A Clinical Trial Using Metronomic Oral Low-dose Cyclophosphamide Alternating With Low-dose Oral Methotrexate With Continuous Celecoxib and Weekly Vinblastine in Children and Adolescents With Relapsed or Progressing solid Tumours. (SFCE METRO 01)

Sponsor: Assistance Publique Hopitaux De Marseille

Purpose
To establish the anti-tumour effect of this metronomic combination regimen defined by progression-free survival (PFS) after two cycles of treatment (4 months) and 12 months of treatment, as well as response rate after any number of cycles of treatment ("best response").

To define the safety profile of the combination. To characterize pharmacodynamics of the drug combination with the use of angiogenic markers (CEP, CEC, microparticles).

Drug: celecoxib, Vinblastine, Cyclophosphamide , methotrexate ,
Phase II

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Clinical Trial Using Metronomic Oral Low-dose Cyclophosphamide Alternating With Low-dose Oral Methotrexate With Continuous Celecoxib and Weekly Vinblastine in Children and Adolescents With Relapsed or Progressing Solid Tumours.

Primary Outcome Measures:
Anti-tumour efficacy [ Time Frame: 3 YEARS ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
Safety AND Pharmacodynamic Study [ Time Frame: 3 YEARS ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 90
Study Start Date: November 2010
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
traetment: Experimental
Intervention: Drug: celecoxib, Vinblastine, Cyclophosphamide , methotrexate ,
Drug: celecoxib, Vinblastine, Cyclophosphamide , methotrexate ,

Detailed Description:
Multi-center, combination phase II study, open-label, non-comparative, non-randomized.

All progressive or recurrent solid tumours will be included in the Phase II study, provided there are no curative options anymore.

Total expected number of patients (minimum maximum): 54 to 90 (2-stage design)

Eligibility

Ages Eligible for Study: 4 Years to 21 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
Criteria
Inclusion Criteria:

Patients must have a histologically or cytologically confirmed malignant solid tumour.
Progression or recurrence of the tumour radiologically established or confirmed within the 4 weeks prior to inclusion.
Disease must be considered refractory to any line of conventional therapy or for which no effective conventional treatment exists.
Age: ≥4 to 21 years of age at study entry
Life expectancy: at least 8 weeks
ECOG Performance status ≤ 1 or Lansky-Play Scale ≥ 70%
Written informed consent of parent/guardian and patient assent
Wash out of 4 weeks in case of prior chemotherapy, 6 weeks if treatment included nitrosoureas, 2 weeks in case of vincristine alone; 6 weeks in case of prior radiotherapy (except palliative radiotherapy on non measurable lesions).
Patients must have recovered from the acute toxic effects of all prior therapy before enrolment into the study
Able to comply with scheduled follow-up and with management of toxicity
All patients with reproductive potential must practice an effective method of birth control while on study.
Female patients aged > 12 years must have a negative pregnancy test within 7 days before study treatment.
Capable of swallowing oral medication
Exclusion Criteria:

Pregnant and breast feeding women.
Uncontrolled intercurrent illness or active infection
Inability to swallow oral medication.
Patients on anticonvulsants will be allowed on study
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01285817

Locations
France
Assistance Publique Hopitaux de Marseille, Marseille, France, 13354
Contact: arnaud.verschuur@ap-hm.fr
Sponsors and Collaborators
Assistance Publique Hopitaux De Marseille
Study Director: BERNARD BELAIGUES Assistance Publique hôpitaux de Marseille