A Phase II Study of Oral Cyclophosphamide and Sirolimus (OCR) in Advanced Sarcoma

NCT00743509 | Completed Phase 2 Results

• 1 other identifier: UMCC 2008.049
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this Phase II study will assess the effectiveness of the combination of oral cyclophosphamide and sirolimus in sarcoma patients with relapsed or widespread disease who cannot be cured by surgery, radiation or conventional chemotherapy.

Conditions

Osteosarcoma

Keywords

sarcoma; Cyclophosphamide; Sirolimus; Progressive or recurrent, advanced (unresectable or metastatic) high-grade osteosarcoma, Ewing's or soft tissue sarcoma previously treated with chemotherapy.

Outcome Measures

Primary Outcomes (1)

• Number of Patients Alive Without Disease Progression

  Patients who were evaluable for response to therapy, alive and without evidence of sarcoma disease progression. Target lesions followed were lesions that had progressed by World Health Organization (WHO) criteria. Disease progression is defined as a greater than or equal to 25% increase in the sum of the product of target lesions, or unequivocal progression of non-target lesions or the appearance of new tumor lesions \>10mm.

  6 months

Secondary Outcomes (1)

• Median Overall Survival Time

  48 weeks

Study Arms (1)

Oral Cyclophosphamide and Sirolimus (OCR)

EXPERIMENTAL

Sarcoma patients were given oral Cyclophosphamide and Sirolimus (OCR) in 28 day cycles.

Drug: Cyclophosphamide and Sirolimus

Interventions

Cyclophosphamide and Sirolimus DRUG

The dose of cyclophosphamide will start at 200 mg (4 tablets) per day on day 1 and will be taken for 7 days every other week of a 28 day cycle. Subjects will take 12 mg (12 tablets) of sirolimus on day 1 of treatment as a loading dose followed by 4 mg (4 tablets) daily continuously

Also known as: Sirolimus (rapamycin, Rapamune)

Oral Cyclophosphamide and Sirolimus (OCR)

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Progressive or recurrent, advanced (unresectable or metastatic) high-grade osteosarcoma, Ewing's or soft tissue sarcoma previously treated with chemotherapy.
• Bi-dimensionally measurable lesion(s) on cross-sectional radiography, such as computed tomography or magnetic resonance imaging, within 2 weeks of enrollment.
• ECOG/Zubrod performance score 0, 1 or 2.
• Total WBC \>3,000, neutrophil count \>1,000, platelet count \>100,000 within 2 weeks of enrollment.
• Serum creatinine \<2.0 times the institutional upper limit of normal (IULN) within 2 weeks of enrollment.
• AST and ALT \<2.5 times IULN (or if liver involvement by sarcoma \<5 times IULN) within 2 weeks of enrollment.
• Able to ingest oral medications.
• Sexually active women and men of childbearing potential must agree to use an effective method of birth control during the course of the study and for up to 1 month following the last dose of the study drug, in a manner such that risk of pregnancy is minimized. Surgical sterilization, oral contraceptive pills, intrauterine device, double barrier (e.g. condom and diaphragm or spermicidal agents) or abstinence are acceptable forms of birth control.
• Women of childbearing potential must have a negative pregnancy test within 2 weeks prior to treatment.
• Patient must be \>16 years of age at the time the consent document is signed by the patient.
• A paraffin block containing sarcoma, either from a previous surgery or recent biopsy, must be available for correlative studies. If a paraffin block containing sarcoma is not available, patients are required to undergo biopsy to obtain tissue for the correlative studies.

You may not qualify if:

• Active infection requiring antibiotic treatment.
• Diabetes mellitus not under good control (e.g. hemoglobin A1c \> 8% or fasting glucose \> 180 mg/dl) with oral agents or insulin.
• Prior treatment with mTOR inhibitor for sarcoma.
• Less than 3 weeks from prior treatment with chemotherapy to start of treatment with cyclophosphamide and sirolimus. Toxicities from prior chemotherapy (except alopecia) should be grade 1 or less before starting treatment with cyclophosphamide and sirolimus.
• Prior radiation less than two weeks since the administration of the last fraction of radiation therapy to the start of treatment. Patients must have recovered from grade 2 or higher radiation-associated toxicities to be eligible. All measurable lesions, which are being targeted, must be outside previously radiated fields or have documented progression at least 6 weeks after completion of radiation.
• Untreated or active CNS involvement by sarcoma.
• Active second malignancy other than carcinoma in situ. Patients with malignancy other than sarcoma in remission are eligible.
• Women who are pregnant or breastfeeding.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Osteosarcoma; Sarcoma; Recurrence; Neoplasm Metastasis

Interventions

Cyclophosphamide; Sirolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Macrolides; Lactones

Results Point of Contact

• Title: Scott Schuetze
• Organization: University of Michigan

scotschu@umich.edu

734-647-8925

Study Officials

• Scott Schuetze, MD, PhD

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2008
• First Posted: August 29, 2008
• Study Start: August 1, 2008
• Primary Completion: April 1, 2010
• Study Completion: September 1, 2012
• Last Updated: September 28, 2015
• Results First Posted: May 22, 2013

Record last verified: 2015-08

Locations

US (1)