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

• Sponsor: University of South Florida (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00949117
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 9
• Arms: 2
• Duration (Months): 26

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia; Lymphoma; Malnutrition; Myelodysplastic Syndromes; Unspecified Childhood Solid Tumor, Protocol Specific; Weight Changes	Dietary Supplement: Ensure; Dietary Supplement: PediaSure; Drug: cyproheptadine hydrochloride	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: 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
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Nov 1, 2011
• Actual Study Completion Date: Nov 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I- cyproheptadine hydrochloride Patients receive oral cyproheptadine hydrochloride twice daily for up to 24 weeks in the absence of weight loss or unacceptable toxicity.	Drug: cyproheptadine hydrochloride; Given orally; Other Names: cyproheptadine HCl
Experimental: cyproheptadine HCl & PediaSure or Ensure 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.	Dietary Supplement: Ensure; Given orally; Other Names: nutritional supplement drink ; Dietary Supplement: PediaSure; Given orally; Other Names: nutritional supplement drink (pediatric) ; Drug: cyproheptadine hydrochloride; Given orally; Other Names: cyproheptadine HCl

Outcome Measures

Primary Outcome Measures

1. Difference Between Measures of Weight at Baseline and at Week 24 [24 weeks]

   Difference in measure of weight in kilograms of subject at baseline and at week 24 after continuing on study treatment for the entire 24 week period.

Secondary Outcome Measures

1. Body Mass Index as Assessed at Baseline and 24 Weeks [24 weeks]

   Change in Body Mass Index (BMI) in subjects from Baseline visit to 24 week visit.

2. Effect of Cyproheptadine Hydrochloride on Pre-albumin and Body Composition [24 weeks]

3. Quality of Life as Assessed by Peds-FAACT Questionnaire at Baseline and at Weeks 4 and 24 [24 weeks]

4. Change in Weight for Age Z-score From Baseline Through 24 Weeks [Baseline and 24 weeks]

   Change in weight for age Z-score from Baseline through 24 weeks while on study treatment. Weight for age Z-score calculated using the Center for Disease Control and Prevention (CDC) weight-for-age Z score data tables.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• University of South Florida
• National Cancer Institute (NCI)

Investigators

• Study Chair: Marisa Couluris, DO, University of South Florida

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of South Florida
• ClinicalTrials.gov Identifier: NCT00949117
• Other Study ID Numbers: SCUSF 0802; SCUSF-0802; 5U10CA081920-11
• First Posted: Jul 30, 2009
• Last Update Posted: Apr 2, 2014
• Last Verified: Mar 1, 2014

• Keywords provided by University of South Florida: malnutrition; weight changes; childhood acute lymphoblastic leukemia in remission; recurrent childhood acute lymphoblastic leukemia; untreated childhood acute lymphoblastic leukemia; childhood acute myeloid leukemia in remission; recurrent childhood acute myeloid leukemia; untreated childhood acute myeloid leukemia; other myeloid malignancies; stage I childhood Hodgkin lymphoma; stage II childhood Hodgkin lymphoma; stage III childhood Hodgkin lymphoma; stage IV childhood Hodgkin lymphoma; recurrent/refractory childhood Hodgkin lymphoma; recurrent childhood anaplastic large cell lymphoma; stage I childhood anaplastic large cell lymphoma; stage II childhood anaplastic large cell lymphoma; stage III childhood anaplastic large cell lymphoma; stage IV childhood anaplastic large cell lymphoma; recurrent childhood grade III lymphomatoid granulomatosis; childhood diffuse large cell lymphoma; childhood immunoblastic large cell lymphoma; recurrent childhood large cell lymphoma; stage I childhood large cell lymphoma; stage II childhood large cell lymphoma; stage III childhood large cell lymphoma; stage IV childhood large cell lymphoma; recurrent childhood lymphoblastic lymphoma; stage I childhood lymphoblastic lymphoma; stage II childhood lymphoblastic lymphoma; stage III childhood lymphoblastic lymphoma; stage IV childhood lymphoblastic lymphoma; childhood nasal type extranodal NK/T-cell lymphoma; childhood Burkitt lymphoma; recurrent childhood small noncleaved cell lymphoma; stage I childhood small noncleaved cell lymphoma; stage II childhood small noncleaved cell lymphoma; stage III childhood small noncleaved cell lymphoma; stage IV childhood small noncleaved cell lymphoma; childhood myelodysplastic syndromes; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; unspecified childhood solid tumor, protocol specific
• Additional relevant MeSH terms: Lymphoma; Leukemia; Preleukemia; Myelodysplastic Syndromes; Malnutrition; Syndrome; Body Weight; Weight Loss; Body Weight Changes; Cyproheptadine

Study Results

Participant Flow

Arm/Group Title	Arm I- Cyproheptadine Hydrochloride	Arm II Cyproheptadine HCl and PediaSure or Ensure
Arm/Group Description	Patients receive oral cyproheptadine hydrochloride twice daily for up to 24 weeks in the absence of weight loss or unacceptable toxicity.	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.
Period Title: Overall Study
STARTED	4	5
COMPLETED	1	0
NOT COMPLETED	3	5

