A Phase I Study of OncoLAR® (Registered Trademark) (NSC 685403) With/Without Tamoxifen in Patients With Osteosarcoma

NCT00001436 | Completed Phase 1

• 2 other identifiers: 95011995-C-0119
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The suppression of IGF-I and growth hormone may significantly alter the pathobiology of osteosarcoma. SMS 201-955 pa LAR is a long acting analog of Somatostatin which inhibits the pituitary release of growth hormone, reducing levels of circulating IGF-I . Additional data on tamoxifen usage has also demonstrated a reduction in circulating IGF-I levels. The degree of suppression of IGF-I and growth hormone will be determined at two dose levels of SMS 291-955 pa LAR. Tamoxifen will be added to two of the cohorts to determine if the additive effects of tamoxifen and SMS 201-955 pa LAR will lead to additional reduction of circulating IGF-I and growth hormone levels. Arginine-stimulated GH tests to assess levels of growth hormone in the blood will be administered pre-treatment evaluation up to three times, one time on weeks 2, 8, 16, 28, 40, 52, and one month post last dose of SMS 201-955 pa LAR. The four cohorts for this study will receive 60 or 90 mg SMS 201-955 pa LAR injectable every four weeks for up to 52 weeks. Two of the cohorts will receive 10 mg Tamoxifen on a daily basis.

Conditions

Neoplasm Metastasis; Osteosarcoma

Keywords

Hormone Interactions; IGF-I; Metastatic; Pediatric; Recurrent

Interventions

OncoLAR® (Registered Trademark) DRUG

tamoxifen DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

Must have been diagnosed with osteosarcoma by the age of 25 years. Patient must have a biopsy proven osteosarcoma and either: a) active tumor with no available standard therapy options; b) metastatic osteosarcoma at diagnosis, has completed therapy and has no evidence of active disease; or, c) is status-post any surgery for recurrent osteosarcoma, either local or metastatic recurrence, and is free of disease by CT scan. Measurable disease not required. Patients with serum creatinine \&lte; 2.0 mg/dL or creatinine clearance \&gte; 40 ml/min per 1.73m(2) (if serum creatinine is \&gte; 2.0 mg/dL). Patients with normal thyroid function. Patients with total bilirubin, SGOT and SGPT \< twice the upper limit of normal. Patients with normal direct bilirubin only if total direct bilirubin is abnormal. Patients with bone marrow criteria: ANC\>1500/mm(3) and platelet count \>100,000/mm(3). Patients without a history of insulin-dependent diabetes mellitus or current insulin requirement. Fasting morning blood glucose \<150 mg/dL. Patients with ECOG performance status of 0, 1 or 2 and a life expectancy of at least 8 weeks. Patients not on chemotherapy or radiation therapy within the past 2 weeks and recovered from the acute side effects of prior anti-neoplastic therapy. Patients with documented negative HIV serology within the past 6 months. Post-menarcheal patients must have documented negative urine and serum pregnancy test (B-HCG); when indicated, patient must be willing to take oral contraceptives or other appropriate contraceptives to avoid pregnancy during the period of treatment. Patient, parent or guardian must give informed consent. No pregnant or lactating women. No women of child-bearing potential who are unable or unwilling to use appropriate contraceptives during the period of treatment. No patients with uncorrected hypothyroidism. No patients with insulin-dependent diabetes mellitus or fasting blood glucose \&gte; 150 mg/dL. No patients with HIV infection. No patients with a history of thromboembolic events who require prophylaxis for thromboembolic events with anticoagulants once entry into Cohort III has begun. Patients with a history of symptomatic gallbladder disease must have had a cholecystectomy.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Cancer Institute (NCI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Kappel CC, Velez-Yanguas MC, Hirschfeld S, Helman LJ. Human osteosarcoma cell lines are dependent on insulin-like growth factor I for in vitro growth. Cancer Res. 1994 May 15;54(10):2803-7.

  PMID: 8168113 BACKGROUND

• Pollak M, Sem AW, Richard M, Tetenes E, Bell R. Inhibition of metastatic behavior of murine osteosarcoma by hypophysectomy. J Natl Cancer Inst. 1992 Jun 17;84(12):966-71. doi: 10.1093/jnci/84.12.966.

  PMID: 1321252 BACKGROUND

• Malaab SA, Pollak MN, Goodyer CG. Direct effects of tamoxifen on growth hormone secretion by pituitary cells in vitro. Eur J Cancer. 1992;28A(4-5):788-93. doi: 10.1016/0959-8049(92)90116-j.

  PMID: 1355980 BACKGROUND

MeSH Terms

Conditions

Neoplasm Metastasis; Osteosarcoma; Recurrence

Interventions

Tamoxifen

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Sarcoma; Disease Attributes

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: December 10, 2002
• Study Start: May 1, 1995
• Study Completion: September 1, 2000
• Last Updated: March 4, 2008

Record last verified: 2000-04

Locations

US (1)