Adderall XR Compared With Concerta in Treating Young Cancer Patients With Memory, Attention, and Depression

Adderall-XR Versus Concerta For Cancer Treatment-Related Neurocognitive Sequelae And Depression In Pediatric Patients: A Randomized Phase II Study

RATIONALE: Stimulant drugs such as dextroamphetamine-amphetamine and methylphenidate may help improve memory, attention, and thinking problems caused by central nervous system (CNS) treatment for cancer, and may help decrease depression.

PURPOSE: This randomized phase II trial is studying dextroamphetamine-amphetamine to see how well it works compared to methylphenidate in treating depression and problems with memory, attention, and thinking in children who have undergone CNS treatment for cancer. This trial will also study how often depression is seen and if these medications might help.

Study Overview

• Status: Terminated
• Conditions: Depression; Unspecified Childhood Solid Tumor, Protocol Specific; Neurotoxicity
• Intervention / Treatment: Drug: Adderall-XR®; Drug: Concerta®

Detailed Description

OBJECTIVES:

• Compare the response rates in pediatric cancer patients with treatment-related neurocognitive sequelae treated with dextroamphetamine-amphetamine (Adderall-XR®) vs methylphenidate (Concerta®).
• Compare the durability of response at 12 weeks in patients who show a response at 3 weeks after treatment with these drugs.
• Determine whether patients who have no response to one of these study drugs can respond to the other study drug.
• Determine the prevalence of depression and possible response to neurostimulant therapy in this patient population.

OUTLINE: This is a randomized, multicenter study.

Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral dextroamphetamine-amphetamine once daily for 3 weeks. Patients who achieve response (based on neurocognitive testing) continue treatment for a total of 12 weeks. Patients with no response after 3 weeks cross over to arm II after a 48-hour washout period.
• Arm II: Patients receive oral methylphenidate once daily for 3 weeks. Responding patients continue treatment for a total of 12 weeks. Patients with no response after 3 weeks cross over to arm I after a 48-hour washout period.

Depression and neurocognitive function are assessed at baseline, 3 weeks, and end of study.

PROJECTED ACCRUAL: A total of 177 patients (approximately 88 per treatment arm) will be accrued for this study within 3 years.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610-0296
      • University of Florida Shands Cancer Center
    • Pensacola, Florida, United States, 32504
      • Sacred Heart 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
  • Georgia
    • Augusta, Georgia, United States, 30912-4000
      • MBCCOP-Medical College of Georgia Cancer Center
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital - Royal Oak Campus
  • Texas
    • Lackland Air Force Base, Texas, United States, 78236-5300
      • Wilford Hall Medical Center
    • San Antonio, Texas, United States, 78207
      • Christus Santa Rosa Children's Hospital
    • San Antonio, Texas, United States, 78229-3900
      • MBCCOP - South Texas Pediatrics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA:

• Between the ages of 6-17 at the time of study participation.
• Have a diagnosis of any malignancy that required CNS treatment such as surgery and/or irradiation and/or intrathecal chemotherapy. (Patients treated with systemic chemotherapy alone are not eligible to participate)
• Off treatment and cancer free for a minimum of 6 months.
• Have a proficiency in English.

EXCLUSION CRITERIA:

• Patients with an estimated intelligence quotient (IQ) of less than 65 (based on the Wide Range Achievement Test (WRAT-3) Reading subtest) are not eligible to continue on study.
• At least one standard deviation below the level of performance predicted by their IQ on at least 2 of the 3 WISC-III subtests.
• Diagnosed with Attention Deficit Disorder (ADD) or Attention Deficit Hyperactivity Disorder (ADHD) prior to their cancer diagnosis.
• Currently taking antidepressants, antipsychotics, or other stimulants.
• Are blind.
• Have glaucoma.
• Family history of motor and phonic tics or Tourette's syndrome.
• Have seizures not controlled by antiepileptic drugs. (Note: Patients who are not experiencing seizure activity, having been on a stable dose of an antiepileptic drug for at least 12 weeks may participate)
• Taking a monoamine oxidase (MAO) inhibitor.
• Have a history of cardiovascular disease, uncontrolled hypertension or hyperthyroidism.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1- Adderall- XR®; Adderall-XR® 1 10 mg/day for 3-12 weeks depending on subject's response	Drug: Adderall-XR®; Adderall-XR® 10 mg/day for 3-12 weeks depending on subject's response; Other Names: dextroamphetamine-amphetamine; Drug: Concerta®; Concerta® 18 mg/day for 3-12 weeks depending on subject's response; Other Names: methylphenidate hydrochloride
Experimental: Arm II Concerta®; Concerta ® 18 mg/day for 3-12 weeks depending on subject's response	Drug: Adderall-XR®; Adderall-XR® 10 mg/day for 3-12 weeks depending on subject's response; Other Names: dextroamphetamine-amphetamine; Drug: Concerta®; Concerta® 18 mg/day for 3-12 weeks depending on subject's response; Other Names: methylphenidate hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response rate as measured by Wechsler Intelligence Scale for Children-III (WISC III) subtest: Coding, Symbol Search and Digit Span at baseline, and 3 weeks after the start of study treatment	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Durability of response as measured by WISC III subtest: Coding, Symbol Search and Digit Span at 12 weeks after the start of study treatment	12 weeks
Depression as measured by Children's Depression Inventory Short Version (CDI-S) at baseline, weeks 3 and 12	12 weeks

Collaborators and Investigators

• Sponsor: University of South Florida
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Margaret Booth-Jones, PhD, University of South Florida

Study record dates

Study Major Dates

• Study Start: August 1, 2003
• Primary Completion (Actual): June 1, 2006
• Study Completion (Actual): September 1, 2006

Study Registration Dates

• First Submitted: October 3, 2003
• First Submitted That Met QC Criteria: October 6, 2003
• First Posted (Estimate): October 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: unspecified childhood solid tumor, protocol specific; depression; neurotoxicity
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Chemically-Induced Disorders; Nervous System Diseases; Mood Disorders; Poisoning; Depression; Depressive Disorder; Neurotoxicity Syndromes; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Sympathomimetics; Adrenergic Uptake Inhibitors; Methylphenidate; Amphetamine; Dextroamphetamine; Adderall
• Other Study ID Numbers: SCUSF 0201; HLMCC-0201 (Other Identifier: H. Lee Moffitt Cancer Center Research Base); U10CA081920 (U.S. NIH Grant/Contract); SCUSF-0201 (Other Identifier: SunCoast CCOP Research Base)