Cyproheptadine and Megestrol in Preventing Weight Loss in Children With Cachexia Caused By Cancer or Cancer Treatment

• ClinicalTrials.gov Identifier: NCT00066248
• Recruitment Status: Completed
• First Posted: August 7, 2003
• Last Update Posted: February 3, 2014
• Sponsor: University of South Florida
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): University of South Florida

Study Description

Brief Summary:

RATIONALE: Cyproheptadine and megestrol may improve appetite and help prevent weight loss in children with cancer.

PURPOSE: This phase II trial is studying how well cyproheptadine and megestrol work in improving appetite and preventing weight loss in children with cachexia caused by cancer or cancer treatment.

Condition or disease	Intervention/treatment	Phase
Brain Tumor; Central Nervous System Tumors; Cachexia; Leukemia; Lymphoma; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases; Unspecified Childhood Solid Tumor, Protocol Specific	Drug: cyproheptadine hydrochloride; Drug: megestrol acetate	Phase 2

Detailed Description:

OBJECTIVES:

• Determine the efficacy of cyproheptadine in preventing further weight loss in children with cancer or cancer treatment-related cachexia.
• Determine the efficacy of megestrol in preventing further weight loss in patients who don't respond to cyproheptadine.
• Determine how these drugs affect body protein and fat levels in these patients.

OUTLINE: Patients receive oral cyproheptadine twice daily for 4 weeks in the absence of unacceptable weight loss or toxicity. Patients that present with weight loss after 4 weeks receive oral megestrol daily for 4 weeks in the absence of unacceptable weight loss or toxicity. Patients responding to either cyproheptadine or megestrol may continue treatment at the discretion of the treating physician.

Patients are followed at 4 weeks.

PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 70 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: The Effect of Cyproheptadine Hydrochloride (Periactin) and Megestrol Acetate (Megace) on Weight in Children With Cancer/Treatment Related Cachexia
• Study Start Date: June 2003
• Actual Primary Completion Date: August 2007
• Actual Study Completion Date: August 2007

Arms and Interventions

Arm	Intervention/treatment
Experimental: Subjects that respond to Periactin; Receive 0.25mg/kg cyproheptadine hydrochloride once daily for 4 weeks. If subject responds to treatment (stable or increased weigh), go off study. If subject does not respond (loses weigh), subject will switch to10 mg/lg/day of megestrol acetate for 4 weeks.	Drug: cyproheptadine hydrochloride; Receive 0.25mg/kg cyproheptadine hydrochloride once daily for 4 weeks. If subject responds to treatment (stable or increased weigh), go off study. If subject does not respond (loses weigh), subject will switch to10 mg/lg/day of megestrol acetate for 4 weeks.; Other Name: Periactin
Experimental: Non-responders to Periactin- Megace Arm; Receive 0.25mg/kg cyproheptadine hydrochloride once daily for 4 weeks. If subject responds to treatment (stable or increased weigh), go off study. If subject does not respond (loses weigh), subject will switch to10 mg/lg/day of megestrol acetate for 4 weeks.	Drug: cyproheptadine hydrochloride; Receive 0.25mg/kg cyproheptadine hydrochloride once daily for 4 weeks. If subject responds to treatment (stable or increased weigh), go off study. If subject does not respond (loses weigh), subject will switch to10 mg/lg/day of megestrol acetate for 4 weeks.; Other Name: Periactin; Drug: megestrol acetate; Receive 0.25mg/kg cyproheptadine hydrochloride once daily for 4 weeks. If subject responds to treatment (stable or increased weigh), go off study. If subject does not respond (loses weigh), subject will switch to10 mg/lg/day of megestrol acetate for 4 weeks.; Other Name: Megace

Outcome Measures

Primary Outcome Measures :

1. Efficacy of study agents as measured by changes in weight at baseline, and 4 weeks after the beginning of study treatment [ Time Frame: 4-8 weeks ]

Secondary Outcome Measures :

1. Effect of study agents on protein and fat levels as measured by pre-albumin and lipid profile at baseline, and 4 weeks after the beginning of study treatment [ Time Frame: 4-8 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 20 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

INCLUSION CRITERIA:

• Any cachectic patient with weight loss presumed secondary to cancer or cancer related therapy is eligible. Cachexia is defined as having one or more of the following:
• documented history of weight loss > 5%
• drop in growth rate two or more percentile ranks on standard growth charts,
• weight for height less than the tenth percentile.
• Patients with newly diagnosed or relapsed cancer of any type, including brain tumors.
• Patients who are receiving active or palliative therapy are eligible.
• If patients have completed treatment for cancer (surgery, chemotherapy, radiotherapy) within 8 weeks of study registration, they are also eligible.
• Patients must be ≥ 2 years and < 21 years of age at the time of admission to this study.
• Patients must have a predicted life expectancy of at least eight weeks.

