Clinical trial NCT01316744: Ketamine Hydrochloride and Best Pain Management in Treating Cancer Patients With Neuropathic Pain
Official title: A Randomized Double-Blind Controlled Trial of Ketamine Versus Placebo in Conjunction With Best Pain Management in Neuropathic Pain in Cancer Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Cancer
Keywords: long-term effects secondary to cancer therapy in adults
anxiety disorder
depression
pain
unspecified adult solid tumor, protocol specific
neuropathy
accelerated phase chronic myelogenous leukemia
acute undifferentiated leukemia
adult acute lymphoblastic leukemia in remission
adult acute myeloid leukemia in remission
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
atypical chronic myeloid leukemia, BCR-ABL1 negative
blastic phase chronic myelogenous leukemia
chronic myelomonocytic leukemia
chronic phase chronic myelogenous leukemia
mast cell leukemia
meningeal chronic myelogenous leukemia
progressive hairy cell leukemia, initial treatment
prolymphocytic leukemia
recurrent adult acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
recurrent adult T-cell leukemia/lymphoma
refractory chronic lymphocytic leukemia
refractory hairy cell leukemia
relapsing chronic myelogenous leukemia
secondary acute myeloid leukemia
stage I adult T-cell leukemia/lymphoma
stage I chronic lymphocytic leukemia
stage II adult T-cell leukemia/lymphoma
stage II chronic lymphocytic leukemia
stage III adult T-cell leukemia/lymphoma
stage III chronic lymphocytic leukemia
stage IV adult T-cell leukemia/lymphoma
stage IV chronic lymphocytic leukemia
T-cell large granular lymphocyte leukemia
AIDS-related diffuse large cell lymphoma
AIDS-related diffuse mixed cell lymphoma
AIDS-related diffuse small cleaved cell lymphoma
AIDS-related immunoblastic large cell lymphoma
AIDS-related lymphoblastic lymphoma
AIDS-related peripheral/systemic lymphoma
AIDS-related primary CNS lymphoma
AIDS-related small noncleaved cell lymphoma
HIV-associated Hodgkin lymphoma
recurrent adult Hodgkin lymphoma
stage I adult Hodgkin lymphoma
stage II adult Hodgkin lymphoma
stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
cutaneous B-cell non-Hodgkin lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
stage I cutaneous T-cell non-Hodgkin lymphoma
stage II cutaneous T-cell non-Hodgkin lymphoma
stage III cutaneous T-cell non-Hodgkin lymphoma
stage IV cutaneous T-cell non-Hodgkin lymphoma
recurrent mycosis fungoides/Sezary syndrome
stage I mycosis fungoides/Sezary syndrome
stage II mycosis fungoides/Sezary syndrome
stage III mycosis fungoides/Sezary syndrome
stage IV mycosis fungoides/Sezary syndrome
adult grade III lymphomatoid granulomatosis
adult nasal type extranodal NK/T-cell lymphoma
Waldenstrom macroglobulinemia
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
contiguous stage II adult Burkitt lymphoma
contiguous stage II adult diffuse large cell lymphoma
contiguous stage II adult diffuse mixed cell lymphoma
contiguous stage II adult diffuse small cleaved cell lymphoma
contiguous stage II adult immunoblastic large cell lymphoma
contiguous stage II adult lymphoblastic lymphoma
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
contiguous stage II mantle cell lymphoma
contiguous stage II marginal zone lymphoma
contiguous stage II small lymphocytic lymphoma
stage I adult Burkitt lymphoma
stage I adult diffuse large cell lymphoma
stage I adult diffuse mixed cell lymphoma
stage I adult diffuse small cleaved cell lymphoma
stage I adult immunoblastic large cell lymphoma
stage I adult lymphoblastic lymphoma
stage I grade 1 follicular lymphoma
stage I grade 2 follicular lymphoma
stage I grade 3 follicular lymphoma
stage I mantle cell lymphoma
stage I marginal zone lymphoma
stage I small lymphocytic lymphoma
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II mantle cell lymphoma
noncontiguous stage II marginal zone lymphoma
noncontiguous stage II small lymphocytic lymphoma
stage III adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III mantle cell lymphoma
stage III marginal zone lymphoma
stage III small lymphocytic lymphoma
stage IV adult Burkitt lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV mantle cell lymphoma
stage IV marginal zone lymphoma
stage IV small lymphocytic lymphoma
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult grade III lymphomatoid granulomatosis
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
intraocular lymphoma
primary central nervous system non-Hodgkin lymphoma
primary central nervous system Hodgkin lymphoma
post-transplant lymphoproliferative disorder
chronic eosinophilic leukemia
chronic neutrophilic leukemia
primary myelofibrosis
essential thrombocythemia
polycythemia vera
extramedullary plasmacytoma
isolated plasmacytoma of bone
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
primary systemic amyloidosis
refractory multiple myeloma
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
myelodysplastic/myeloproliferative neoplasm, unclassifiable
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2011-03-16
Enrollment: 214
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: SUPPORTIVE_CARE

Brief summary: RATIONALE: Ketamine hydrochloride may lessen neuropathic pain in patients with cancer. It is not yet known whether ketamine hydrochloride given together with the best pain management is more effective than a placebo given together with the best pain management in treating neuropathic pain in patients with cancer.

