Trial of a Sustained Release Methylphenidate in the Treatment of Fatigue in Cancer Patients
Study Details
Study Description
Brief Summary
The goal of this clinical research study is to see if the drug OROS Methylphenidate HCl (Concerta) can help to control fatigue in patients with breast, gastrointestinal, lymphoma, myeloma or lung cancer who are going through chemotherapy or hormonal treatment or have completed chemotherapy or hormonal treatment in the last 12 months. The safety of this drug will also be studied. Another goal of the study is to see how certain cytokines change while patients undergo chemotherapy or hormonal treatment.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
OROS Methylphenidate HCl is a mild central nervous system stimulant. Cytokines are a type of protein found in blood. Medical researchers here at M. D. Anderson are working to see if they are related to, or can tell us something about, fatigue and its symptoms.
This study will be divided into two, 14-day periods. During one of the 14-day periods, you will be given the study drug. During the other period, you will be given a placebo. A placebo is a sugar tablet that looks just like the study drug tablet.
You will be randomly picked (as in the toss of a coin) to be in one of two treatment groups. In one group you will receive the study drug first and the placebo second. In the other group you receive the placebo first and the study drug second. The chance of being in either treatment group is about equal. Neither you nor the research staff will know which treatment order you are assigned to.
Before treatment starts, you will fill out questionnaires about your level of fatigue, distress, symptoms, and general health. It should take about 5 minutes to complete the questionnaires. You will have a medical history, physical exam (with pulse, temperature, blood pressure), and blood work done. At the start of the study a test of the heart called an EKG will be done. At the start of the study, and after you finish the study, you will complete additional questionnaires that measure mood, fatigue, sleep, and appetite. It should take about 15 minutes to complete the questionnaires. You will also complete a series of tests for memory, visual-motor, and thinking functions. These tests should take about 30 minutes to complete. (This evaluation may take place on or before Day 1 of the study.)
On Day 1, a set of study medications and a diary will be given to you. For the first fourteen days of the study, you will take the assigned study medication (either drug or placebo). Everyday you will fill out the diary, noting the time you took the study medication and answering two questions about your fatigue.
On Day 7, study personnel will see you in the clinic or Ambulatory Treatment Center. The delegated research personnel will take your blood pressure and pulse and ask you about any symptoms or complaints you may have had or any medications you may have taken.
On Day 14, study personnel will see you in the clinic or the Ambulatory Treatment Center where blood pressure and pulse will be measured. Unused study medication will be returned and your diary will be reviewed with the delegated research personnel. You will complete questionnaires asking about fatigue, sleep, depression, and symptoms. It should take about 15 minutes to complete them. You will also complete a series of tests for memory, visual-motor, and thinking functions. The tests should take about 30 minutes to complete. A blood draw will be done to look for changes in hemoglobin and for cytokine analysis.
A new set of study medications and a diary will be given to you. You will follow the same instructions as the first time period. You will take the assigned study medication every morning and fill out the diary, noting the time you took the study medication and answering two questions about your fatigue.
On Day 21, the same activities as Day 7 will occur.
If you are not scheduled to come to M. D. Anderson on Day 7 and Day 21, you will take 2 separate blood pressure measurements 5 minutes apart for each day and report results within 24 hours to the research staff. If you choose to take your blood pressure measurements at home, you need to bring your monitor at study enrollment to have measurements double-checked by research staff.
On Day 28, the study will end. The same activities as Day 14 will occur. In addition, you will have a physical exam.
You will be asked if you prefer the first (first 2 weeks of study) or second (second 2 weeks of study) treatment phase. If you want to continue taking the OROS Methylphenidate you will be allowed to do so off-study as long as there are no medical reasons not to.
