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)

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.

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).

Study Overview

• Status: Completed
• Conditions: Survival Without Progression
• Intervention / Treatment: 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)

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: ARNAUD VERSCHUUR; Phone Number: 04 91 38 84 78; Email: arnaud.verschuur@ap-hm.fr

Study Locations

• France
  • Marseille, France, 13354
    • Assistance Publique Hopitaux de Marseille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: traetment	Drug: celecoxib, Vinblastine, Cyclophosphamide , methotrexate ,

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Anti-tumour efficacy	3 YEARS

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety AND Pharmacodynamic Study	3 YEARS

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille

Publications and helpful links

General Publications

• Verschuur A, Heng-Maillard MA, Dory-Lautrec P, Truillet R, Jouve E, Chastagner P, Leblond P, Aerts I, Honore S, Entz-Werle N, Sirvent N, Gentet JC, Corradini N, Andre N. Metronomic Four-Drug Regimen Has Anti-tumor Activity in Pediatric Low-Grade Glioma; The Results of a Phase II Clinical Trial. Front Pharmacol. 2018 Sep 27;9:00950. doi: 10.3389/fphar.2018.00950. eCollection 2018.
• Andre N, Abed S, Orbach D, Alla CA, Padovani L, Pasquier E, Gentet JC, Verschuur A. Pilot study of a pediatric metronomic 4-drug regimen. Oncotarget. 2011 Dec;2(12):960-5. doi: 10.18632/oncotarget.358.

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2011
• Primary Completion (Actual): September 11, 2015
• Study Completion (Actual): March 9, 2023

Study Registration Dates

• First Submitted: January 6, 2011
• First Submitted That Met QC Criteria: January 27, 2011
• First Posted (Estimate): January 28, 2011

Study Record Updates

• Last Update Posted (Actual): March 13, 2023
• Last Update Submitted That Met QC Criteria: March 9, 2023
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Disease Progression; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Dermatologic Agents; Reproductive Control Agents; Cyclooxygenase 2 Inhibitors; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Cyclophosphamide; Celecoxib; Methotrexate; Vinblastine
• Other Study ID Numbers: 2010-12; 2010-021792-81 (EudraCT Number)