Metronomic Therapy for Pediatric Patients With Solid Tumors at High Risk of Recurrence

Part of paid clinical trials in Long Beach, California.

Sponsor
Miller Children's & Women's Hospital Long Beach
Study ID
NCT02446431
Phase
EARLY_PHASE1
Status
Recruiting
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Conditions

  • Solid Tumor

Eligibility Criteria

Sex
ALL
Age
12 Months - 31 Years
Healthy Volunteers
Not accepted

Interventions

  • Bevacizumab — DRUG
    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.
  • Cyclophosphamide — DRUG
    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.
  • Valproic Acid — DRUG
    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.
  • Temsirolimus — DRUG
    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.

Study Details

Most pediatric patients with solid tumors respond to initial high-dose, intensive therapy and complete treatment in remission. High-risk patients however, frequently have recurrent disease which is then treated with ad hoc regimens or early phase therapies with little benefit to the patient. Metronomic therapy (MC), defined as lower dose continuous drug exposure, has been successfully tested in pediatric leukemias with excellent results in terms of improved outcome, toxicity profiles, and cost. MC has been applied to solid tumors with little success, but has been implemented usually in the relapsed setting at a time of high tumor burden and disease resistance.

Key Dates

Start date
Jul 31, 2014
Status verified
May 2015
Primary completion
Jul 31, 2024
Completion
Jul 31, 2029

Study Design

Enrollment
20 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION

Arms

  • 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). 1. Bevacizumab: IV, 10 mg/kg, Days 1, 8 2. Cyclophosphamide: PO, 25 mg/m2 Days 1-14 (max dose = 50mg/dose) 3. Valproic Acid: PO, 5 mg/kg, three times per day (TID), Days 22-35 4. Temsirolimus: IV, 25 mg/m2, Days 22, 29

Primary Outcome Measure

5 year Event Free Survival [ Time Frame: Up to five years off therapy ]

Central Contacts

Locations (2)

FacilityCityStateZIPSite coordinators
Miller Children's and Women's Hospital Long BeachLong BeachCalifornia90806
Ted Zwerdling, MD
[email protected]
562-933-8600
Devin Murphy, MSW
[email protected]
562-933-8601
Children's Hospital Orange CountyOrangeCalifornia92868
Elyssa Rubin, MD
[email protected]
714-509-4348
Dorian Chan, RN,BSN,CCRC
[email protected]
714-509-7868
Elyssa Rubin, MD (PRINCIPAL_INVESTIGATOR)

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