Administrative information
Title {1} | Randomized double-blind, placebo-controlled study of oral gabapentin for prevention of neuropathy in patients receiving paclitaxel |
Trial registration {2} | Clinical Trials Registry of India CTRI/2022/02/040030 |
Protocol version {3} | Version 1.1, December 1, 2021 |
Funding {4} | This trial has not received any external funding. Placebo and gabapentin capsules (300 mg) have been provided by Intas pharmaceuticals (Corporate House, Near Sola Bridge, S. G. Highway, Thaltej, Ahmedabad – 380,054) |
Author details {5a} | Praful Pandey1, Akash Kumar1, Deepam Pushpam1, Sachin Khurana1, Prabhat Singh Malik1, Ajay Gogia1, Elavarasi Arunmozhimaran2, Mamta Bhushan Singh2, Dinu Santha Chandran3, and Atul Batra1 1 Department of Medical Oncology, Dr. BR Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India 2 Department of Neurology, All India Institute of Medical Science, New Delhi, India 3 Department of Physiology, All India Institute of Medical Science, New Delhi, India |
Name and contact information for the trial sponsor {5b} | Dr. Atul Batra, Associate Professor, Department of Medical Oncology Dr. BR Ambedkar Institute Rotary Cancer Hospital All India Institute of Medical Sciences, New Delhi, India |
Role of sponsor {5c} | This is an investigator-initiated study, and the sponsor is an academic institute employing the principal investigator. This study will be conducted with logistic, administrative, and other support provided by the institute. |
Introduction
Background and rationale {6a}
Objectives {7}
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To compare the effect of oral gabapentin with placebo in preventing clinically significant peripheral neuropathy (incidence of NCI CTCAEv5.0 grade 2 or higher peripheral neuropathy) in patients with non-metastatic breast, gynecological and lung cancers receiving (neo)adjuvant paclitaxel
Trial design {8}
Methods: participants, interventions, and outcomes
Study setting {9}
Eligibility criteria {10}
Who will take informed consent? {26a}
Additional consent provisions for collection and use of participant data and biological specimens {26b}
Interventions
The explanation for the choice of comparator arm {6b}
Intervention description {11a}
Relevant concomitant care permitted or prohibited during the trial {11d}
Criteria for discontinuing or modifying allocated interventions {11b}
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Permanent discontinuation of paclitaxel by treating physician (unacceptable toxicity or progression of underlying cancer)
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Completion of planned duration or 6 cycles of paclitaxel
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If the investigator determines that continuation of the study treatment is not in the patient’s best interest
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Occurrence of an exclusion criterion affecting patient safety during the conduct of the trial, e.g., pregnancy or psychiatric illness
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Initiation of concomitant treatment that is not permitted
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Failure to comply with the protocol. If a patient consistently fails to attend scheduled assessments in the study, the investigator will determine the reasons and document the circumstances as thoroughly and accurately as possible in the medical records
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The patient declines subsequent treatment or withdraws consent
Strategies to improve adherence to interventions {11c}
Provisions for post-trial care {30}
Outcomes {12}
Grade | Description |
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Grade 1 | Asymptomatic (e.g., loss of deep tendon reflexes) |
Grade 2 | Moderate symptoms; limiting instrumental ADL |
Grade 3 | Severe symptoms; limiting self-care ADL |
Grade 4 | Life-threatening consequences: urgent intervention indicated |
Grade 5 | - |
Outcome | Description |
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Primary outcome | Grade 2 or higher peripheral neuropathy (proportion) |
Secondary | All grades of peripheral neuropathy (proportion) Change in ulnar/median/sural nerve conduction velocity (compared to baseline) and 3 months after therapy cessation (percentage change) Time to develop peripheral neuropathy (days) Patient-reported outcomes using the EORTC QLQ-CIPN20 questionnaire Adherence with oral gabapentin Peripheral neuropathy-related dose changes in paclitaxel Adverse events (NCI CTCAE version 5.0) Autonomic nervous system function (orthostatic fall in systolic blood pressure and heart rate variability with deep breathing) |
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Deep breathing test: The patient will be seated comfortably and will be instructed to undergo 6 cycles of deep breathing (5-s inspiration and 5-s expiration). Variation in pulse rate by the phase of respiration will be documented by counting the number of waveforms on a pulse oximeter and averaging over 6 readings. A change of 15/min or more will be scored as normal, 11–14/min will be scored as borderline, and 10/min or lesser will be scored as abnormal
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Lying to standing test: The patient will rest in a supine position for 10 min during which a baseline blood pressure will be measured. Subsequently, the patient will stand up within 3 s, and repeat blood-pressure recordings shall be taken at 0.5, 1, 2, 2.5, and 5 min, and the maximum fall in systolic blood pressure will be assessed. A fall of 30 mm Hg or more shall be scored as abnormal, 11–29 mm Hg as borderline, and 10 mm Hg or lesser as normal