Overview

This trial is active, not recruiting.

Condition malignant childhood neoplasm
Treatment low dose chemotherapy
Phase phase 3
Sponsor All India Institute of Medical Sciences, New Delhi
Start date October 2013
End date July 2016
Trial size 108 participants
Trial identifier NCT01858571, IEC/NP-63/2013

Summary

Many of the pediatric malignancies are not curable on progression on front line or 2nd line chemotherapy. Further therapy with conventional drugs imposes many side effects and decreases the QOL. The usual therapy offered to such patients is best supportive care.

Metronomic chemotherapy can induce tumor stabilization or tumor responses in patients with cancer that are refractory or have relapsed after conventional chemotherapy. Whether metronomic therapy is better than best supportive care is not known. In order to do so, a study is required which may compare metronomic therapy with a placebo therapy on PFS and QOL in relapsed refractory cases of pediatric solid tumors who have failed at least two lines of chemotherapy.

HYPOTHESIS

The investigators hypothesize that metronomic chemotherapy in progressive pediatric malignancy will improve PFS and QOL. If validated, then this form for therapy will be an option for both the patients and the clinicians, who are left with just an option of best supportive care in such situations of progressive pediatric cancers despite multiple lines of chemotherapy.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver)
Primary purpose treatment
Arm
(Experimental)
Alternating cycles of Cycle A and B (Each cycle includes 3 weeks of drug administration) with each drug rounded off to the nearest tablet/capsule size. Cycle A Daily oral Thalidomide (at 3mg/kg) Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg) Daily oral Etoposide (50 mg/m2/d) Cycle B Daily oral Thalidomide (at 3mg/kg) Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg) Daily oral Cyclophosphamide (2.5 mg/kg/d to a maximum of 100 mg/d) every 21 days
low dose chemotherapy •Thalidomide •Celecoxib •Etoposide •Cyclophosphamide
Metronomic chemotherapy schedule : Alternating cycles of Cycle A and B (Each cycle includes 3 weeks of drug administration) with each drug rounded off to the nearest tablet/capsule size. Cycle A Daily oral Thalidomide (at 3mg/kg) Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg) Daily oral Etoposide (50 mg/m2/d) Cycle B Daily oral Thalidomide (at 3mg/kg) Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg) Daily oral Cyclophosphamide (2.5 mg/kg/d to a maximum of 100 mg/d) every 21 days
(Placebo Comparator)
Placebo: Alternating cycles of Cycle A and B (Each cycle includes 3 weeks of drug administration) Capsules of same size and color as used in metronomic therapy Best supportive care Management of pain as per WHO standard for pain management
low dose chemotherapy •Thalidomide •Celecoxib •Etoposide •Cyclophosphamide
Metronomic chemotherapy schedule : Alternating cycles of Cycle A and B (Each cycle includes 3 weeks of drug administration) with each drug rounded off to the nearest tablet/capsule size. Cycle A Daily oral Thalidomide (at 3mg/kg) Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg) Daily oral Etoposide (50 mg/m2/d) Cycle B Daily oral Thalidomide (at 3mg/kg) Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg) Daily oral Cyclophosphamide (2.5 mg/kg/d to a maximum of 100 mg/d) every 21 days

Primary Outcomes

Measure
Progression free survival
time frame: Up to 2 years

Secondary Outcomes

Measure
Overall Survival
time frame: Up to 2 years

Eligibility Criteria

Male or female participants from 5 years up to 18 years old.

Inclusion Criteria: 1. Refractory/Progressive non hematopoietic extracranial solid tumors following treatment with at least 2 lines of chemotherapy. 2. ECOG performance status (<=3)(at least patients ambulating with crutches or on wheel chair) 3. Age: 5-18 years 4. Recovered from all acute toxic effects of earlier therapy 5. Absolute neutrophil count > 1X 109/L 6. Absolute platelet count > 75 x 109/L 7. Normal renal functions 8. Serum bilirubin <1.5 times the upper limit of normal, and the serum aspartate aminotransferase and alanine aminotransferase < 5 times the upper limit of normal. Exclusion Criteria: 1. Uncontrolled concurrent illness or active infection 2. Positive serology for human immunodeficiency. 3. Unable to swallow oral medication 4. Pregnant and breast-feeding

Additional Information

Official title Low Dose Chemotherapy (Metronomic Therapy) Versus Best Supportive Care in Progressive and/or Refractory Pediatric Malignancies: a Double Blind Placebo Controlled Randomized Study
Principal investigator Sameer Bakhshi, MD
Description Many of the pediatric malignancies are not curable on progression on front line or 2nd line chemotherapy. Further therapy with conventional drugs imposes many side effects and decreases the QOL. The usual therapy offered to such patients is best supportive care. Metronomic chemotherapy can induce tumor stabilization or tumor responses in patients with cancer that are refractory or have relapsed after conventional chemotherapy. Whether metronomic therapy is better than best supportive care is not known. In order to do so, a study is required which may compare metronomic therapy with a placebo therapy on PFS and QOL in relapsed refractory cases of pediatric solid tumors who have failed at least two lines of chemotherapy. It will be double blind randomized study. One group will receive metronomic therapy along with best supportive care and other will receive placebo and best supportive care. The treatment will be continued till progression is documented. Metronomic chemotherapy schedule : Alternating cycles of Cycle A and B (Each cycle includes 3 weeks of drug administration) with each drug rounded off to the nearest tablet/capsule size. Cycle A - Daily oral Thalidomide (at 3mg/kg) - Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg) - Daily oral Etoposide (50 mg/m2/d) Cycle B - Daily oral Thalidomide (at 3mg/kg) - Daily oral Celecoxib (100 mg BID for patients < 20 kg, 200 mg BID for patients 20-50 kg, and 400 mg BID for patients > 50 kg) - Daily oral Cyclophosphamide (2.5 mg/kg/d to a maximum of 100 mg/d) every 21 days Placebo: Alternating cycles of Cycle A and B (Each cycle includes 3 weeks of drug administration) - Capsules of same size and color as used in metronomic therapy Best supportive care - Management of pain as per WHO standard for pain management The dose of medications in capsules have to be rounded off to the nearest capsule size. Instead of rounding off on the daily dose, the total dose over the week would be calculated and rounded off and divided over 5-6 days in a week. This is being done so as to prevent any extra dosing. If any grade 3-4 toxicity occurs in the first course, then the dose for chemotherapy would be reduced in the subsequent course by 20%.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by All India Institute of Medical Sciences, New Delhi.