Low Dose Chemotherapy Versus Best Supportive Care in Progressive Pediatric Malignancies
Condition: Malignant Childhood Neoplasm
MeSH terms: Neoplasms
Study type: Interventional
Phase: Phase 3

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.
    

Detailed 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%.
    

Intervention name(s): Low dose chemotherapy
Intervention type(s): Drug
Intervention description(s): 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
Other intervention name(s): •Thalidomide •Celecoxib •Etoposide •Cyclophosphamide
Intervention MeSH terms: Thalidomide; Celecoxib; Cyclophosphamide; Etoposide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: Childhood Cancer