EXCLUSION CRITERIA:

• Patients who are currently taking or who have taken Periactin and/or Megace during the past three weeks are not eligible.
• Patients receiving corticosteroid or monoamine oxidase (MAO) inhibitor therapy. (Intermittent steroid use is permitted IF you anticipate it will not be administered for more than 7 days in a 4 week period. Calculate anticipated intermittent steroid use in 4-week intervals through the 8-week period during which study agent may be administered (4 weeks for Periactin and potentially 4 weeks for Megace.
• Patients who have received parenteral nutrition or tube feedings within 1 week of starting this protocol or patients who are expected to require parenteral nutrition or tube feedings during the 4-week course of this study.
• Patients taking dronabinol (Marinol) or other appetite-stimulating medications during the past three weeks or patients expected to be prescribed appetite-stimulating medications during the 4-week course of this study.
• Patients with hormone sensitive tumors specifically meningiomas, breast cancer, ovarian cancer, and endometrial carcinoma.31, 32
• Children with neurofibromatosis, type I or II, are at risk for the development of meningiomas and are thus excluded from this study.32
• Children with glaucoma, chronic persistent asthma, or gastrointestinal (GI) or genitourinary (GU) obstruction.
• Patients with recurrent and/or persistent hypertension, defined as blood pressure values >20% above normal.
• Patients with thromboembolic disease, congestive heart failure, or peripheral edema.
• Patients who are pregnant.

Contacts and Locations

  Show 43 Study Locations

Sponsors and Collaborators

University of South Florida

National Cancer Institute (NCI)

Investigators

• Study Chair: Jennifer L. Mayer, MD; H. Lee Moffitt Cancer Center and Research Institute

More Information

Publications of Results:

Couluris M, Mayer JL, Freyer DR, Sandler E, Xu P, Krischer JP. The effect of cyproheptadine hydrochloride (periactin) and megestrol acetate (megace) on weight in children with cancer/treatment-related cachexia. J Pediatr Hematol Oncol. 2008 Nov;30(11):791-7. doi: 10.1097/MPH.0b013e3181864a5e.

• Responsible Party: University of South Florida
• ClinicalTrials.gov Identifier: NCT00066248 History of Changes
• Other Study ID Numbers: SCUSF 0205; HLMCC-0205 ( Other Identifier: H. Lee Moffitt Cancer Center Research Base ); U10CA081920 ( U.S. NIH Grant/Contract ); SCUSF 0205 ( Other Identifier: SunCoast CCOP Research Base )
• First Posted: August 7, 2003
• Last Update Posted: February 3, 2014
• Last Verified: January 2014

Keywords provided by University of South Florida:

cachexia; unspecified childhood solid tumor; childhood spinal cord neoplasm; recurrent childhood medulloblastoma; untreated childhood medulloblastoma; childhood high-grade cerebral astrocytoma; childhood low-grade cerebral astrocytoma; recurrent childhood cerebellar astrocytoma; recurrent childhood cerebral astrocytoma; untreated childhood cerebellar astrocytoma; childhood oligodendroglioma; recurrent childhood brain stem glioma; recurrent childhood visual pathway glioma; hypothalamic glioma; untreated childhood brain stem glioma; untreated childhood visual pathway; childhood supratentorial primitive neuroectodermal tumor; childhood craniopharyngioma; childhood infratentorial ependymoma; childhood supratentorial ependymoma; newly diagnosed childhood ependymoma; recurrent childhood ependymoma; childhood choroid plexus tumor; childhood central nervous system germ cell tumor; 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

Additional relevant MeSH terms:

Lymphoma; Leukemia; Preleukemia; Brain Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Wasting Syndrome; Syndrome; Cachexia; Neoplasms; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease; Pathologic Processes; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Emaciation; Weight Loss; Body Weight Changes