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

The Effect of Cyproheptadine Hydrochloride (Periactin) and Megestrol Acetate (Megace) on Weight in Children With Cancer/Treatment Related Cachexia

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.

Study Overview

• Status: Completed
• Conditions: Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific; Myelodysplastic Syndromes; Leukemia; Brain Tumor; Cachexia; Myelodysplastic/Myeloproliferative Diseases; Central Nervous System Tumors
• Intervention / Treatment: Drug: cyproheptadine hydrochloride; Drug: megestrol acetate

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 Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Hopital Sainte Justine
    • Montreal, Quebec, Canada, H3G 1A4
      • Montreal Children's Hospital at McGill University Health Center
• Puerto Rico
  • Santurce, Puerto Rico, 00912
    • San Jorge Children's Hospital
• United States
  • California
    • Oakland, California, United States, 94609-3305
      • CCOP - Bay Area Tumor Institute
    • Oakland, California, United States, 94609
      • Children's Hospital & Research Center Oakland
  • District of Columbia
    • Washington, District of Columbia, United States, 20010-2970
      • Children's National Medical Center
  • Florida
    • Gainesville, Florida, United States, 32610-0296
      • University of Florida Shands Cancer Center
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic
    • Pensacola, Florida, United States, 32504
      • Sacred Heart Cancer Center at Sacred Heart Hospital
    • St. Petersburg, Florida, United States, 33701
      • All Children's Hospital
    • Tampa, Florida, United States, 33677-4227
      • St. Joseph's Children's Hospital of Tampa
    • Tampa, Florida, United States, 33682-7757
      • CCOP - Florida Pediatric
    • West Palm Beach, Florida, United States, 33407
      • Kaplan Cancer Center at St. Mary's Medical Center
  • Georgia
    • Augusta, Georgia, United States, 30912-4000
      • MBCCOP - Medical College of Georgia Cancer Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Cancer Research Center of Hawaii
  • Kansas
    • Kansas City, Kansas, United States, 66160-7357
      • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70118
      • Children's Hospital of New Orleans
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Floating Hospital for Children at Tufts - New England Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48236
      • Van Elslander Cancer Center at St. John Hospital and Medical Center
    • Grand Rapids, Michigan, United States, 49503
      • DeVos Children's Hospital
    • Royal Oak, Michigan, United States, 48073-6769
      • CCOP - Beaumont
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Cancer Center
    • Saint Paul, Minnesota, United States, 55106-2049
      • Children's Hospitals and Clinics of Minnesota - Minneapolis
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Tomorrows Children's Institute at Hackensack University Medical Center
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28232-2861
      • Blumenthal Cancer Center at Carolinas Medical Center
    • Winston-Salem, North Carolina, United States, 27157-1096
      • Wake Forest University Comprehensive Cancer Center
  • Ohio
    • Akron, Ohio, United States, 44308-1062
      • Children's Hospital Medical Center of Akron
    • Columbus, Ohio, United States, 43205-2696
      • Columbus Children's Hospital
    • Dayton, Ohio, United States, 45404-1815
      • Children's Medical Center - Dayton
    • Youngstown, Ohio, United States, 44501
      • Tod Children's Hospital
  • Oregon
    • Portland, Oregon, United States, 97227
      • Legacy Emanuel Hospital and Health Center & Children's Hospital
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Children's Hospital of Pittsburgh
  • Texas
    • San Antonio, Texas, United States, 78207
      • Christus Santa Rosa Children's Hospital
    • San Antonio, Texas, United States, 78229-3900
      • MBCCOP - South Texas Pediatrics
    • San Antonio, Texas, United States, 78229-3902
      • Methodist Cancer Center at Methodist Specialty and Transplant Hospital
    • Temple, Texas, United States, 76508
      • CCOP - Scott and White Hospital
  • Vermont
    • Burlington, Vermont, United States, 05405-0110
      • Vermont Cancer Center at University of Vermont
  • Virginia
    • Richmond, Virginia, United States, 23298-0121
      • Virginia Commonwealth University Massey Cancer Center
  • Washington
    • Seattle, Washington, United States, 98105-3916
      • Children's Hospital and Regional Medical Center - Seattle
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54307-9070
      • St. Vincent Hospital Regional Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 months to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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 Names: 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 Names: Megace

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Efficacy of study agents as measured by changes in weight at baseline, and 4 weeks after the beginning of study treatment	4-8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
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	4-8 weeks

