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

Alternate Title

Octreotide With or Without Tamoxifen in Treating Patients With Osteosarcoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	25 and under (at time of diagnosis)	NCI	NCI-95-C-0119I NCI-T96-0047N, T96-0047

Objectives

I. Determine and compare the degree of suppression of circulating insulin-like 
growth factor I (IGF I) and arginine-stimulated growth hormone (GH) levels at 
each of two doses of octreotide pamoate long-acting release formulation (SMS 
201-995 pa LAR) in patients with localized, metastatic, or recurrent 
osteosarcoma.

II. Determine whether the addition of tamoxifen (TMX) to SMS 201-995 pa LAR 
leads to significant additional reduction in circulating IGF I and GH levels.

III. Describe the toxic effects of prolonged SMS 201-995 pa LAR administration.

IV. Assess the feasibility of developing a phase III study of SMS 201-995 pa 
LAR with or without TMX as an adjuvant in the treatment of osteosarcoma.

V. Evaluate the antitumor effect of SMS 201-995 pa LAR in patients who have 
measurable disease.

Entry Criteria

Disease Characteristics:

Biopsy proven osteosarcoma of poor prognosis, e.g.:
  Active tumor with no available standard therapy
  Inactive after therapy but metastatic at diagnosis
  Disease-free by CT after any surgery for local or metastatic recurrence

Prior/Concurrent Therapy:

Biologic therapy:
 Not specified

Chemotherapy:
 At least 2 weeks since prior chemotherapy and recovered
 No other concurrent antineoplastic therapy

Endocrine:
 Concurrent thyroid hormone replacement allowed
 No concurrent supplemental recombinant human growth hormone

Radiotherapy:
 At least 2 weeks since prior radiotherapy and recovered
 
Surgery:
 Recovered from any prior surgery
 Prior cholecystectomy for symptomatic gallbladder disease

Patient Characteristics:

Age:
 25 and under (at time of diagnosis)

Performance status:
 ECOG 0-2

Life expectancy:
 At least 8 weeks

Hematopoietic:
 Absolute neutrophil count greater than 1,500/mm3
 Platelet count greater than 100,000/mm3

Hepatic:
 Total bilirubin less than 2 times upper limit of normal (ULN) OR
 Direct bilirubin normal
 Glucose (fasting, morning blood) less than 150 mg/dL
 SGOT and SGPT less than 2 times ULN

Renal:
 Creatinine no greater than 2.0 mg/dL OR
 Creatinine clearance at least 40 mL/min

Cardiovascular:
 No history of thromboembolic events or requirement of anticoagulants for
  prophylaxis of thromboembolic events once entry into dose level 3 has
  begun

Other:
 Asymptomatic cholelithiasis allowed
 No uncorrected hypothyroidism
 No prior or concurrent insulin-dependent diabetes mellitus
 Negative HIV serology documented within past 6 months
 Not pregnant or nursing 
 Negative pregnancy test   
 Fertile patients must use effective contraception

Expected Enrollment

A total of 24 patients will be accrued over 3 years.  

Outline

This is a dose escalation study of octreotide pamoate. Patients are stratified 
according to gender and ethnicity.

Patients receive octreotide pamoate intramuscularly once every 4 weeks alone 
or in combination with oral tamoxifen given daily for 4 weeks. Courses repeat 
every 4 weeks for 1 year in the absence of disease progression or unacceptable 
toxicity.

Cohorts of 6 patients receive escalating doses of octreotide pamoate until the 
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose 
preceding that at which 2 of 6 patients experience dose limiting toxicity.

Patients are followed monthly for 6 months, at 9 months and 1 year, every 6 
months for 1 year, and then annually thereafter until disease progression or 
other therapy.

Mansky PJ, Liewehr DJ, Steinberg SM, et al.: Treatment of metastatic osteosarcoma with the somatostatin analog OncoLar: significant reduction of insulin-like growth factor-1 serum levels. J Pediatr Hematol Oncol 24 (6): 440-6, 2002 Aug-Sep.[PUBMED Abstract]

Mansky PJ, Liewehr DM, Steinberg SM, et al.: Treatment of Metastatic Osteosarcoma (OS) with the Somatostatin Analog Oncolar®: Reduction of IGF-1 and Growth Hormone (GH) Serum Levels. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-1488, 2001.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Lee Helman, MD, Protocol chair		Ph: 301-496-4257 Email: helmanl@nih.gov