Cyproheptadine in Preventing Weight Loss in Children Receiving Chemotherapy for Cancer

• Sponsor: University of South Florida (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01132547
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 22
• Locations: 14
• Arms: 2
• Duration (Months): 43
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Cyproheptadine hydrochloride may prevent weight loss caused by cancer or cancer treatment. It is not yet known whether cyproheptadine is more effective than a placebo in preventing weight loss in young patients receiving chemotherapy for cancer.

PURPOSE: This randomized phase III trial is studying cyproheptadine hydrochloride to see how well it works in preventing weight loss in young patients receiving chemotherapy for cancer.

Condition or Disease	Intervention/Treatment	Phase
Cancer	Drug: cyproheptadine hydrochloride; Other: placebo	Phase 3

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Supportive Care
• Official Title: Prevention of Cancer/Treatment-Related Weight Loss in Children at High Nutritional Risk
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I cyproheptadine hydrochloride Patients receive oral cyproheptadine hydrochloride twice daily for 8 weeks.	Drug: cyproheptadine hydrochloride; Given orally; Other Names: cyproheptadine HCl
Placebo Comparator: Arm II placebo Patients receive an oral placebo twice daily for 8 weeks.	Other: placebo; Given orally

Outcome Measures

Primary Outcome Measures

1. Participant With Weight Loss ≥ 5% at the 8- Week Assessment When Compared to Baseline [8 weeks]

2. Severity of Weight Loss [Baseline and 8 weeks]

   Change from Baseline in Weight Z score

Secondary Outcome Measures

1. Pattern of Weight in the Study Population [Baseline and 8 weeks]

   Change from Baseline in Weight

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Miller Children's Hospital	Long Beach	California	United States	90806
2	Connecticut Children's Medical Center	Hartford	Connecticut	United States	06106
3	A.I. duPont Hospital for Children	Wilmington	Delaware	United States	19803
4	Children's National Medical Center	Washington	District of Columbia	United States	20010
5	Children's Hospital of Southwest Florida at Lee Memorial	Fort Myers	Florida	United States	33908
6	Nemours Children's Clinic - Jacksonville	Jacksonville	Florida	United States	32207-8482
7	Arnold Palmer Hospital for Children	Orlando	Florida	United States	32806
8	Nemours Children's Clinic - Orlando	Orlando	Florida	United States	32806
9	Nemours Children's Hospital Pensacola	Pensacola	Florida	United States	32504
10	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
11	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
12	Columbia University Medical Center	New York	New York	United States	10032
13	CHRISTUS Santa Rosa Children's Hospital	San Antonio	Texas	United States	78207
14	Children's Hospital of The King's Daughters	Norfolk	Virginia	United States	23507

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Jeffrey P. Krischer, PhD, University of South Florida

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of South Florida
• ClinicalTrials.gov Identifier: NCT01132547
• Other Study ID Numbers: SCUSF 0703; SCUSF-0703; 5U10CA081920-11
• First Posted: May 28, 2010
• Last Update Posted: Jul 2, 2015
• Last Verified: Jun 1, 2015

