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

Alternate Title

Combination Chemotherapy in Treating Women With Metastatic or Recurrent Breast Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed 18 and over Pharmaceutical / Industry SANDOZ-SMST-302 NCI-V96-0934

Objectives

I.  Compare progression-free survival in women with locally recurrent or 
metastatic breast cancer treated with tamoxifen plus octreotide pamoate 
long-acting release formulation vs. tamoxifen plus placebo.

II.  Compare the safety of these two regimens.

III.  Compare the objective tumor response rates, survival, and quality of 
life in these two treatment groups.

IV.  Compare the levels of insulin-like growth factor I (IGF-1) associated 
with these two regimens, and correlate IGF-1 suppression with progression-free 
survival, survival, and tumor response rate.

Entry Criteria

Disease Characteristics:

Histologically confirmed breast cancer that is metastatic or locally recurrent
and unsuitable for local therapy
  Cytologic or histologic confirmation of metastasis or recurrence required
  prior to entry if origin of tumor is questionable

  No rapidly progressing or immediately life-threatening disease

Hormone receptor status:
  Estrogen-receptor (ER) and/or progesterone-receptor (PR) positive on most
  recent assay
     ER and/or PR at least 10 fmol/mg if quantitative assay used
     Qualitative assay allowed
     Sandoz will perform assay if participating institution cannot

No disease progression during any prior nonablative hormonal adjuvant therapy

Measurable or evaluable lesion that is previously unirradiated
  New lesion in previously irradiated field (excluding bone) allowed
  Pleural effusion and ascites not considered measurable or evaluable
  Purely lytic bone lesion acceptable in patients with bone only metastasis
     Blastic or mixed (blastic and lytic) bone lesions not considered
     measurable

No known CNS metastasis (brain CT not required)

No serious secondary, malignancy-induced conditions (e.g., hypercalcemia)

Prior/Concurrent Therapy:

At least 4 weeks since any investigational drug

Biologic therapy:
  Not specified

Chemotherapy:
  At least 6 months since adjuvant or neoadjuvant chemotherapy and recovered

Endocrine therapy:
  See Disease Characteristics
  No prior cancer therapy with octreotide or other somatostatin analogue
     Prior octreotide allowed for chemotherapy-induced diarrhea
     Low-dose Octreoscan for imaging prior to protocol therapy allowed
  No prior nonablative hormonal therapy for advanced disease except tamoxifen
     if taken for less than 6 weeks
  At least 6 months since nonablative adjuvant hormonal therapy, e.g.:
     Tamoxifen          Toremifene       Estrogen
     Progestin          Anastrozole      Aminoglutethimide
     Corticosteroid     Androgen therapy
  At least 4 weeks since ablative hormonal therapy, e.g.:
     Goserelin          Leuprolide       Buserelin
     Other luteinizing hormone-releasing hormone agent
  At least 6 months since bilateral oophorectomy

Radiotherapy:
  See Disease Characteristics
  At least 12 months since radiotherapy and recovered except local irradiation
     of symptomatic bone disease allowed within 12 months

Surgery:
  Not specified

Other:
  No concurrent biphosphonates except to treat hypercalcemia considered
  unrelated to disease progression and for less than 4 weeks

Patient Characteristics:

Age:
  18 and over

Sex:
  Women only

Menopausal status:
  Pre- or postmenopausal

Performance status:
  Karnofsky greater than 50%

Life expectancy:
  At least 6 months

Hematopoietic:
  WBC at least 2,800/mm3
  Platelets at least 75,000/mm3 (untransfused)
  Hemoglobin at least 8.5 g/dL (5.3 mmoles/L) (untransfused)

Hepatic:
  Bilirubin less than 2 times normal
  AST/ALT less than 2 times normal (5 times normal with liver metastasis)
  Alkaline phosphatase less than 2 times normal (5 times normal with liver
     metastasis, no upper limit with bone metastasis)

Renal:
  Creatinine no greater than 1.95 mg/dL (177 micromoles/L)
  BUN no greater than 40 mg/dL (14.2 mmoles/L)
  Calcium less than 10% above normal

Other:
  No history of symptomatic gallstones unless patient has undergone
     cholecystectomy (asymptomatic cholelithiasis allowed)
  No other significant medical or surgical condition
  No requirement for medication that precludes safety and efficacy evaluations
  No prior or concurrent second malignancy except:
     In situ cervical cancer
     Nonmelanomatous skin cancer
  No pregnant or nursing women
     Negative pregnancy test required of fertile women
  Effective intrauterine or mechanical contraception required of fertile women
     No oral contraceptives
     Contraceptive implants removed prior to entry

Expected Enrollment

A maximum of 416 patients will be enrolled over 2 years on this multicenter 
study.  The study will close after 191 treatment failures occur.

Outline

This a randomized, double-blind, placebo-controlled study.  Patients are 
stratified by participating institution, dominant disease site, and prior 
tamoxifen therapy.

Patients are randomly assigned to receive intramuscular injections of either 
octreotide pamoate long-acting release formulation or placebo every 2 weeks 
for 4 doses, then every 4 weeks until disease progression or unacceptable 
toxicity intervenes.  Additionally, all patients receive daily oral tamoxifen, 
beginning after completion of octreotide or placebo.

Patients are followed every 6 months for up to 2 years.

Trial Contact Information

Trial Lead Organizations

Novartis Pharmaceuticals Corporation

Andrea C.M. Kay, MD, Protocol chair		Ph: 973-503-6793