Low Dose Chemotherapy Versus Best Supportive Care in Progressive Pediatric Malignancies

NCT01858571 | Completed Phase 3 DMC

• 1 other identifier: IEC/NP-63/2013
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Malignant Childhood Neoplasm

Keywords

Childhood Cancer

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Up to 2 years

Secondary Outcomes (1)

• Overall Survival

  Up to 2 years

Other Outcomes (2)

• Quality of life

  Up to 2 years

• Bio marker of angiogenesis (VEGF)

  Up to 2 years

Study Arms (2)

Low dose chemotherapy

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

Drug: Low dose chemotherapy

Best supportive care

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

Drug: Low dose chemotherapy

Interventions

Low dose chemotherapy DRUG

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

Also known as: •Thalidomide •Celecoxib •Etoposide •Cyclophosphamide

Best supportive care; Low dose chemotherapy

Eligibility Criteria

• Age: 5 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Refractory/Progressive non hematopoietic extracranial solid tumors following treatment with at least 2 lines of chemotherapy.
• ECOG performance status (\<=3)(at least patients ambulating with crutches or on wheel chair)
• Age: 5-18 years
• Recovered from all acute toxic effects of earlier therapy
• Absolute neutrophil count \> 1X 109/L
• Absolute platelet count \> 75 x 109/L
• Normal renal functions
• 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.

You may not qualify if:

• Uncontrolled concurrent illness or active infection
• Positive serology for human immunodeficiency.
• Unable to swallow oral medication
• Pregnant and breast-feeding

Sponsors & Collaborators

• All India Institute of Medical Sciences: lead

Study Sites (1)

All India Institute of Medical Sciences

New Delhi, National Capital Territory of Delhi, 110029, India

Location

Related Publications (2)

• Pramanik R, Agarwala S, Sreenivas V, Dhawan D, Bakhshi S. Quality of life in paediatric solid tumours: a randomised study of metronomic chemotherapy versus placebo. BMJ Support Palliat Care. 2023 Jun;13(2):234-237. doi: 10.1136/bmjspcare-2020-002731. Epub 2021 Jan 19.

  PMID: 33468507 DERIVED

• Pramanik R, Agarwala S, Gupta YK, Thulkar S, Vishnubhatla S, Batra A, Dhawan D, Bakhshi S. Metronomic Chemotherapy vs Best Supportive Care in Progressive Pediatric Solid Malignant Tumors: A Randomized Clinical Trial. JAMA Oncol. 2017 Sep 1;3(9):1222-1227. doi: 10.1001/jamaoncol.2017.0324.

  PMID: 28384657 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

Drug Therapy

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Sameer Bakhshi, MD

  All India Institute of Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Additional Professor

Study Record Dates

• First Submitted: May 17, 2013
• First Posted: May 21, 2013
• Study Start: October 1, 2013
• Primary Completion: July 1, 2016
• Study Completion: January 1, 2017
• Last Updated: January 25, 2017

Record last verified: 2017-01

Locations

IN (1)