Cyproheptadine in Preventing Weight Loss in Children Receiving Chemotherapy for Cancer

Prevention of Cancer/Treatment-Related Weight Loss in Children at High Nutritional Risk

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.

Study Overview

• Status: Terminated
• Conditions: Cancer
• Intervention / Treatment: Other: placebo; Drug: cyproheptadine hydrochloride

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 Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90806
      • Miller Children's Hospital
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Connecticut Children's Medical Center
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • A.I. Dupont Hospital for Children
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Fort Myers, Florida, United States, 33908
      • Children's Hospital of Southwest Florida at Lee Memorial
    • Jacksonville, Florida, United States, 32207-8482
      • Nemours Children's Clinic - Jacksonville
    • Orlando, Florida, United States, 32806
      • Nemours Children's Clinic - Orlando
    • Orlando, Florida, United States, 32806
      • Arnold Palmer Hospital for Children
    • Pensacola, Florida, United States, 32504
      • Nemours Children's Hospital Pensacola
  • Hawaii
    • Honolulu, Hawaii, United States, 96826
      • Kapiolani Medical Center for Women and Children
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Texas
    • San Antonio, Texas, United States, 78207
      • Christus Santa Rosa Children's Hospital
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of The King's Daughters

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participant With Weight Loss ≥ 5% at the 8- Week Assessment When Compared to Baseline		8 weeks
Severity of Weight Loss	Change from Baseline in Weight Z score	Baseline and 8 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of South Florida
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jeffrey P. Krischer, PhD, University of South Florida

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: May 26, 2010
• First Submitted That Met QC Criteria: May 26, 2010
• First Posted (Estimate): May 28, 2010

Study Record Updates

• Last Update Posted (Estimate): July 2, 2015
• Last Update Submitted That Met QC Criteria: June 4, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: stage III malignant testicular germ cell tumor; untreated childhood brain stem glioma; chondrosarcoma; cachexia; childhood supratentorial primitive neuroectodermal tumor; localized osteosarcoma; previously treated childhood rhabdomyosarcoma; recurrent childhood rhabdomyosarcoma; localized unresectable neuroblastoma; recurrent neuroblastoma; stage 4S neuroblastoma; recurrent adult soft tissue sarcoma; small intestine leiomyosarcoma; stage IV uterine sarcoma; recurrent uterine sarcoma; uterine carcinosarcoma; uterine leiomyosarcoma; endometrial stromal sarcoma; ovarian sarcoma; regional neuroblastoma; untreated childhood medulloblastoma; untreated childhood cerebellar astrocytoma; untreated childhood cerebral astrocytoma; childhood infratentorial ependymoma; newly diagnosed childhood ependymoma; stage I uterine sarcoma; stage II uterine sarcoma; stage III uterine sarcoma; recurrent ovarian germ cell tumor; stage IV ovarian germ cell tumor; recurrent childhood acute myeloid leukemia; recurrent malignant testicular germ cell tumor; stage III Wilms tumor; stage IV Wilms tumor; metastatic osteosarcoma; recurrent osteosarcoma; childhood acute erythroleukemia (M6); childhood acute megakaryocytic leukemia (M7); nausea and vomiting; clear cell sarcoma of the kidney; stage IIIA ovarian germ cell tumor; stage IIIB ovarian germ cell tumor; stage IIIC ovarian germ cell tumor; childhood acute promyelocytic leukemia (M3); stage III childhood anaplastic large cell lymphoma; stage IV childhood anaplastic large cell lymphoma; recurrent childhood cerebellar astrocytoma; recurrent childhood cerebral astrocytoma; recurrent childhood ependymoma; recurrent childhood brain tumor; metastatic childhood soft tissue sarcoma; recurrent childhood soft tissue sarcoma; recurrent childhood brain stem glioma; recurrent childhood medulloblastoma; childhood choroid plexus tumor; childhood grade I meningioma; childhood grade II meningioma; childhood grade III meningioma; childhood malignant testicular germ cell tumor; childhood malignant ovarian germ cell tumor; childhood extragonadal germ cell tumor; recurrent childhood malignant germ cell tumor; stage I childhood anaplastic large cell lymphoma; stage II childhood anaplastic large cell lymphoma; alveolar childhood rhabdomyosarcoma; embryonal childhood rhabdomyosarcoma; embryonal-botryoid childhood rhabdomyosarcoma; mixed childhood rhabdomyosarcoma; pleomorphic childhood rhabdomyosarcoma; previously untreated childhood rhabdomyosarcoma; nonmetastatic childhood soft tissue sarcoma; localized resectable neuroblastoma; weight changes; childhood acute myelomonocytic leukemia (M4); childhood acute monoblastic leukemia (M5a); childhood acute monocytic leukemia (M5b); untreated childhood acute myeloid leukemia; other myeloid malignancies; recurrent Wilms tumor; recurrent extragonadal non-seminomatous germ cell tumor; stage III extragonadal non-seminomatous germ cell tumor; stage IV extragonadal non-seminomatous germ cell tumor; recurrent extragonadal germ cell tumor; childhood fibrosarcoma; ovarian carcinosarcoma; untreated childhood visual pathway glioma; recurrent childhood visual pathway glioma; childhood low-grade cerebellar astrocytoma; childhood synovial sarcoma; childhood neurofibrosarcoma; childhood extracranial germ cell tumor; peripheral primitive neuroectodermal tumor of the kidney; childhood ependymoblastoma; childhood high-grade cerebellar astrocytoma; recurrent childhood subependymal giant cell astrocytoma; childhood alveolar soft-part sarcoma; childhood angiosarcoma; childhood epithelioid sarcoma; childhood leiomyosarcoma; childhood liposarcoma; recurrent childhood anaplastic astrocytoma; recurrent childhood anaplastic oligoastrocytoma; recurrent childhood anaplastic oligodendroglioma; recurrent childhood diffuse astrocytoma; recurrent childhood fibrillary astrocytoma; recurrent childhood gemistocytic astrocytoma; recurrent childhood giant cell glioblastoma; recurrent childhood glioblastoma; recurrent childhood gliomatosis cerebri; recurrent childhood gliosarcoma; recurrent childhood oligoastrocytoma; recurrent childhood oligodendroglioma; recurrent childhood pilocytic astrocytoma; recurrent childhood pilomyxoid astrocytoma; recurrent childhood pleomorphic xanthoastrocytoma; recurrent childhood protoplasmic astrocytoma; unspecified childhood solid tumor; hypothalamic glioma; untreated childhood visual pathway; childhood hepatoblastoma; anaplastic osteosarcoma; childhood gliosarcoma; chondrosarcomatous osteosarcoma; extraosseous Ewing sarcoma; peripheral primitive neuroectodermal tumor; fibrosarcomatous osteosarcoma; localized Ewing sarcoma; mast cell sarcoma; metastatic Ewing sarcoma; mixed osteosarcoma; osteoblastic osteosarcoma; recurrent Ewing sarcoma; telangiectatic osteosarcoma; untreated childhood gliosarcoma; childhood kidney tumors; childhood gonadal germ cell tumor; untreated childhood subependymal giant cell astrocytoma; untreated childhood anaplastic astrocytoma; untreated childhood anaplastic oligoastrocytoma; untreated childhood anaplastic oligodendroglioma; recurrent childhood astrocytoma; other tumor of glial origin; 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 visual pathway; untreated childhood gliomatosis cerebri; untreated childhood oligodendroglioma; untreated childhood giant cell glioblastoma; untreated childhood glioblastoma; minimally differentiated myeloid leukemia (M0); myeloblastic leukemia with maturation (M2); myeloblastic leukemia without maturation (M1)
• Additional Relevant MeSH Terms: Body Weight; Body Weight Changes; Weight Loss; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Dermatologic Agents; Serotonin Agents; Serotonin Antagonists; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Cyproheptadine
• Other Study ID Numbers: SCUSF 0703; 5U10CA081920-11 (U.S. NIH Grant/Contract); SCUSF-0703 (Other Identifier: SunCoast CCOP Research Base)