Cyproheptadine in Preventing Weight Loss in Children Receiving Chemotherapy for Cancer

OBJECTIVES:

Primary

- To determine the effect of cyproheptadine hydrochloride in the prevention of cancer- or
treatment-related weight loss (defined as ≥ 5% reduction in weight from baseline
measurement) in children who are initiating a course of moderately or highly emetic
chemotherapy.

Secondary

- To investigate the effect of cyproheptadine HCl on the change in weight for age scores
after 8 weeks of study drug administration in comparison to placebo.

- Investigate the relationship between the secondary outcome variables (prealbumin,
triceps skin fold, mid-upper arm circumference, and weight loss)from baseline to end of
treatment in each group (treatment and placebo) separately.

OUTLINE: This is a multicenter study. Patients are stratified according to enrolling center
and steroid use with cancer treatment (yes vs no). Study agent can start anytime up to and
including day 28 after the first dose of chemotherapy.

- Arm I: Patients receive oral cyproheptadine hydrochloride twice daily for 8 weeks.

- Arm II: Patients receive an oral placebo twice daily for 8 weeks.

Patients undergo weight and height measurements at baseline and at each follow-up visit in
weeks 4 and 8 to evaluate the effect of cyproheptadine hydrochloride and duration of
response. Patients or parents complete medicine logs at each follow-up visit in weeks 4 and
8 to evaluate drug compliance and tolerance. Patients also undergo measures of nutrition;
and measures of body composition, lean body mass, and fat percentage using standardized
equipment and procedures for measuring triceps skin fold and mid-arm muscle circumference at
baseline and at the end of the study.

Patients undergo blood sample collection at baseline and at the end of the study for
biomarker studies. Samples are analyzed for pre-albumin levels.

INCLUSION CRITERIA:

- ≥ 2 years and ≤ 21 years of age at the time of study entry

- Scheduled to receive chemotherapy for:

- Newly diagnosed:

- Non-rhabdo soft tissue sarcomas, scheduled to receive chemotherapy, as well as
intermediate or high-risk rhabdomyosarcoma, any stage osteosarcoma and any stage
Ewing's sarcoma

- Intermediate or high-risk neuroblastoma

- Wilms' tumor (Stage III/IV)

- Hepatoblastoma (Stage III/IV)

- Germ cell tumors (Stage III/IV)

- Brain tumors, including medulloblastoma, PNET and ependymomas

- AML

- Relapsed/recurrent disease (any patient)

- Able to register and randomize within 28 days of starting chemotherapy (registration
/randomization and start of study agent may occur at anytime up to and including Day
28 after the initiation of chemotherapy)

EXCLUSION CRITERIA:

- ≥ 29 days after starting chemotherapy

- Documented history of unintended weight loss ≥ 5% presumed secondary to cancer within
3 months of study entry

- Currently taking cyproheptadine HCl (or have taken cyproheptadine HCl within 3 weeks
of study registration)

- History of anorexia nervosa or bulimia

- Taking other appetite-stimulating medications, i.e. dronabinol (Marinol) during the
past three weeks.

- Initiation of other appetite enhancing agents, including steroids prescribed for the
intent of weight gain, i.e. Megace. Note: Other forms of nutrition therapies, e.g.
appetite-stimulating medications, TPN or enteral tube feedings are not allowed during
this study.

- Children receiving steroids for >7 days as part of their cancer treatment regimen are
excluded from participation. However, intermittent steroid use in an antiemetic
regimen is allowed during the study

- Receiving monoamine oxidase (MAO) inhibitors, procarbazine, fluoxetine (Prozac), or
paroxetine (Paxil)

- Diagnosed with glaucoma, cystic fibrosis, inflammatory bowel disease, or GI/GU
obstruction

- Allergy to cyproheptadine HCl

- Females of childbearing age must not be pregnant.

- Female patients who are lactating must agree to stop breast-feeding.