Baseline Characteristics

Arm/Group Title	Arm I- Cyproheptadine Hydrochloride	Arm II Cyproheptadine HCl and PediaSure or Ensure	Total
Arm/Group Description	Patients receive oral cyproheptadine hydrochloride twice daily for up to 24 weeks in the absence of weight loss or unacceptable toxicity.	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.	Total of all reporting groups
Overall Participants	4	5	9
Age (Count of Participants)
<=18 years	4 100%	5 100%	9 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.1 (5.5)	13.3 (5.1)	11.4 (5.1)
Sex: Female, Male (Count of Participants)
Female	2 50%	0 0%	2 22.2%
Male	2 50%	5 100%	7 77.8%
Region of Enrollment (participants) [Number]
United States	4 100%	5 100%	9 100%

Outcome Measures

1. Primary Outcome

Title	Difference Between Measures of Weight at Baseline and at Week 24
Description	Difference in measure of weight in kilograms of subject at baseline and at week 24 after continuing on study treatment for the entire 24 week period.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I- Cyproheptadine Hydrochloride	Arm II Cyproheptadine HCl and PediaSure or Ensure
Arm/Group Description	Patients receive oral cyproheptadine hydrochloride twice daily for up to 24 weeks in the absence of weight loss or unacceptable toxicity.	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.
Measure Participants	1	0
Mean (Standard Deviation) [kilograms]	4.3

2. Secondary Outcome

Title	Body Mass Index as Assessed at Baseline and 24 Weeks
Description	Change in Body Mass Index (BMI) in subjects from Baseline visit to 24 week visit.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I- Cyproheptadine Hydrochloride	Arm II Cyproheptadine HCl and PediaSure or Ensure
Arm/Group Description	Patients receive oral cyproheptadine hydrochloride twice daily for up to 24 weeks in the absence of weight loss or unacceptable toxicity.	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.
Measure Participants	1	0
Mean (Standard Deviation) [kg/m^2]	1.9

3. Secondary Outcome

Title	Effect of Cyproheptadine Hydrochloride on Pre-albumin and Body Composition
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Outcome not assessed as the one subject that completed the protocol did not have the prealbumin lab drawn at the 24 week visit and body composition tests assessed.

Arm/Group Title	Arm I- Cyproheptadine Hydrochloride	Arm II Cyproheptadine HCl and PediaSure or Ensure
Arm/Group Description	Patients receive oral cyproheptadine hydrochloride twice daily for up to 24 weeks in the absence of weight loss or unacceptable toxicity.	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.
Measure Participants	0	0

4. Secondary Outcome

Title	Quality of Life as Assessed by Peds-FAACT Questionnaire at Baseline and at Weeks 4 and 24
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Outcome not assessed as the one subject that completed the protocol was too young to complete the PedsFAACT quality of life assessment.

Arm/Group Title	Arm I- Cyproheptadine Hydrochloride	Arm II Cyproheptadine HCl and PediaSure or Ensure
Arm/Group Description	Patients receive oral cyproheptadine hydrochloride twice daily for up to 24 weeks in the absence of weight loss or unacceptable toxicity.	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.
Measure Participants	0	0

5. Secondary Outcome

Title	Change in Weight for Age Z-score From Baseline Through 24 Weeks
Description	Change in weight for age Z-score from Baseline through 24 weeks while on study treatment. Weight for age Z-score calculated using the Center for Disease Control and Prevention (CDC) weight-for-age Z score data tables.
Time Frame	Baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I- Cyproheptadine Hydrochloride	Cyproheptadine HCl & PediaSure or Ensure
Arm/Group Description	Patients receive oral cyproheptadine hydrochloride twice daily for up to 24 weeks in the absence of weight loss or unacceptable toxicity. cyproheptadine hydrochloride: Given orally	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. Ensure: Given orally PediaSure: Given orally cyproheptadine hydrochloride: Given orally
Measure Participants	1	0
Mean (Standard Deviation) [z score]	1.47 (0)

Adverse Events

Time Frame	24 weeks
Adverse Event Reporting Description	Subjects and their parents reported any adverse symptoms or events via daily study medication logs. Site personnel reviewed logs at in-person visits at weeks 4, 8, 12, 16, 20 and 24 and assessed subject for any adverse events. All Adverse events and Serious Adverse events reviewed by independent DSMB.
Arm/Group Title	Arm I- Cyproheptadine Hydrochloride		Arm II Cyproheptadine HCl and PediaSure or Ensure
Arm/Group Description	Patients receive oral cyproheptadine hydrochloride twice daily for up to 24 weeks in the absence of weight loss or unacceptable toxicity.		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.
All Cause Mortality
	Arm I- Cyproheptadine Hydrochloride		Arm II Cyproheptadine HCl and PediaSure or Ensure
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I- Cyproheptadine Hydrochloride		Arm II Cyproheptadine HCl and PediaSure or Ensure
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Arm I- Cyproheptadine Hydrochloride		Arm II Cyproheptadine HCl and PediaSure or Ensure
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		2/5 (40%)
Gastrointestinal disorders
flatulence	0/4 (0%)	0	1/5 (20%)	1
General disorders
somnolence	1/4 (25%)	1	0/5 (0%)	0
relapse of cancer	0/4 (0%)	0	1/5 (20%)	1
Skin and subcutaneous tissue disorders
rash	0/4 (0%)	0	1/5 (20%)	1

Limitations/Caveats

Study closed early due to slow accrual and lack of feasibility Only 1 subject completed protocol and considered in the outcome measures. Subject too young to complete PedsFAACT & did not have prealbumin drawn at 24 week visit so outcomes not assessed

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.