• Keywords provided by University of South Florida: cachexia; weight changes; nausea and vomiting; alveolar childhood rhabdomyosarcoma; anaplastic osteosarcoma; childhood alveolar soft-part sarcoma; childhood angiosarcoma; childhood epithelioid sarcoma; childhood fibrosarcoma; childhood gliosarcoma; childhood leiomyosarcoma; childhood liposarcoma; childhood neurofibrosarcoma; childhood synovial sarcoma; chondrosarcoma; chondrosarcomatous osteosarcoma; clear cell sarcoma of the kidney; embryonal childhood rhabdomyosarcoma; embryonal-botryoid childhood rhabdomyosarcoma; endometrial stromal sarcoma; extraosseous Ewing sarcoma; peripheral primitive neuroectodermal tumor; fibrosarcomatous osteosarcoma; localized Ewing sarcoma; localized osteosarcoma; mast cell sarcoma; metastatic childhood soft tissue sarcoma; metastatic Ewing sarcoma; metastatic osteosarcoma; mixed childhood rhabdomyosarcoma; mixed osteosarcoma; nonmetastatic childhood soft tissue sarcoma; osteoblastic osteosarcoma; ovarian carcinosarcoma; ovarian sarcoma; pleomorphic childhood rhabdomyosarcoma; previously treated childhood rhabdomyosarcoma; previously untreated childhood rhabdomyosarcoma; recurrent adult soft tissue sarcoma; recurrent childhood gliosarcoma; recurrent childhood rhabdomyosarcoma; recurrent childhood soft tissue sarcoma; recurrent Ewing sarcoma; recurrent osteosarcoma; recurrent uterine sarcoma; small intestine leiomyosarcoma; stage I uterine sarcoma; stage II uterine sarcoma; stage III uterine sarcoma; stage IV uterine sarcoma; telangiectatic osteosarcoma; untreated childhood gliosarcoma; uterine carcinosarcoma; uterine leiomyosarcoma; localized resectable neuroblastoma; localized unresectable neuroblastoma; recurrent neuroblastoma; regional neuroblastoma; stage 4S neuroblastoma; recurrent Wilms tumor; childhood kidney tumors; stage III Wilms tumor; stage IV Wilms tumor; childhood hepatoblastoma; childhood extracranial germ cell tumor; childhood extragonadal germ cell tumor; childhood gonadal germ cell tumor; childhood malignant ovarian germ cell tumor; childhood malignant testicular germ cell tumor; recurrent childhood malignant germ cell tumor; recurrent extragonadal germ cell tumor; recurrent extragonadal non-seminomatous germ cell tumor; recurrent malignant testicular germ cell tumor; recurrent ovarian germ cell tumor; stage III extragonadal non-seminomatous germ cell tumor; stage III malignant testicular germ cell tumor; stage IIIA ovarian germ cell tumor; stage IIIB ovarian germ cell tumor; stage IIIC ovarian germ cell tumor; stage IV extragonadal non-seminomatous germ cell tumor; stage IV ovarian germ cell tumor; recurrent childhood medulloblastoma; untreated childhood medulloblastoma; childhood ependymoblastoma; childhood infratentorial ependymoma; newly diagnosed childhood ependymoma; recurrent childhood ependymoma; recurrent childhood subependymal giant cell astrocytoma; untreated childhood subependymal giant cell astrocytoma; peripheral primitive neuroectodermal tumor of the kidney; childhood supratentorial primitive neuroectodermal tumor; recurrent childhood brain stem glioma; recurrent childhood brain tumor; untreated childhood brain stem glioma; recurrent childhood anaplastic astrocytoma; recurrent childhood anaplastic oligoastrocytoma; recurrent childhood anaplastic oligodendroglioma; 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; untreated childhood anaplastic astrocytoma; untreated childhood anaplastic oligoastrocytoma; untreated childhood anaplastic oligodendroglioma; childhood high-grade cerebellar astrocytoma; childhood low-grade cerebellar astrocytoma; recurrent childhood astrocytoma; other tumor of glial origin; recurrent childhood cerebellar astrocytoma; recurrent childhood cerebral astrocytoma; recurrent childhood diffuse astrocytoma; recurrent childhood fibrillary astrocytoma; recurrent childhood gemistocytic astrocytoma; recurrent childhood oligoastrocytoma; recurrent childhood pilocytic astrocytoma; recurrent childhood pilomyxoid astrocytoma; recurrent childhood pleomorphic xanthoastrocytoma; recurrent childhood protoplasmic astrocytoma; untreated childhood cerebellar astrocytoma; untreated childhood cerebral astrocytoma; untreated childhood diffuse astrocytoma; untreated childhood fibrillary astrocytoma; untreated childhood gemistocytic astrocytoma; untreated childhood oligoastrocytoma; untreated childhood pilocytic astrocytoma; untreated childhood pilomyxoid astrocytoma; untreated childhood pleomorphic xanthoastrocytoma; untreated childhood protoplasmic astrocytoma; recurrent childhood gliomatosis cerebri; recurrent childhood oligodendroglioma; recurrent childhood visual pathway; hypothalamic glioma; recurrent childhood visual pathway glioma; untreated childhood gliomatosis cerebri; untreated childhood oligodendroglioma; untreated childhood visual pathway; untreated childhood visual pathway glioma; recurrent childhood giant cell glioblastoma; recurrent childhood glioblastoma; untreated childhood giant cell glioblastoma; untreated childhood glioblastoma; childhood choroid plexus tumor; childhood grade I meningioma; childhood grade II meningioma; childhood grade III meningioma; minimally differentiated myeloid leukemia (M0); myeloblastic leukemia with maturation (M2); myeloblastic leukemia without maturation (M1); childhood acute myelomonocytic leukemia (M4); childhood acute promyelocytic leukemia (M3); recurrent childhood acute myeloid leukemia; untreated childhood acute myeloid leukemia; other myeloid malignancies; childhood acute monoblastic leukemia (M5a); childhood acute monocytic leukemia (M5b); childhood acute erythroleukemia (M6); childhood acute megakaryocytic leukemia (M7); unspecified childhood solid tumor
• Additional relevant MeSH terms: Weight Loss; Cyproheptadine

Study Results

Participant Flow

Arm/Group Title	Arm I Cyproheptadine Hydrochloride	Arm II Placebo
Arm/Group Description	Patients receive oral cyproheptadine hydrochloride twice daily for 8 weeks. cyproheptadine hydrochloride: Given orally	Patients receive an oral placebo twice daily for 8 weeks. placebo: Given orally
Period Title: Overall Study
STARTED	9	13
COMPLETED	5	12
NOT COMPLETED	4	1

