High-Dose Consolidation With Escalating Doses of Melphalan and Thiotepa for Stage IV Breast Cancer


Phase 1
18 Years
65 Years
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

High-Dose Consolidation With Escalating Doses of Melphalan and Thiotepa for Stage IV Breast Cancer


OBJECTIVES: I. Determine the maximum tolerated dose of melphalan and thiopeta in patients
with recurrent or refractory solid tumors. II. Evaluate the overall survival and response
rate in these patients.

OUTLINE: This is a dose escalation study. Patients receive cyclophosphamide IV over 1 hour
on day 1 and paclitaxel IV over 4 or 24 hours on day 2, followed by daily filgrastim (G-CSF)
subcutaneously beginning on day 3 and continuing through day 7 or until WBCs are greater
than 100,000 cells/mm3. Peripheral blood stem cells (PBSC) or autologous bone marrow is
collected on days 5-7. At 30-50 days following mobilization, patients receive melphalan IV
over 15-60 minutes on days -5 and -4 and thiotepa IV over 2 hours on days -3 and -2,
followed by autologous bone marrow transplantation or PBSC infusion on day 0. Sequential
dose escalation of melphalan is followed by sequential dose escalation of thiotepa. Dose
escalation in cohorts of 5 patients each continues until the maximum tolerated dose (MTD) is
determined. The MTD is defined as the dose preceding that at which 2 of 4, 3 of 7, 4 of 11,
or 5 of 15 patients experience dose limiting toxicity. Patients are followed at 60 days and
at 12 months.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 4 years.

Inclusion Criteria


DISEASE CHARACTERISTICS: Histologically confirmed solid tumor Metastatic disease Recurrent
or refractory Pleural effusions allowed, if controlled Brain metastases allowed, if
symptoms controlled and negative MRI

PATIENT CHARACTERISTICS: Age: 18 to 65 Performance status: Karnofsky 70-100% Life
expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm3
Platelet count at least 100,000/mm3 No uncontrolled bleeding Hepatic: Bilirubin no greater
than 2.0 mg/dL SGOT and/or SGPT less than 3 times normal Renal: Creatinine no greater than
1.5 mg/dL Cardiovascular: Normal EKG Ejection fraction at least 45% Patients with abnormal
EKG, history of myocardial infarction, unstable angina, congestive heart failure, or prior
cumulative anthracycline dose of at least 250 mg/m2, must have a left ventricular ejection
fraction performed No congestive heart failure or uncontrolled hypertension Pulmonary:
DLCO greater than 60% No pneumonia No asthma, even if controlled Neurologic: No dementia
or altered mental status Other: No active infection (e.g., peritonitis, wound abscess) HIV
negative No prior cyclophosphamide induced hemorrhagic cystitis No serious concurrent
systemic disease (e.g., diabetes mellitus, hypothyroidism) No other active malignancies
Not pregnant Negative pregnancy test Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunotherapy Chemotherapy: No
other concurrent chemotherapy Endocrine therapy: Concurrent hormonal therapy allowed
Radiotherapy: No concurrent radiotherapy Surgery: At least 2 weeks since prior surgery and
recovered

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

William I. Bensinger, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Fred Hutchinson Cancer Research Center

Authority:

United States: Federal Government

Study ID:

1343.00

NCT ID:

NCT00003899

Start Date:

January 1999

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific

Name

Location
Fred Hutchinson Cancer Research Center Seattle, Washington  98109