Breast Cancer, Neurotoxicity, Pain
Conditions
Keywords
pain, neurotoxicity, breast cancer
Brief summary
D-cycloserine may help lessen pain and other symptoms of peripheral neuropathy caused by chemotherapy. It is not yet known whether D-cycloserine is more effective than a placebo in treating peripheral neuropathy caused by chemotherapy. This randomized, double-blind, placebo-controlled clinical trial was designed to study D-cycloserine at 2 different doses to see how well each works compared to the other and to a placebo in treating cancer patients with peripheral neuropathy caused by chemotherapy.
Detailed description
This is a randomized, double-blind, placebo-controlled study. Initially, patients were randomized to 1 of 2 treatment arms (D-cycloserine 250 mg twice daily or placebo twice daily), and treated for up to 4 weeks in the absence of unacceptable toxicity. Later, the design was changed to randomize patients to 1 of 3 arms as follows: * D-cycloserine 50 mg twice daily for up to 12 weeks * D-cycloserine 200 mg twice daily for up to 12 weeks * Placebo twice daily for up to 12 weeks
Interventions
DRUGD-cycloserine
OTHERPlacebo
Sponsors
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients will be at least 18 years of age. * Patients will be experiencing moderate to severe peripheral neuropathic pain * Patients may be on chronic adjuvant pain medications such as antidepressants but must be on stable doses for at least one week prior to admission. * Patients may be taking concurrent opioids but they must be willing to allow us to monitor their opioid use while on the trial. * Patients must have chronic peripheral neuropathic pain will be defined as pain of 3 or more months duration which began in association with chemotherapy. * Patient's will have bilateral peripheral neuropathic pain symptoms primarily involving the feet * Patients must have breast cancer (any stage) * Patients must be able to read and speak English and provide informed consent. * Patients may be receiving chemotherapy as long as the agents are not known to cause a peripheral neuropathy. * Patients must have an ECOG Performance Status \< 3 and be able to attend the physician study visits * Patients must not concurrently use gabapentin or pregabalin or must be willing to wean off their anti-convulsant medications prior to starting the trial. * Patients may have diabetes mellitus (type 1 or 2) as long as there is no preexisting neuropathy.
Exclusion criteria
* Patients will not have secondary cause of neuropathic pain including: HIV/AIDS,traumatic injury, or a personal history of non chemotherapy-induced neuropathy. * Patients will not have a history of major depression or severe anxiety. * Women of childbearing age will agree to take measures to prevent pregnancy and will not breast-feed while on the study medication. Women who are currently pregnant will not be invited to participate in this study. * Patients will not have a history of seizures. * Patients cannot be currently receiving antibiotic therapy for tuberculosis (e.g. isoniazid).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Patient-reported Pain Intensity Scores Between the 3 Arms After the Treatment Period Using the Brief Pain Inventory | From the date that the first patient is registered until the last patient completes the 12 weeks of study intervention (approximately 1 year) | Compare patient-reported pain intensity scores after the treatment period (12 weeks) between the 3 arms of the trial. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Individual Patients' Self-reported Overall Pain Relief Scores Before and After the Treatment Period | From the date that the first patient is registered until the last patient completes the 12 weeks of study intervention (approximately 1 year) | Compare individual patients' self-reported pain relief scores before and after the treatment period. |
| Change in Neuropathic Pain Scores in and Between Study Arms Using the Neuropathic Pain Inventory, the FACT-Taxane, and the Leonard Scale. | From the date that the first patient is registered until the last patient completes the 12 weeks of study intervention (approximately 1 year) | Compare changes in neuropathic pain scores within each arm, as well as between the 3 arms of the study. Neuropathic pain will be assessed using 3 tools: the Neuropathic Pain Inventory, the FACT-Taxane, and the Leonard Scale. |
| Differences in Pain Interference Between Study Arms Using the Brief Pain Inventory and the FACT-Taxane | From the date that the first patient is registered until the last patient completes the 12 weeks of study intervention (approximately 1 year) | Compare the pain interference scores after study treatment between study arms using the brief pain inventory and the FACT-Taxane. |
| Change in the Amount of Opioid Medication Used by Patients in Each Arm Before and After Study Treatment | From the date that the first patient is registered until the last patient completes the 12 weeks of study intervention (approximately 1 year) | Record the amount of opioid medication used by patients in each arm before and after the study treatment period. |
Countries
United States
Participant flow
Recruitment details
Opened in 02/2006 (2-arm design with a 4 week treatment period). The 1st patient enrolled in 05/2006; 7 patients enrolled before it was suspended in 04/2007 pending revision (new 3-arm design & 12 week treatment period). Re-opened in 09/2007, but drug manufacturing & funding issues forced it to terminate with no further accrual in 05/2008.
Participants by arm
| Arm | Count |
|---|---|
| All Participants (Original Version) All 7 patients enrolled were during the original version of the study design (2 arms: d-cycloserine 250mg vs. placebo - twice daily for 4 weeks). Since the study went on to change design and then terminate prior to completing accrual, it is not useful to report baseline measures by the original arms/groups. | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Original Version (2 Arms & 4 Weeks) | Never received drug | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | All Participants (Original Version) |
|---|---|
| Age, Customized 40-50 years | 1 participants |
| Age, Customized 51-60 years | 2 participants |
| Age, Customized 61-70 years | 4 participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 3 | 0 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 |
Outcome results
Primary
Difference in Patient-reported Pain Intensity Scores Between the 3 Arms After the Treatment Period Using the Brief Pain Inventory
Compare patient-reported pain intensity scores after the treatment period (12 weeks) between the 3 arms of the trial.
Time frame: From the date that the first patient is registered until the last patient completes the 12 weeks of study intervention (approximately 1 year)
Population: No patients were analyzed for this outcome measure due to a change in study design followed by early termination of the study.
Secondary
Change in Individual Patients' Self-reported Overall Pain Relief Scores Before and After the Treatment Period
Compare individual patients' self-reported pain relief scores before and after the treatment period.
Time frame: From the date that the first patient is registered until the last patient completes the 12 weeks of study intervention (approximately 1 year)
Population: No patients were analyzed for this outcome measure due to a change in study design followed by early termination of the study.
Secondary
Change in Neuropathic Pain Scores in and Between Study Arms Using the Neuropathic Pain Inventory, the FACT-Taxane, and the Leonard Scale.
Compare changes in neuropathic pain scores within each arm, as well as between the 3 arms of the study. Neuropathic pain will be assessed using 3 tools: the Neuropathic Pain Inventory, the FACT-Taxane, and the Leonard Scale.
Time frame: From the date that the first patient is registered until the last patient completes the 12 weeks of study intervention (approximately 1 year)
Population: No patients were analyzed for this outcome measure due to a change in study design followed by early termination of the study.
Secondary
Change in the Amount of Opioid Medication Used by Patients in Each Arm Before and After Study Treatment
Record the amount of opioid medication used by patients in each arm before and after the study treatment period.
Time frame: From the date that the first patient is registered until the last patient completes the 12 weeks of study intervention (approximately 1 year)
Population: No patients were analyzed for this outcome measure due to a change in study design followed by early termination of the study.
Secondary
Differences in Pain Interference Between Study Arms Using the Brief Pain Inventory and the FACT-Taxane
Compare the pain interference scores after study treatment between study arms using the brief pain inventory and the FACT-Taxane.
Time frame: From the date that the first patient is registered until the last patient completes the 12 weeks of study intervention (approximately 1 year)
Population: No patients were analyzed for this outcome measure due to a change in study design followed by early termination of the study.