Baseline Characteristics

Arm/Group Title	Arm I Cyproheptadine Hydrochloride	Arm II Placebo	Total
Arm/Group Description	Patients receive oral cyproheptadine hydrochloride twice daily for 8 weeks. cyproheptadine hydrochloride: Given orally	Patients receive an oral placebo twice daily for 8 weeks. placebo: Given orally	Total of all reporting groups
Overall Participants	9	13	22
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10.2 (5.7)	12.0 (4.7)	11.2 (5.1)
Sex: Female, Male (Count of Participants)
Female	3 33.3%	10 76.9%	13 59.1%
Male	6 66.7%	3 23.1%	9 40.9%
Region of Enrollment (participants) [Number]
United States	9 100%	13 100%	22 100%

Outcome Measures

1. Primary Outcome

Title	Participant With Weight Loss ≥ 5% at the 8- Week Assessment When Compared to Baseline
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

LOCF

Arm/Group Title	Arm I Cyproheptadine Hydrochloride	Arm II Placebo
Arm/Group Description	Patients receive oral cyproheptadine hydrochloride twice daily for 8 weeks. cyproheptadine hydrochloride: Given orally	Patients receive an oral placebo twice daily for 8 weeks. placebo: Given orally
Measure Participants	9	13
Number [participants]	0 0%	2 15.4%

2. Primary Outcome

Title	Severity of Weight Loss
Description	Change from Baseline in Weight Z score
Time Frame	Baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

Completers =

Arm/Group Title	Arm I Cyproheptadine Hydrochloride	Arm II Placebo
Arm/Group Description	Patients receive oral cyproheptadine hydrochloride twice daily for 8 weeks. cyproheptadine hydrochloride: Given orally	Patients receive an oral placebo twice daily for 8 weeks. placebo: Given orally
Measure Participants	5	12
Mean (Standard Deviation) [Z score]	0.12 (1.15)	-0.02 (0.30)

3. Secondary Outcome

Title	Pattern of Weight in the Study Population
Description	Change from Baseline in Weight
Time Frame	Baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

Completers

Arm/Group Title	Arm I Cyproheptadine Hydrochloride	Arm II Placebo
Arm/Group Description	Patients receive oral cyproheptadine hydrochloride twice daily for 8 weeks. cyproheptadine hydrochloride: Given orally	Patients receive an oral placebo twice daily for 8 weeks. placebo: Given orally
Measure Participants	5	12
Mean (Standard Deviation) [Kilograms]	0.18 (0.79)	-0.32 (3.13)

Adverse Events

Arm/Group Title	Arm I Cyproheptadine Hydrochloride		Arm II Placebo
Arm/Group Description	Patients receive oral cyproheptadine hydrochloride twice daily for 8 weeks. cyproheptadine hydrochloride: Given orally		Patients receive an oral placebo twice daily for 8 weeks. placebo: Given orally
All Cause Mortality
	Arm I Cyproheptadine Hydrochloride		Arm II Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I Cyproheptadine Hydrochloride		Arm II Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/9 (33.3%)		0/13 (0%)
Blood and lymphatic system disorders
Febrile Neutropenia	2/9 (22.2%)	3	0/13 (0%)	0
Investigations
Platelet count decrease	2/9 (22.2%)	2	0/13 (0%)	0
Neutrophil count decrease	1/9 (11.1%)	2	0/13 (0%)	0
Nervous system disorders
Intracranial hemorrhage	1/9 (11.1%)	1	0/13 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm I Cyproheptadine Hydrochloride		Arm II Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/9 (44.4%)		4/13 (30.8%)
Blood and lymphatic system disorders
Anemia	2/9 (22.2%)	4	0/13 (0%)	0
Febrile neutropenia	1/9 (11.1%)	1	0/13 (0%)	0
Cardiac disorders
Tachycardia NOS	0/9 (0%)	0	1/13 (7.7%)	1
Gastrointestinal disorders
Abdominal pain	1/9 (11.1%)	1	1/13 (7.7%)	1
Constipation	0/9 (0%)	0	1/13 (7.7%)	1
Mucositis oral	1/9 (11.1%)	1	0/13 (0%)	0
Nausea	0/9 (0%)	0	1/13 (7.7%)	1
General disorders
Fever	2/9 (22.2%)	3	0/13 (0%)	0
Pain	1/9 (11.1%)	1	0/13 (0%)	0
Immune system disorders
Allergic reaction	1/9 (11.1%)	1	0/13 (0%)	0
Musculoskeletal and connective tissue disorders
Pain in extremity	1/9 (11.1%)	1	0/13 (0%)	0
Nervous system disorders
Headache	1/9 (11.1%)	1	1/13 (7.7%)	1
Somnolence	0/9 (0%)	0	1/13 (7.7%)	1
Psychiatric disorders
Insomnia	0/9 (0%)	0	1/13 (7.7%)	1
Skin and subcutaneous tissue disorders
Skin and Subcutaneous tissue disorders other	2/9 (22.2%)	2	1/13 (7.7%)	1
Vascular disorders
Hypertension	1/9 (11.1%)	1	0/13 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.