Dextroamphetamine-Amphetamine Compared With Methylphenidate in Treating Children Who Have Problems With Memory, Attention, Thinking, and Depression Caused By Cancer Treatment

Condition(s) targeted: Depression; Neurotoxicity; Unspecified Childhood Solid Tumor, Protocol Specific

Intervention: dextroamphetamine-amphetamine (Drug); methylphenidate hydrochloride (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: H. Lee Moffitt Cancer Center and Research Institute

Official(s) and/or principal investigator(s):
Margaret Booth-Jones, PhD, Study Chair, Affiliation: H. Lee Moffitt Cancer Center and Research Institute

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.

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

Study design: Supportive Care, Randomized, Active Control

Primary outcome: 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

Secondary outcome:

Durability of response as measured by WISC III subtest: Coding, Symbol Search and Digit Span at 12 weeks after the start of study treatment

Depression as measured by Children's Depression Inventory Short Version (CDI-S) at baseline, weeks 3 and 12

Detailed description: OBJECTIVES:

- Compare the response rates in pediatric cancer patients with treatment-related

neurocognitive sequelae treated with dextroamphetamine-amphetamine vs methylphenidate.

- 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.

Minimum age: 6 Years. Maximum age: 17 Years. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- Diagnosis of a malignancy and received prior CNS treatment (e. g., surgery and/or

radiotherapy and/or intrathecal chemotherapy)

- Patients treated with prior systemic chemotherapy alone are not eligible

- At least 6 months since prior treatment

- Cancer-free for at least 6 months

- Neurocognitive function at least 1 standard deviation below the level of performance

predicted by patient's IQ on at least 2 of 3 WISC®-III subtests*

- No diagnosis of attention deficit disorder or attention-deficit hyperactivity disorder

before cancer diagnosis NOTE: *Patients who are not eligible for randomization based on test results may be retested every 3 months

PATIENT CHARACTERISTICS:

Age

- 6 to 17

Performance status

- Not specified

Life expectancy

- Not specified

Hematopoietic

- Not specified

Hepatic

- Not specified

Renal

- Not specified

Cardiovascular

- No history of cardiovascular disease or uncontrolled hypertension

Other

- No history of hyperthyroidism

- Estimated IQ of at least 65 (based on the WRAT-3™ reading subtest)

- Not blind

- No glaucoma

- No family history of motor and phonic tics or Tourette's syndrome

- No seizures not controlled by antiepileptic drugs

- Patients not currently experiencing seizures and who have been on a stable dose

of antiepileptic drugs for at least 12 weeks are eligible

- Proficient in English

- Not pregnant or nursing

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- See Disease Characteristics

Endocrine therapy

- Not specified

Radiotherapy

- See Disease Characteristics

Surgery

- See Disease Characteristics

Other

- No concurrent antidepressants, antipsychotics, or other stimulants

- No concurrent monoamine oxidase inhibitors

CCOP - Florida Pediatric, Tampa, Florida 33682-7757, United States

Sacred Heart Children's Hospital, Pensacola, Florida 32504, United States

St. Joseph's Children's Hospital of Tampa, Tampa, Florida 33677-4227, United States

University of Florida Shands Cancer Center, Gainesville, Florida 32610-0296, United States

MBCCOP-Medical College of Georgia Cancer Center, Augusta, Georgia 30912-4000, United States

William Beaumont Hospital - Royal Oak Campus, Royal Oak, Michigan 48073, United States

CHRISTUS Santa Rosa Children's Hospital, San Antonio, Texas 78207, United States

MBCCOP - South Texas Pediatrics, San Antonio, Texas 78229-3900, United States

Wilford Hall Medical Center, Lackland Air Force Base, Texas 78236-5300, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: August 2003
Last updated: May 23, 2008