OsteosarcomaPhase 2OCRNCT00743509
A Phase II Study of Oral Cyclophosphamide and Sirolimus (OCR) in Advanced Sarcoma
A Phase 2 study testing Cyclophosphamide and Sirolimus in people with Osteosarcoma, run by University of Michigan Rogel Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Osteosarcoma
- What is being tested?
- Cyclophosphamide and Sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2008to Sep 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Osteosarcoma
- Being tested
- Cyclophosphamide and Sirolimus
- Keywords
- sarcoma, Cyclophosphamide, Sirolimus, Progressive or recurrent, advanced (unresectable or metastatic) high-grade osteosarcoma, Ewing's or soft tissue sarcoma previously treated with chemotherapy.
- Medical subject headings
- Osteosarcoma, Sarcoma, Recurrence, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cyclophosphamide and SirolimusDrug
Also called Sirolimus (rapamycin, Rapamune)
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
| Study group | Role | What they receive |
|---|---|---|
| Oral Cyclophosphamide and Sirolimus (OCR) | Experimental | Sarcoma patients were given oral Cyclophosphamide and Sirolimus (OCR) in 28 day cycles. Receives: Drug: Cyclophosphamide and Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (1)
Median Overall Survival Time
Median overall duration of survival.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2008 (estimated)
- Study startAug 2008
- Primary completionApr 2010
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for OsteosarcomaStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Scott Schuetze, MD, PhD, Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00743509
- Sponsor's protocol ID
- UMCC 2008.049
- Acronym
- OCR
- Status last verified
- Aug 2015
- First submitted
- 27 Aug 2008
- Last updated
- 28 Sep 2015
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Oral Cyclophosphamide and Sirolimus (OCR) in Advanced Sarcoma
- ClinicalTrials.gov ID
- NCT00743509
- Acronym / sponsor ID
- OCR / UMCC 2008.049
- 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.
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- Aug 2008
- Primary completion
- Apr 2010 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 29 Aug 2008 (estimated)
- Results
- Posted 22 May 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Oral Cyclophosphamide and Sirolimus (OCR) | Experimental | Drug: Cyclophosphamide and SirolimusSarcoma patients were given oral Cyclophosphamide and Sirolimus (OCR) in 28 day cycles. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cyclophosphamide and SirolimusAlso: Sirolimus (rapamycin, Rapamune)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 | Drug | Oral Cyclophosphamide and Sirolimus (OCR) |
Primary outcome
Number of Patients Alive Without Disease Progression
Time frame: 6 months
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.
1 secondary outcome
Median Overall Survival Time
Time frame: 48 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott Schuetze, MD, PhD principal investigator
University of Michigan Rogel Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cyclophosphamide and Sirolimus in people with Osteosarcoma, run by University of Michigan Rogel Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 May 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients Alive Without Disease Progression (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2015.