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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT00743509
First received: August 27, 2008
Last updated: April 4, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Osteosarcoma
Drug: Cyclophosphamide and Sirolimus
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Oral Cyclophosphamide and Sirolimus (OCR) in Advanced Sarcoma

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • Progression-free Survival [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Patients who were still alive for assessment of lesions as defined by the World Health Organization (WHO) scale after 12 cycles or 48 weeks


Enrollment: 49
Study Start Date: August 2008
Estimated Study Completion Date: December 2013
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oral Cyclophosphamide and Sirolimus (OCR)
Sarcoma patients were given oral Cyclophosphamide and Sirolimus (OCR) in 28 day cycles.
Drug: Cyclophosphamide and Sirolimus

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

Other Name: Sirolimus (rapamycin, Rapamune)

Detailed Description:

The purpose of this Phase II study you are being asked to participate in 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. Malignant connective tissue tumors of soft tissue and bone (sarcomas) are highly aggressive cancers. There are few available chemotherapy treatments that are active in treating sarcomas. Sarcomas that have metastasized (spread throughout the body) are usually fatal. There is a great need to identify new active drugs to treat metastatic or relapsed sarcomas. Low dose oral daily cyclophosphamide is an established chemotherapy regimen for treatment of malignant and autoimmune disease and is generally well tolerated. Sirolimus is approved for prevention of kidney rejection after transplantation. Temsirolimus, a form of sirolimus, is approved for the treatment of kidney cancer. Sirolimus combined with cyclophosphamide in animal models of sarcoma resulted in significant anti-tumor activity. Tumor and blood samples will be studied to look for known protein targets of the medication to help learn why certain subjects have a favorable response to the treatment.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00743509

Locations
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan Cancer Center
Investigators
Principal Investigator: Scott Schuetze, MD, PhD University of Michigan Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT00743509     History of Changes
Other Study ID Numbers: UMCC 2008.049
Study First Received: August 27, 2008
Results First Received: April 4, 2013
Last Updated: April 4, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Michigan Cancer Center:
sarcoma
Cyclophosphamide
Sirolimus
Progressive or recurrent, advanced (unresectable or metastatic) high-grade osteosarcoma, Ewing's or soft tissue sarcoma previously treated with chemotherapy.

Additional relevant MeSH terms:
Osteosarcoma
Sarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Cyclophosphamide
Sirolimus
Everolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents

ClinicalTrials.gov processed this record on August 28, 2014