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

University of South Florida

Status and phase: Completed; Phase 2

Conditions: Central Nervous System Tumors; Brain Tumor; Cachexia; Lymphoma; Leukemia; Myelodysplastic/Myeloproliferative Diseases; Myelodysplastic Syndromes; Unspecified Childhood Solid Tumor, Protocol Specific

Treatments: Drug: megestrol acetate; Drug: cyproheptadine hydrochloride

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00066248

HLMCC-0205 (Other Identifier)

SCUSF 0205 (Other Identifier)

U10CA081920 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 70 patients

Sex: All

Ages: 2 to 20 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Supportive Care

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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70 participants in 2 patient groups

Subjects that respond to Periactin

Experimental group

Description:

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.

Treatment:

Drug: cyproheptadine hydrochloride

Non-responders to Periactin- Megace Arm

Experimental group

Description:

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.

Treatment:

Drug: megestrol acetate

Drug: cyproheptadine hydrochloride