PURPOSE: This randomized phase III trial is studying ketamine hydrochloride given together with the best pain management to see how well it works compared with giving a placebo together with the best pain management in treating cancer patients with neuropathic pain.

Detailed description: OBJECTIVES:

Primary

* To determine whether ketamine hydrochloride given in addition to best standard pain management improves malignant neuropathic pain compared to best standard pain management alone in patients with cancer.

Secondary

* To compare initial treatment benefit (at day 4 of assessment period of 16 days) using the sensory component of the McGill Short-Form Questionnaire.
* To compare difference in overall pain between the study arms based on the pain-intensity visual-analogue score (VAS).
* To compare difference in neuropathic pain between the study arms based on the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale.
* To assess worst pain score (index neuropathic site) between the two arms.
* To compare patient distress between the two arms based on NCCN Distress Thermometer.
* To assess the side effects and tolerability of trial drug.
* To assess the effect of intervention on quality of life scores (based on Euroqol thermometer), anxiety and depression (based on HADS), and opioid requirements.

OUTLINE: This is a multicenter study.

* Stage 1 (Run-in Period): Opioid doses are optimized, under a defined schedule, for up to a maximum of 10 days to ensure that all patients are on an optimized and stable regimen\* prior to randomization. Following the run-in-period, patients undergo reassessment. Patients who have improved pain scores (i.e., \< 4/10 on the visual-analogue score in the past 24 hours or \< 5 McGill Sensory Scale Score) are taken off the study. Patients whose scores have not improved continue on to Stage 2 of the study.

NOTE: \*Stable regimen is defined as the same dose of controlled release and no more variation than 2 breakthrough opioid doses over the normal for that patient for a period of 48 hours.

* Stage 2 (Titration Period): Patients are randomized to 1 of 2 treatment arms.

  * Arm I: Patients receive oral ketamine hydrochloride 4 times a day. Doses are titrated until when analgesia is achieved or individual side effects appear, for up to 14 days.
  * Arm II: Patients receive an oral placebo 4 times a day. Doses are titrated until when analgesia is achieved or individual side effects appear, for up to 14 days.
* Stage 3 (Assessment Period): Patients receive the trial medication (i.e., ketamine hydrochloride or placebo) at the fixed optimum dose (reached during the titration period) for 16 days.

Patients are allowed to receive breakthrough opioids at any time during the study.

Patients complete quality-of-life and pain-assessment questionnaires periodically. Some patients may undergo blood sample collection periodically for pharmacogenomics studies at a later date.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed cancer
* Index neuropathic pain ≥ 4 on 0-10 (as defined by Leeds Assessment of Neuropathic Symptoms and Signs) that is related to underlying malignancy or resulting from treatment received for this malignancy
* McGill Sensory Scale Score \> 5
* Received a trial of an adjuvant analgesic (gabapentin or amitriptyline or both)

PATIENT CHARACTERISTICS:

* Life expectancy ≥ 2 months
* Fertile patients must use effective contraception
* Able to comply with study procedures
* Diastolic blood pressure ≤ 100 mm Hg at screening
* No seizures in past 2 years
* Not actively hallucinating
* No cerebrovascular disease (strokes)
* No psychotic disorders or cognitive impairment

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* At least 6 weeks since prior and no concurrent chemotherapy or radiotherapy that is likely to affect neuropathic pain
* No change in tumoricidal treatment during the period of the study that is likely to alter pain during the course of the study
* No concurrent class I antiarrhythmic drugs

Primary outcomes:
measure: Time to treatment failure
Secondary outcomes:
measure: Initial treatment benefit (at day 4 of assessment period of 16 days) using the sensory component of the McGill Short-Form Questionnaire
measure: Difference in overall pain between the study arms based on the visual-analogue score
measure: Difference in neuropathic pain between the study arms based on the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale
measure: Worst pain score (index neuropathic site) in the previous 24 hours (between the two arms) at study baseline and then during study assessment period
measure: Patient distress between the two arms based on NCCN Distress Thermometer
measure: Side effects and tolerability of trial drug
measure: Effect of the intervention on quality-of-life scores (based on Euroqol thermometer), anxiety and depression (based on HAD scale), and opioid requirements
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Royal Brompton Hospital
state: England
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre at Western General Hospital
state: Scotland
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
state: Scotland
Study officials:
affiliation: Edinburgh Cancer Centre at Western General Hospital
name: Marie T. Fallon
role: PRINCIPAL_INVESTIGATOR
affiliation: Edinburgh Cancer Centre at Western General Hospital
name: Barry J.A. Laird, MD
role: PRINCIPAL_INVESTIGATOR
References: