Cyproheptadine in Preventing Weight Loss in Children Receiving Chemotherapy for Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Cancer

Intervention / Treatment
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* Drug: cyproheptadine hydrochloride
* Other: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I cyproheptadine hydrochloride<br>Patients receive oral cyproheptadine hydrochloride twice daily for 8 weeks. | Drug: cyproheptadine hydrochloride<br>* Given orally<br>* Other names: cyproheptadine HCl;|
| Placebo Comparator: Arm II placebo<br>Patients receive an oral placebo twice daily for 8 weeks. | Other: placebo<br>* Given orally<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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