Cyproheptadine Hydrochloride and Nutritional Supplementation in Treating Young Patients With Weight Loss With Cancer

An Open Label Randomized Phase II Study of an Appetite Stimulant, Cyproheptadine Hydrochloride, With and Without a Nutritional Supplement, in Children With Cancer/Treatment-Related Weight Loss

RATIONALE: Cyproheptadine hydrochloride may help improve appetite and lessen weight loss caused by cancer or cancer treatment. It is not yet known whether cyproheptadine hydrochloride is more effective with or without nutritional supplementation in improving weight and quality of life of young patients with weight loss caused by cancer or cancer treatment.

PURPOSE: This randomized phase II trial is studying cyproheptadine hydrochloride to see how well it works when given together with or without nutritional supplementation in treating young patients with weight loss caused by cancer or cancer treatment.

OBJECTIVES:

Primary

• To compare the efficacy of an appetite stimulant, cyproheptadine hydrochloride, with vs without a nutritional supplement, PediaSure or Ensure, in improving weight and extending the duration of response in pediatric patients with cancer- or cancer treatment-related weight loss.

Secondary

• To compare patterns of body composition and weight change in patients treated with these regimens.
• To compare the change in the relationship between pre-albumin (biomarker of malnutrition) and weight improvement from baseline to the completion of study treatment.
• To compare the change in quality of life as measured by the Pediatric Functional Assessment of Anorexia and Cachexia Therapy (FAACT) questionnaire in patients treated with these regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to participating center and steroid use (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral cyproheptadine hydrochloride twice daily for up to 24 weeks in the absence of weight loss or unacceptable toxicity.
• Arm II: Patients receive oral cyproheptadine hydrochloride twice daily and oral PediaSure (2 to 10 years of age) or Ensure (> 10 years of age) twice daily for up to 24 weeks in the absence of weight loss or unacceptable toxicity.

Patients undergo blood sample collection to assess pre-albumin levels at baseline and at weeks 4 and 24. Patients also undergo assessment of body composition, lean body mass, and percentage of body fat at baseline and at weeks 4 and 24 and assessment of weight and height at baseline and at weeks 4, 8, 12, 16, 20, and 24. Patients also complete a food diary twice a week during study treatment.

Patients 7-17 years of age complete a quality-of-life questionnaire at baseline and at weeks 4 and 24.

INCLUSION CRITERIA:

• ≥ 2 years and < 18 years of age at the time of admission to the study
• Meets one of the following criteria:
• documented history of unintended weight loss > 5% presumed secondary to cancer/treatment-related therapy within three months
• BMI for age less than the 5th percentile
• Diagnosed with cancer of any type
• Concomitant cancer treatment (surgery, chemotherapy, radiotherapy) guidelines:
• Patients who will complete concomitant cancer treatment during this study's 4-week intervention are not eligible
• If patients are receiving concomitant cancer treatment, they should be scheduled to get at least another 4 weeks of treatment in order to reach the primary endpoint
• If patients have already completed cancer treatment, they need to be enrolled within 8 weeks of completing therapy.
• Predicted life expectancy of at least 6 months

EXCLUSION CRITERIA:

• Currently taking any of the study agents (cyproheptadine hydrochloride (CH), PediaSure, or Ensure) or have taken any of the study agents during the past 3 weeks
• History of anorexia nervosa or bulimia
• Initiation of other appetite enhancing agents including steroids prescribed for the intent of weight gain, i.e. Megace, is not allowed during this study
• Children receiving steroids as part of their daily cancer treatment regimen are excluded from participation. However, intermittent steroid use in an antiemetic regimen or in other pulse steroid therapy is allowed during the study.
• Use of other forms of nutrition therapies, e.g. total parenteral nutrition (TPN) or enteral tube feedings within 3 weeks of study entry or during study
• Receiving monoamine oxidase (MAO) inhibitors, procarbazine, fluoxetine (SSRI), or paroxetine (SSRI)
• Taking dronabinol (Marinol) or other appetite-stimulating medications during the past 3 weeks
• Diagnosed with glaucoma, cystic fibrosis, inflammatory bowel disease or GI or genitourinary (GU) obstruction
• Allergy to study agents
• Hypersensitivity to specific milk proteins
• Pregnant or lactating. Females of childbearing potential are required to use effective contraception while on study agent.