Collaborators and Investigators

• Sponsor: University of South Florida
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Jennifer L. Mayer, MD, H. Lee Moffitt Cancer Center and Research Institute

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2003
• Primary Completion (Actual): August 1, 2007
• Study Completion (Actual): August 1, 2007

Study Registration Dates

• First Submitted: August 6, 2003
• First Submitted That Met QC Criteria: August 6, 2003
• First Posted (Estimate): August 7, 2003

Study Record Updates

• Last Update Posted (Estimate): February 3, 2014
• Last Update Submitted That Met QC Criteria: January 31, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: stage I chronic lymphocytic leukemia; untreated childhood brain stem glioma; childhood high-grade cerebral astrocytoma; stage III childhood small noncleaved cell lymphoma; stage IV childhood small noncleaved cell lymphoma; stage IV childhood large cell lymphoma; recurrent childhood small noncleaved cell lymphoma; recurrent childhood large cell lymphoma; chronic myelomonocytic leukemia; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; childhood acute lymphoblastic leukemia in remission; childhood acute myeloid leukemia in remission; juvenile myelomonocytic leukemia; chronic phase chronic myelogenous leukemia; childhood chronic myelogenous leukemia; atypical chronic myeloid leukemia; untreated childhood acute lymphoblastic leukemia; AIDS-related peripheral/systemic lymphoma; recurrent/refractory childhood Hodgkin lymphoma; blastic phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; cachexia; childhood supratentorial primitive neuroectodermal tumor; refractory chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; refractory hairy cell leukemia; recurrent childhood acute lymphoblastic leukemia; stage I childhood large cell lymphoma; stage II childhood large cell lymphoma; stage III childhood large cell lymphoma; stage I childhood lymphoblastic lymphoma; stage II childhood lymphoblastic lymphoma; stage III childhood lymphoblastic lymphoma; stage IV childhood lymphoblastic lymphoma; stage I childhood small noncleaved cell lymphoma; stage II childhood small noncleaved cell lymphoma; accelerated phase chronic myelogenous leukemia; untreated childhood medulloblastoma; untreated childhood cerebellar astrocytoma; childhood infratentorial ependymoma; newly diagnosed childhood ependymoma; stage IV childhood Hodgkin lymphoma; recurrent childhood acute myeloid leukemia; recurrent childhood lymphoblastic lymphoma; stage III childhood Hodgkin lymphoma; stage I childhood Hodgkin lymphoma; stage II childhood Hodgkin lymphoma; meningeal chronic myelogenous leukemia; childhood supratentorial ependymoma; childhood oligodendroglioma; recurrent childhood cerebellar astrocytoma; recurrent childhood cerebral astrocytoma; recurrent childhood ependymoma; recurrent childhood brain tumor; recurrent childhood brain stem glioma; recurrent childhood medulloblastoma; childhood craniopharyngioma; childhood central nervous system germ cell tumor; childhood choroid plexus tumor; progressive hairy cell leukemia, initial treatment; untreated hairy cell leukemia; AIDS-related primary CNS lymphoma; untreated childhood acute myeloid leukemia; other myeloid malignancies; childhood low-grade cerebral astrocytoma; recurrent childhood visual pathway glioma; myelodysplastic/myeloproliferative disease; childhood spinal cord neoplasm; unspecified childhood solid tumor; hypothalamic glioma; untreated childhood visual pathway
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms by Site; Disease; Bone Marrow Diseases; Hematologic Diseases; Nutrition Disorders; Body Weight; Body Weight Changes; Precancerous Conditions; Emaciation; Weight Loss; Neoplasms; Lymphoma; Syndrome; Myelodysplastic Syndromes; Leukemia; Preleukemia; Brain Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Wasting Syndrome; Cachexia; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Gastrointestinal Agents; Antineoplastic Agents, Hormonal; Dermatologic Agents; Serotonin Agents; Serotonin Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Contraceptives, Oral, Hormonal; Central Nervous System Stimulants; Appetite Stimulants; Cyproheptadine; Megestrol; Megestrol Acetate
• Other Study ID Numbers: SCUSF 0205 (Other Identifier: SunCoast CCOP Research Base); U10CA081920 (U.S. NIH Grant/Contract); HLMCC-0205 (Other Identifier: H. Lee Moffitt Cancer Center Research Base)