2 weeks since prior and no concurrent herbal remedies or aspirin-containing products
• No other concurrent investigational or commercial agents or therapies for the malignancy

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: Docetaxel, Carboplatin and Trastuzumab; A total of six cycles of TCH [(Taxotere® (75 mg/m2) + Carboplatin (AUC = 6) + Herceptin® (2 mg/kg weekly after a 4 mg/kg load on Day 1)] will be administered every 3 weeks.Three weeks after receiving the sixth cycle of TCH, all patients will be restaged.; Those determined to have localized and operable disease (as determined by surgical consultation) will undergo a modified radical mastectomy or lumpectomy and axillary node dissection. After recovery from surgery, the patients will receive whole breast or chest wall irradiation (as determined by radiologist) with concurrent Herceptin® (6 mg/kg). Following radiation, patients will continue Herceptin® (6 mg/kg) every 3 weeks until they have been on study for a total of 52 weeks.; If patients are staged and are negative they will continue Herceptin® (6 mg/kg)every 3 weeks until they have been on study for a total of 52 weeks.

Drug: carboplatin; Drug: docetaxel; Other Names: Taxotere; Biological: herceptin; Other Names: trastuzumb; Procedure: conventional surgery; Modified radical mastectomy or lumpectomy and axillary node dissection; Procedure: radiation therapy; Whole breast or chest wall irradiation (as determined by radiologist)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Antitumor Activity as Measured by Response Rate	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Pathological Complete Response	5 years
Disease-free Survival	10 years
Pathologic and Molecular Markers for Predicting Efficacy	5 years

Collaborators and Investigators

• Sponsor: University of Medicine and Dentistry of New Jersey
• Collaborators: National Cancer Institute (NCI); Aventis Pharmaceuticals

Publications and helpful links

Helpful Links

• Clinical trial summary from the National Cancer Institute's PDQ® database

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: July 8, 2005
• First Submitted That Met QC Criteria: July 8, 2005
• First Posted (Estimate): July 11, 2005

Study Record Updates

• Last Update Posted (Estimate): November 20, 2013
• Last Update Submitted That Met QC Criteria: September 17, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: stage IIIA breast cancer; stage IIIB breast cancer; stage II breast cancer; stage IIIC breast cancer; inflammatory breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Inflammatory Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Docetaxel; Carboplatin; Trastuzumab
• Other Study ID Numbers: 040412;CDR0000433511; P30CA072720 (U.S. NIH Grant/Contract); CINJ-040412 (Other Identifier: Cancer Institute of New Jersey); 0220045191 (Other Identifier: UMDNJ-RWJMS IRB); CINJ-NJ1104 (Other Identifier: Cancer Institute of New Jersey)