This is an investigational study. The study drug has been approved for attention-deficit hyperactivity disorder but is investigational as a treatment for cancer related fatigue. The study medication and physical exams will cost you nothing. You will be reimbursed with a fixed amount of money for each scheduled study visit. The payment will be in the form of a gift card for parking expenses and a gift card for gas expenses. The study doctor or study staff can tell you more about when you will be able to receive reimbursement. A total of 50 patients will take part in this study. All will be enrolled at The University of Texas (UT) MD Anderson.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Methylphenidate then Placebo Methylphenidate 18 mg oral daily for 2 weeks then Placebo oral daily for 2 weeks |
Drug: Methylphenidate
18 mg by mouth daily for 2 weeks
Other Names:
Drug: Placebo
Capsule by mouth daily for 2 weeks
|
| Experimental: Placebo then Methylphenidate Placebo oral daily for 2 weeks then Methylphenidate 18 mg oral daily for 2 weeks |
Drug: Methylphenidate
18 mg by mouth daily for 2 weeks
Other Names:
Drug: Placebo
Capsule by mouth daily for 2 weeks
|
Outcome Measures
Primary Outcome Measures
- Mean Difference Between Post-Methylphenidate and Post-Placebo Measurement [At end of two 2-week treatment cycles (4 weeks total)]
The primary endpoint is the "fatigue worst" score (range: 0 - 10) on the Brief Fatigue Inventory (BFI) at the end of two-week treatment (either Methylphenidate or placebo). "Worst fatigue" is defined as participants' rating of worst fatigue on a scale of 0 (no fatigue) to 10 (as bad as can imagine). Since each participant is expected to receive both 2-week of Methylphenidate or 2-week placebo at different times, they serve as their own control. The outcome is the difference in "fatigue worst" score between post-Methylphenidate measurement and post-Placebo measurement.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patient diagnosed with breast, gastrointestinal, lymphoma, myeloma or lung cancer undergoing chemotherapy or hormonal treatment
-
Patient is > or = 18 years of age
-
Patient has Brief Fatigue Inventory "fatigue worst" score of > or = 4 at baseline
-
Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of < or = 2 at baseline
-
Patient has a life expectancy > or = 6 months from the start of the study
-
Patient is using acceptable birth control methods. Female participants (if of child bearing potential and sexually active) and male participants (if sexually active with a partner of child-bearing potential) must use medically acceptable methods of birth control. Medically acceptable methods of contraception include abstinence, birth control pills, diaphragm with spermicide, condom with foam or spermicide, vaginal spermicidal suppository or surgical sterilization
-
Patient must speak and understand English
-
Patient has provided written informed consent to participate in the study prior to enrollment to the study
Exclusion Criteria:
-
History of hypersensitivity reaction to methylphenidate
-
History of or current seizure disorder, glaucoma, major psychiatric diagnosis, narcolepsy, Tourette's syndrome, tension or agitation
-
History of clinically significant cardiac disease.
-
Uncontrolled hypertension: has not been on a stable treatment dose for the past month, or has a systolic pressure consistently (defined as 3 consecutive blood pressure readings within the last 30 days) greater than 150 mm Hg or diastolic pressure consistently greater than 85 mm Hg
-
History of fibromyalgia
-
Use of alcohol while participating in the study
-
Current use of illicit drugs or history of alcohol or drug abuse and/or abuse potential (see protocol for criteria)
-
Moderate to severe depression (> or = 20 on Beck Depression Index II)
-
If taking antidepressants, no changes in dose and/or no start of new course of treatment in the last 30 days
-
Currently taking psychostimulants (including appetite suppressants), monoamine oxidase (MAO) inhibitors, anticoagulant or anticonvulsant therapy
-
Current use of corticosteroids, medications, or stimulants (i.e., vivarin) used to improve fatigue symptoms
