Clinical trial NCT01132547: Cyproheptadine in Preventing Weight Loss in Children Receiving Chemotherapy for Cancer
Official title: Prevention of Cancer/Treatment-Related Weight Loss in Children at High Nutritional Risk
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Cancer
Keywords: 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
Lead sponsor: University of South Florida
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2010-05-28
Enrollment: 22
Sex: ALL
Minimum age (years): 2
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Participant With Weight Loss ≥ 5% at the 8- Week Assessment When Compared to Baseline
timeFrame: 8 weeks
measure: Severity of Weight Loss
timeFrame: Baseline and 8 weeks
Secondary outcomes:
measure: Pattern of Weight in the Study Population
timeFrame: Baseline and 8 weeks
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Miller Children's Hospital
state: California
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Wilmington
country: United States
facility: A.I. duPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Fort Myers
country: United States
facility: Children's Hospital of Southwest Florida at Lee Memorial
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Clinic - Jacksonville
state: Florida
city: Orlando
country: United States
facility: Arnold Palmer Hospital for Children
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Clinic - Orlando
state: Florida
city: Pensacola
country: United States
facility: Nemours Children's Hospital Pensacola
state: Florida
city: Honolulu
country: United States
facility: Kapiolani Medical Center for Women and Children
state: Hawaii
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: San Antonio
country: United States
facility: CHRISTUS Santa Rosa Children's Hospital
state: Texas
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
Study officials:
affiliation: University of South Florida
name: Jeffrey P. Krischer, PhD
role: PRINCIPAL_INVESTIGATOR
References: