Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Inflammatory Agents

Analgesics

Thalidomide

Etoposide

Cyclophosphamide

Etoposide phosphate

Celecoxib

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Enzyme Inhibitors

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

Anti-Bacterial Agents

Angiogenesis Inhibitors

Growth Inhibitors

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

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

Low dose chemotherapy

Sameer Bakhshi, MD

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.

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%.

Low Dose Chemotherapy Versus Best Supportive Care in Progressive Pediatric Malignancies

Low Dose Chemotherapy (Metronomic Therapy) Versus Best Supportive Care in Progressive and/or Refractory Pediatric Malignancies: a Double Blind Placebo Controlled Randomized Study

All India Institute of Medical Sciences, New Delhi

Additional Professor

Antiemetics

Dermatologic Agents

Gastrointestinal Agents

Ondansetron

Serotonin

Serotonin 5-HT3 Receptor Antagonists

Neurotransmitter Agents

Group A will receive the standard dose of ondansetron (0.15 mg/kg) with the first cycle of chemotherapy and the high dose (0.3 mg/kg) with second cycle.

Group B patients will receive the higher dose of ondansetron (0.3 mg/kg) with the first cycle of chemotherapy and the standard dose (0.15 mg/kg) with the second.

There will be two doses investigated in each arm - standard dose (0.15 mg/kg) and high dose (0.3 mg/kg)

Rene Y McNall-Knapp, MD

Matthew Campbell, MD

We will study the effects of ondansetron on measurements of electrical activity in the heart to make sure doses we are using to prevent nausea and vomiting in children receiving chemotherapy are safe.

Children receiving chemotherapy for cancer at the Jimmy Everest Center for Cancer and Blood Disorders in Children also often receive an IV dose of an antiemetic for prophylaxis. The most common antiemetics used are in the family of 5HT3 antagonists, specifically granisetron and ondansetron. Prior to a recent recommendation by the FDA, we have used ondansetron 0.45 mg/kg IV. Based on adult ECG data, the recommended dose of ondansetron has been changed to no greater than 0.15 mg/kg. We have prior studies showing that the bigger dose is better at preventing nausea and vomiting. Therefore we are studying ECG data in patients receiving ondansetron and chemotherapy. Each subject will have two identical cycles of chemotherapy. Prior to the first of the two cycles they will be randomized to receive one of two doses of ondansetron with the first cycle and the other dose with the second cycle. The two doses are the recommended dose of 0.15 mg/kg and a higher dose of 0.3 mg/kg. The dose level the patient receives each cycle will be blinded to the investigator and the subject.

Prior to the first dose of investigational ondansetron, the patient will have an ECG. This ECG will be repeated 30 minutes after the ondansetron is administered and just before chemotherapy administration, and repeated again 30 minutes later. The change in the QTc intervals will be calculated by two independent pediatric cardiologists who are also blinded to the ondansetron dose level received. This process will be repeated with the next course of chemotherapy, with the second dose of ondansetron. Our goal is to see if there is an appreciable difference between the two doses in the QTc interval changes they induce.

Heart Safety Study of Ondansetron in Children Receiving Chemotherapy

The Effects of Ondansetron on Myocardial Repolarization in Children Receiving Chemotherapy

QTc intervals will be estimated by performing ECGs on patients pre-investigational drug administration and post-investigational drug administration. The change in the QTc interval between the two ECGs for each investigational dose is the primary endpoint.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Low Dose Chemotherapy Versus Best Supportive Care in Progressive Pediatric Malignancies	NCT01858571	Malignant Child...	Low dose chemot...	5 Years - 18 Years	All India Institute of Medical Sciences, New Delhi
Heart Safety Study of Ondansetron in Children Receiving Chemotherapy	NCT01896440	Malignant Child...	Ondansetron	6 Months - 18 Years	University of Oklahoma
Heart Safety Study of Ondansetron in Children Receiving Chemotherapy	NCT01896440	Malignant Child...	Ondansetron	6 Months - 18 Years	University of Oklahoma

Spots Global Cancer Trial Database for malignant childhood neoplasm