Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Brain Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any - 30 |
| Updated: | 5/18/2018 |
| Start Date: | April 2011 |
| End Date: | April 2021 |
Sirolimus in Combination With Metronomic Therapy in Children With Recurrent and Refractory Solid Tumors: A Phase I Study
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.
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.
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.
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.
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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