Low Dose Chemotherapy Versus Best Supportive Care in Progressive Pediatric Malignancies

All India Institute Of Medical Science (AIIMS)

Status and phase: Completed; Phase 3

Conditions: Malignant Childhood Neoplasm

Treatments: Drug: Low dose chemotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT01858571

IEC/NP-63/2013

Details and patient eligibility

About

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.

Full 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%.

Enrollment: 108 patients

Sex: All

Ages: 5 to 18 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

108 participants in 2 patient groups, including a placebo group

Low dose chemotherapy

Experimental group

Description:

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

Treatment:

Drug: Low dose chemotherapy

Best supportive care

Placebo Comparator group

Description:

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

Treatment:

Drug: Low dose chemotherapy