10. Metastatic Disease

10.1 Phase II Study of Yttrium Y 90 SMT 487 in Patients with Refractory Small Cell Lung Cancer or Metastatic Breast Cancer Expressing Somatostatin Receptor 

Objectives

I. Determine the tumor response rate of yttrium Y 90 SMT 487 in patients with refractory small cell lung cancer or advanced metastatic breast cancer expressing somatostatin receptor.

II. Determine the safety of this treatment regimen in these patients.

III. Determine the overall survival of these patients with this treatment regimen.

IV. Determine the quality of life in these patients with this treatment regimen.

V. Determine the frequency of tumors that are positive (3+ or 4+) for OctreoScan scintigraphy in this patient population.

Participation Criteria

• Diagnosis of metastatic breast cancer.
• No more than two prior chemotherapy regimens for metastatic disease.
• Measurable disease.
• Prior radiotherapy to measurable lesion allowed if progressed since treatment.
• No diffuse bone marrow involvement on OctreoScan scintigraphy.
• Positive for somatostatin receptors (grade 3 or 4) by Octreoscan scintigraphy.
• No unstable brain metastases within the past 6 months.

Protocol
Patients receive yttrium Y 90 SMT 487 IV over 10-15 minutes on day 1. Treatment repeats every 6-9 weeks for up to 3 courses in the absence of
unacceptable toxicity or disease progression.

Larry K. Kvols, Chair Principal Investigator
Ph: 813-972-8400, ext. 8286 H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida

10.2 Phase III Randomized Study of Low Molecular Weight Heparin (Dalteparin) Plus Standard Therapy Versus Standard Therapy Alone in Patients with Advanced Cancer 

Objectives

I. Compare the effect of low molecular weight heparin (dalteparin) plus standard therapy versus standard therapy alone on the overall survival rate of patients with advanced cancers.

II. Compare the toxic effects of these regimens and the effect on the quality of life of these patients.
III. Assess the incidence of symptomatic thrombotic events such as deep venous thrombosis (DVT), pulmonary embolus (PE), and clotted catheters in these patients.

Participation Criteria

• Histologically or cytologically proven breast, lung, colorectal, or prostate cancer that has failed prior chemotherapy or hormone therapy.
• No active CNS metastases.
• No concurrent anticoagulation therapy.

Randomization

Treatment continues for 1 year in the absence of disease progression and unacceptable toxicity.

Scott Okuno, Chair Principal Investigator
Ph: 507-284-2511 North Central Cancer Treatment Group Mayo Clinic Cancer Center Rochester, Minnesota

10.3 Phase III Randomized Study of Trastuzumab (Herceptin) Alone Followed By Paclitaxel Plus Trastuzumab Versus Upfront Combination of Trastuzumab and Paclitaxel in Women with HER2 Overexpressing Metastatic Breast Cancer

Objectives

I. Compare efficacy and toxicity of the sequential administration of trastuzumab (Herceptin) alone followed at disease progression by the combination of trastuzumab and paclitaxel versus the upfront combination of both drugs in women with HER2 overexpressing metastatic breast cancer.

II. Compare quality of life of these patients on these 2 regimens.

III. Investigate the predictive value of serum HER2/neu ECD levels on clinical outcome, the effects of trastuzumab on estrogen receptor, and the association of immunoprofiles of erbB-1, erbB-2, erbB-3, and erbB-4 with clinical outcome in this patient population.

Participation Criteria

• Histologically confirmed HER2 overexpressing metastatic breast carcinoma.
• Clinically or radiologically measurable or evaluable disease.
• Bidimensionally or unidimensionally measurable lesions.
• No cumulative dose of doxorubicin greater than 240 mg/m2.
• No cumulative dose of epirubicin greater than 360 mg/m2.
• No prior taxanes.

Randomization

Treatment continues in both arms until unacceptable toxicity or disease progression.

Aron Goldhirsch, Chair Principal Investigator
Ph: 39-02-574-894-39 Swiss Institute for Applied Cancer Research Istituto Europeo Di Oncologia Milano, Italy

10.4 Phase II Study of Exemestane and Goserelin in Premenopausal Women with Hormone Receptor Positive Metastatic Breast Cancer

Objectives

I. Determine the efficacy of exemestane and goserelin in premenopausal women with hormone receptor positive metastatic breast cancer after tamoxifen failure.

II. Determine the toxicity of this regimen in these patients.

III. Determine the hormonal profile of patients treated with this regimen.

IV. Determine the predictive value of HER-2, epidermal growth factor receptor, and estrogen 
receptor for response in patients treated with this regimen.

Participation Criteria

• Histologically or cytologically confirmed metastatic breast cancer that has failed prior tamoxifen therapy.
• Measurable disease
• Hormone receptor status:
  Estrogen or progesterone receptor positive at least 10 fmol/L by biochemical assay OR at least 10% of cells positive by immuno chemistry).
• Chemotherapy: No more than 2 prior chemotherapy regimens.
• No prior hormonal therapy for metastatic breast cancer.
• Concurrent bisphosphonates allowed for bone disease provided measurable disease in non-osseous sites.
• Menopausal status: Premenopausal defined as estradiol at least 30 pg/mL, follicle stimulating hormone less than 25 mIU/mL, and luteinizing hormone less than 15 mIU/mL.
• Performance status: ECOG 0-2

Protocol 

Patients receive oral exemestane daily on days 1-28 and goserelin subcutaneously on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Anne Hamilton Principal Investigator 
Ph: 212-263-6485 NYU School of Medicine's Kaplan Comprehensive Cancer Center New York, New York