-
Use of an investigational medication within the past month
-
Current use of the following herbals or supplements for fatigue relief (DHEA, SAME, ginkgo, ginseng, St. John's Wort (including DHEA, SAME, ginkgo, ginseng, St. John's Wort, metabolite, effedrin, basil, citronella, fennel, horseradish roots, lavender flowers, lemon verbena, marjoram, mint, nettle, pine needles, rosemary, sage, savory, thyme, bay, cayenne pepper, cinnamon, eucalyptus, hyssop, myrrh, oregano, peppermint, ginseng, green, black or Chinese tea, ephedra (aka - ma-huang), popotillo, and Mormon tea)
-
Any coexisting medical condition or are taking any concomitant medication that is likely to interfere with the safe administration of methylphenidate
-
Patients who start epoetin within 30 days prior to enrollment
-
Patients who start taking epoetin during the first week of the study
-
Hemoglobin < 8.0 gm/dl
-
Patients with a thyroid-stimulating hormone (TSH) value > or = 1.5 times the upper limit of normal (ULN)
-
Albumin value 50% lower than the lower limit of normal
-
Evidence of hepatic impairment [total bilirubin > or = 2.5 times ULN (normal range of 0 - 1.0 mg/dl, serum glutamate pyruvate transaminase (SGPT) > or = 2.5 times ULN)]
-
Evidence of renal impairment (serum creatinine > 2.5 times ULN, normal range of 0.8 - 1.5 mg/dl)
-
A severe narrowing (pathological or iatrogenic), obstruction of the gastrointestinal tract, or gastrointestinal malabsorption
-
If taking anxiolytics, and/or hypnotics, no changes in dose and/or no start of new course of treatment in the last 30 days
-
Patients with nausea, vomiting, or diarrhea of Common Toxicity Criteria for Adverse Effects (CTCAE) grade III or higher
-
If taking anticonvulsants for sensory neuropathy (Gabapentin or Pregabalin), no changes in dose and/or no start of new course of treatment in the last 30 days
-
History of severe headaches within 30 days prior to enrollment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UT MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
- Ortho-McNeil Janssen Scientific Affairs, LLC
Investigators
- Principal Investigator: Carmen Escalante, MD, M.D. Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- ID00-372
Study Results
Participant Flow
| Recruitment Details | Recruitment Period: 03/11/2005 to 03/23/2011. All participants were recruited at UT MD Anderson Cancer Center. |
|---|---|
| Pre-assignment Detail | Participants were randomized to receive methylphenidate-placebo or placebo-methylphenidate. Of the 42 enrolled: 33 completed the study + 4 completed partial visits + 1 randomized to placebo twice (38 total), excluded were three who did not meet criteria (not randomized), and one who withdrew consent. |
| Arm/Group Title | Methylphenidate Then Placebo | Placebo Then Methylphenidate |
|---|---|---|
| Arm/Group Description | Methylphenidate 18 mg oral daily for 2 weeks then Placebo oral daily for 2 weeks | Placebo oral daily for 2 weeks then Methylphenidate 18 mg oral daily for 2 weeks |
| Period Title: Overall Study | ||
| STARTED | 19 | 19 |
| COMPLETED | 17 | 16 |
| NOT COMPLETED | 2 | 3 |
Baseline Characteristics
| Arm/Group Title | Methylphenidate Then Placebo | Placebo Then Methylphenidate | Total |
|---|---|---|---|
| Arm/Group Description | 18 mg Oral Daily for 2 Weeks Placebo : Capsule By Mouth Daily x 2 Weeks Methylphenidate : 18 mg By Mouth Daily x 2 Weeks | Placebo : Capsule By Mouth Daily x 2 Weeks Methylphenidate : 18 mg By Mouth Daily x 2 Weeks | Total of all reporting groups |
| Overall Participants | 19 | 19 | 38 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
17
89.5%
|
19
100%
|
36
94.7%
|
| >=65 years |
2
10.5%
|
0
0%
|
2
5.3%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
53.26
(11.95)
|
51.52
(7.83)
|
52.35
(9.88)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
19
100%
|
19
100%
|
38
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
19
100%
|
19
100%
|
38
100%
|
Outcome Measures
| Title | Mean Difference Between Post-Methylphenidate and Post-Placebo Measurement |
|---|---|
