Metronomic Therapy for Pediatric Patients With Solid Tumors at High Risk of Recurrence (Metronomic)
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|ClinicalTrials.gov Identifier: NCT02446431|
Recruitment Status : Recruiting
First Posted : May 18, 2015
Last Update Posted : May 18, 2015
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumor||Drug: Bevacizumab Drug: Cyclophosphamide Drug: Valproic Acid Drug: Temsirolimus||Early Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Metronomic Therapy for Pediatric Patients With Solid Tumors at High Risk of Recurrence: A Multi-Institutional Study|
|Study Start Date :||July 2014|
|Estimated Primary Completion Date :||July 2024|
|Estimated Study Completion Date :||July 2029|
Experimental: Metronomic Therapy
There is only one arm in this study. All subjects receive the same therapy for a period of 420 days (42 day cycles x 10 cycles).
Avastin is an anti-angiogenic therapy that disrupts a tumor's ability to grow by blocking the vascular endothelial growth factor protein, or VEGF. In tumors, cells produce excess VEGF therefore avastin's ability to block VEGF may prevent the growth of new blood vessels, including normal blood vessels and blood vessels that feed tumors. Avastin is not a chemotherapy; the purpose of Avastin is to block the blood supply that feeds the tumor. In this study Avastin is given IV at 10 mg/kg twice monthly for 10 cycles. This totals 20 administrations over a 1.12 year period.
Other Name: Avastin
Cyclophosphamide is an alkylating agent related to nitrogen mustard and is inactive until it is metabolized by P450 isoenzymes (CYP2B6, CYP2C9, and CYP3A4) in the liver to active compounds. The initial product is 4-hydroxycyclophosphamide (4-HC) which is in equilibrium with aldophosphamide which spontaneously releases acrolein to produce phosphoramide mustard. Phosphoramide mustard has been shown to produce interstrand DNA cross-link analogous to those produced by mechlorethamine. The plasma half-life ranges from 4.1 to 16 hours after IV administration. Cytoxan is taken orally as a 25 mg/m2 tablet daily for 14 days for 10 cycles (max dose =50mg). This totals 140 days over a 1.12 year period.
Other Name: Cytoxan
Drug: Valproic Acid
Valproic acid is a short chain fatty acid (VPA, 2-propylpetanoic acid) and approved for the treatment of epilepsy, bipolar disorders, migraines, and clinically used for schizophrenia. Currently, VPA is examined in numerous clinical trials for different leukemias and solid tumor entities. In addition to clinical assessment, the experimental examination of VPA as anti-cancer drug is ongoing. Although other mechanisms may also contribute to VPA-induced anti-cancer effects, inhibition of histone deacetylases appears to play a central role. Valproic acid is either given in suspension or tablet form 5 mg/kg, TID for 13 days for 10 cycles. This totals 130 days in a 1.12 year period.
Other Name: Depakote
Temsirolimus [an ester of the immunosuppressive compound sirolimus, (rapamycin, Rapamune®)] blocks cell cycle progression from the G1 to the S phase by binding to the intracellular cytoplasmic protein, FK506 binding protein (FKBP)12. This complex inhibits activity of the enzyme mTOR (mammalian target of rapamycin), inhibiting translation of several key proteins that regulate progression through the G1 phase in response to growth factors. Sirolimus, the major metabolite of temsirolimus, also binds to FKBP12. Given twice monthly at 25 mg/m2 via IV administration for 10 cycles totalling 20 administrations for 1.12 years.
Other Name: Torisel
- 5 year Event Free Survival [ Time Frame: Up to five years off therapy ]Imaging studies, laboratory studies, bone marrow exam
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to five years off therapy ]Imaging studies, laboratory studies, bone marrow exam
- Site(s) of relapse [ Time Frame: Up to five years off therapy ]Imaging studies, laboratory studies, bone marrow exam
- Composite Cost of Treatment [ Time Frame: Up to five years off therapy ]1) Day Hospital charges/costs, 2) physician fees, 3) laboratory/radiology cost/charges, 4) transfusions cost/charges, 5) drug costs/charges, 6) other supportive care charges/costs and 7) all charges/costs which directly result from consequences of this treatment protocol (i.e. need for hospitalization or Emergency Department visits) for 10 patients
- Fatigue scores on the PedsQL Fatigue Scale [ Time Frame: 420 days per subject ]PedsQL Fatigue Scale
- Pain scores on the Present Functioning Scale [ Time Frame: 420 days per subject ]Present Functioning Scale
- Quality of Life scores on the PedsQL Quality of Life Scale [ Time Frame: 420 days per subject ]PedsQL Quality of Life Scale
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02446431
|Contact: Ted Zwerdling, MDfirstname.lastname@example.org|
|Contact: Devin Murphy, MSWemail@example.com|
|United States, California|
|Miller Children's and Women's Hospital Long Beach||Recruiting|
|Long Beach, California, United States, 90806|
|Contact: Ted Zwerdling, MD 562-933-8600 firstname.lastname@example.org|
|Contact: Devin Murphy, MSW 562-933-8601 email@example.com|
|Children's Hospital Orange County||Recruiting|
|Orange, California, United States, 92868|
|Contact: Elyssa Rubin, MD 714-509-4348 firstname.lastname@example.org|
|Contact: Dorian Chan, RN,BSN,CCRC 714-509-7868 dchan@CHOC.ORG|
|Principal Investigator: Elyssa Rubin, MD|
|Principal Investigator:||Ted Zwerdling, MD||Miller Children's and Women's Hospital Long Beach|