View Clinical Trial (Medical Research Study)
Sirolimus in Combination With Metronomic Therapy in Children With Recurrent and Refractory Solid Tumors: A Phase I Study
| City: |
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Atlanta |
| State: |
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Georgia |
| Zip Code: |
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30322 |
| Conditions: |
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Ewing's Sarcoma - Osteosarcoma - Astrocytoma - Atypical Teratoid/Rhabdoid Tumor - Ependymoma - Germ Cell Tumor - Glioma - Medulloblastoma - Rhabdoid Tumor - Retinoblastoma - Clear Cell Sarcoma - Renal Cell Carcinoma - Wilms Tumor - Hepatoblastoma - Neurob |
| Purpose: |
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The best treatment for recurrent cancers or those that do not respond to therapies is not
known. Typically, patients with these cancers receive a combination of cancer drugs
(chemotherapy), surgery, or radiation therapy. These treatments can prolong their life but
may not offer a long-term cure.
This study proposes using a drug called Sirolimus in combination with common chemotherapy
drugs to treat patients with recurrent and refractory solid tumors. Sirolimus has been found
to inhibit cell growth and to have anti-tumor activity in pediatric solid tumors in previous
studies and, therefore, has the potential to increase the effectiveness of the chemotherapy
drugs when given together.
This study wil investigate the highest dose of Sirolimus that can be given orally with other
oral chemotherapy drugs. Cohorts of 2 subjects will be started at the minimum dose. The dose
will be increased in the next 2 subjects as long as there were no major reactions in the
previous groups. This study will also seek to learn more about the side effects of sirolimus
when used in this combination and what effects the drug has on the white cells and the
immune system. Successful use of this drug will impact the cancer population greatly by
providing an increased chance of survival to those with resistant or recurrent cancers.
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| Study Summary: |
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Sirolimus, is a potent immunosuppressive drug that is approved for use in prevention against
allograft rejection following solid organ transplant. It has anti-tumor effects mainly by
blocking signals which drive cells from G1 to S phase during cell cycle through inhibition
of mTOR, thus inhibiting cell growth. Sirolimus, as well as other mTOR inhibitors, has
shown anti-tumor activity in pediatric solid tumor xenografts. Children with relapsed
and/or refractory solid tumors are in need of novel therapeutic approaches. One option for
these patients is the use of prolonged exposure to low dose antiangiogenic chemotherapy,
with agents such as etoposide and cyclophosphamide. In this phase I trial the feasibility
and optimal dosing for daily sirolimus, in combination with daily celecoxib, and low dose
etoposide alternating with cyclophosphamide, will be determined in children with relapsed
and refractory solid tumors. p70S6 kinase inhibition will be used as a surrogate for mTOR
inhibition. The potential immunosuppressive effect of sirolimus administered on this
schedule will be assessed by serial lymphocyte subsets and assessment of memory T cell
number.
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| Criteria: |
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Inclusion Criteria:
- must be <=30 years of age at time of study enrollment
- histologic verification of malignancy at original diagnosis or relapsis except in
patients with intrinsic brain stem tumors, optic pathway gliomas or patients wtih
pineal tumors and evaluations of serum or CSF alpha-fetoprotein or beta-HCG
- measurable or evaluable disease
- disease state must be one for which there is no known curative therapy
- Performance level >=50%
- Patients must have fully recovered from acute toxic effects of all prior
chemotherapy, immunotherapy or radiotherapy
- no evidence of acute graft vs. host disease and >=3 months since transplant
- organ function as defined in eligibility section of protocol
Exclusion Criteria:
- patients cannot be pregnant or breast-feeding
- patients must agree to use of an effective contraceptive method
- no growth factors that support platelet or white cell number or function for at least
7 days prior to enrollment
- patients receiving corticosteroids who have not been on a stable or decreasing dose
of corticosteroid for the prior 7 days are not eligible
- patients receiving any other investigational drugs
- patients receiving any other anti-cancer drugs
- patients who have an uncontrolled infection
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| NCT ID: |
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NCT01331135 |
| Primary Contact: |
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Principal Investigator
Howard Katzenstein, MD
Children's Healthcare of Atlanta
Sindy Midoro
Phone: 404-785-1441
Email: sindy.midoro@choa.org
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| Backup Contact: |
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Email: jaclyn.smith@choa.org
Jaclyn Smith, MBA
Phone: 404-785-0692
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| Location Contact: |
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Atlanta, Georgia 30322
United States
Sindy Midoro
Phone: 404-785-1441
Email: sindy.midoro@choa.org
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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June 18, 2013 |
| Modifications to this listing: |
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