| Description | The primary endpoint is the "fatigue worst" score (range: 0 - 10) on the Brief Fatigue Inventory (BFI) at the end of two-week treatment (either Methylphenidate or placebo). "Worst fatigue" is defined as participants' rating of worst fatigue on a scale of 0 (no fatigue) to 10 (as bad as can imagine). Since each participant is expected to receive both 2-week of Methylphenidate or 2-week placebo at different times, they serve as their own control. The outcome is the difference in "fatigue worst" score between post-Methylphenidate measurement and post-Placebo measurement. |
| Time Frame | At end of two 2-week treatment cycles (4 weeks total) |
Outcome Measure Data
| Analysis Population Description |
|---|
| It is a crossover design and only the 33 patients who completed the study were included in the final data analysis. |
| Arm/Group Title | Methylphenidate | Placebo |
|---|---|---|
| Arm/Group Description | Methylphenidate 18 mg oral daily for 2 Weeks preceded or followed by Placebo oral daily for 2 weeks. | Placebo taken oral daily for 2 Weeks. |
| Measure Participants | 33 | 33 |
| Mean (Standard Deviation) [units on a scale] |
5.18
(2.52)
|
4.76
(2.68)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Methylphenidate, Placebo |
|---|---|---|
| Comments | As a crossover study, the potential carryover effect was examined first. The pooled data (the 2-week treatment for each intervention i.e. period 1 & period 2) was used to assess the treatment effect (A versus B). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.54 |
| Comments | ||
| Method | Wilcoxon signed rank test | |
| Comments | ||
| Method of Estimation | Estimation Parameter | mean difference in treat versus control |
| Estimated Value | 0.42 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 3.3 |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Adverse events were collected for entire study period of 4 weeks. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Methylphenidate Then Placebo | Placebo Then Methylphenidate | ||
| Arm/Group Description | 18 mg Oral Daily for 2 Weeks Placebo : Capsule By Mouth Daily x 2 Weeks Methylphenidate : 18 mg By Mouth Daily x 2 Weeks | Placebo : Capsule By Mouth Daily x 2 Weeks Methylphenidate : 18 mg By Mouth Daily x 2 Weeks | ||
All Cause Mortality |
||||
| Methylphenidate Then Placebo | Placebo Then Methylphenidate | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Methylphenidate Then Placebo | Placebo Then Methylphenidate | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/19 (0%) | 1/19 (5.3%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 0/19 (0%) | 0 | 1/19 (5.3%) | 1 |
| Infections and infestations | ||||
| Neutropenic fever | 0/19 (0%) | 0 | 1/19 (5.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Methylphenidate Then Placebo | Placebo Then Methylphenidate | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/19 (36.8%) | 5/19 (26.3%) | ||
| Blood and lymphatic system disorders | ||||
| Nose bleed | 0/19 (0%) | 0 | 1/19 (5.3%) | 1 |
| Cardiac disorders | ||||
| Palpitations | 1/19 (5.3%) | 1 | 0/19 (0%) | 0 |
| Sinus tachycardia | 0/19 (0%) | 0 | 1/19 (5.3%) | 1 |
| Gastrointestinal disorders | ||||
| Dry mouth | 0/19 (0%) | 0 | 1/19 (5.3%) | 1 |
| Abdominal discomfort | 1/19 (5.3%) | 1 | 1/19 (5.3%) | 1 |
| Vomiting | 0/19 (0%) | 0 | 1/19 (5.3%) | 1 |
| Diarrhea | 0/19 (0%) | 0 | 1/19 (5.3%) | 1 |
| Nausea | 1/19 (5.3%) | 1 | 0/19 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Generalized weakness | 0/19 (0%) | 0 | 1/19 (5.3%) | 1 |
| Nervous system disorders | ||||
| Anxiety | 1/19 (5.3%) | 1 | 0/19 (0%) | 0 |
| Insomnia | 1/19 (5.3%) | 1 | 0/19 (0%) | 0 |
| Headache | 2/19 (10.5%) | 2 | 1/19 (5.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Sinus congestion | 1/19 (5.3%) | 1 | 1/19 (5.3%) | 1 |
| Cough | 0/19 (0%) | 0 | 1/19 (5.3%) | 1 |
| Upper respiratory infection | 1/19 (5.3%) | 1 | 2/19 (10.5%) | 2 |
| Allergic rhinitis | 1/19 (5.3%) | 1 | 0/19 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Rash/desquamation | 0/19 (0%) | 0 | 1/19 (5.3%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Carmen Escalante, MD / Professor |
|---|---|
| Organization | UT MD Anderson Cancer Center |
| Phone | |
| RABaker@mdanderson.org |
- ID00-372