Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	over 18	NCI	DMS-9224 NCI-T93-0026D, T93-0026

Objectives

I.  Evaluate the toxicity of escalating doses of interleukin-6 (IL-6) given 
with a constant dose of granulocyte colony stimulating factor (G-CSF) as a 
priming agent for peripheral blood stem cell (PBSC) acquisition prior to 
chemotherapy in patients with advanced breast cancer.

II.  Establish the maximum tolerated dose of IL-6 given with G-CSF.

III.  Assess whether G-CSF/IL-6 enhances the number of hematopoietic 
progenitor cells mobilized into peripheral blood as the dose of IL-6 is 
increased.

IV.  Assess the effects of IL-6 on numbers of platelet precursors in the 
peripheral blood and on megakaryocyte growth, and attempt to correlate these 
results with time to platelet engraftment.

V.  Assess the effects of escalating doses of IL-6 on the coagulation system 
and platelet activation.

VI.  Compare mean time to a platelet count above 20,000 between patients 
treated on this protocol and historical controls receiving only G-CSF pre- and 
post-PBSC infusion.

Entry Criteria

Disease Characteristics:

Breast cancer in one of the following categories:
  Stage IV disease, either hormone receptor-positive or -negative

  Stage IIIA/B disease unresectable at diagnosis

Objective response to an induction chemotherapy regimen required in patients
with measurable disease

Progressive disease after induction chemotherapy in patients with
nonmeasurable disease excludes

No brain metastases

Bilateral bone marrow aspirate and biopsy negative for malignancy

Prior/Concurrent Therapy:

Biologic therapy:
  At least 4 weeks since cytokines

Chemotherapy:
  See Disease Characteristics
  Prior adjuvant chemotherapy allowed
  Up to 2 prior chemotherapy regimens for advanced disease allowed
  At least 4 weeks since chemotherapy

Endocrine therapy:
  Not specified

Radiotherapy:
  No prior extensive pelvic irradiation

Surgery:
  Not specified

Patient Characteristics:

Age:
  Over 18

Sex:
  Not specified

Menopausal status:
  Not specified

Performance status:
  CALGB 0-1 (Karnofsky 80-100%)

Life expectancy:
  More than 2 months

Hematopoietic:
  AGC greater than 1,500
  Platelets greater than 100,000

Hepatic:
  Bilirubin less than 1.5 x normal
  SGOT less than 3 x normal
  No coagulation disorders

Renal:
  Creatinine less than 1.8 mg/dl OR
  Creatinine clearance at least 60 ml/min
  BUN less than 1.5 x normal

Cardiovascular:
  LVEF greater than 45%
  No uncontrolled or severe cardiovascular disease, e.g.:
     No recent MI
     No arrhythmia requiring therapy

Pulmonary:
  FVC, FEV1, and DLCO greater than 60% of predicted

Other:
  HIV and HBsAg seronegative
  No autoimmune disorders
  No requirement for steroid therapy
  No history of thrombosis
  No active, uncontrolled bacterial, viral, or fungal infection
  No active, uncontrolled or uncorrected duodenal ulcer
  No other serious medical illness that would limit survival to less than 2
     years
  No psychiatric condition that would preclude informed consent
  No previous or concurrent malignancy within 5 years except:
     Inactive nonmelanomatous skin cancer
     In situ carcinoma of the cervix

Expected Enrollment

Up to 30 patients will be accrued over approximately 10-15 months.

Outline

Patients are treated sequentially on Regimens A and B.

Regimen A:  Stem Cell Mobilization.  Interleukin-6 (Sandoz), IL-6, NSC-643497; 
Granulocyte Colony Stimulating Factor (Amgen), G-CSF, NSC-614629.

Regimen B:  3-Drug Combination Chemotherapy with Stem Cell Rescue and 
Hematopoietic Stimulation.  Cyclophosphamide, CTX, NSC-26271; Thiotepa, TSPA, 
NSC-6396; Carmustine, BCNU, NSC-409962; with Peripheral Blood Stem Cells, 
PBSC; and G-CSF.

Trial Contact Information

Trial Lead Organizations

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Letha Mills, MD, Protocol chair		Ph: 802-447-1836