None listed
Conditions
Brief summary
Combination chemotherapy with fluoropyrimidine and oxaliplatin is a commonly used first line chemotherapy regimen, in patients with unresectable metastatic colorectal cancer. Potential oxaliplatin toxicities include chemotherapy induced peripheral neuropathy (CIPN), which can be both acute and chronic and can substantially affect quality of life (QoL). Although acute CIPN is almost always reversible, chronic CIPN can persist following completion of chemotherapy and is frequently irreversible. Chronic CIPN can be reduced, however, by reducing the cumulative dose of oxaliplatin, however currently there is no evidence to guide dose reductions and achieve improved outcome. This study aims to define an acceptable guideline for oxaliplatin dose modification, using patient reported CIPN. Aims and Objectives: The aim of this study is to assess the acceptability of patient reported CIPN in addition to standard care, as a trigger for oxaliplatin dose modification. This could later be compared to standard care alone, in a prospective randomised trial. Primary objective: To determine the acceptability of patient reported CIPN as a trigger for oxaliplatin dose modification, defined as the compliance rate of clinicians with the intervention. Secondary objectives: To determine the interventions effect on: 1. The severity of chronic CIPN 2. Cumulative dose of oxaliplatin 3. Tumour response rate 4. Progression free survival Hypothesis: The addition of patient reported CIPN as a trigger for oxaliplatin dose modification is acceptable and results in reduced severity of chronic CIPN. Study Design and Target Population: A single arm phase 2 acceptability trial, in patients with unresectable metastatic colorectal cancer undergoing palliative XELOX chemotherapy. Intervention: Patients will complete a modified PRO-CTCAE questionnaire prior to each cycle of chemotherapy and this will trigger pre-specified oxaliplatin dose modifications. Outcomes and Measures: Primary outcome: acceptability of the intervention defined by a clinician compliance rate of at least 80%. Secondary outcomes: * Severity of chronic CIPN defined by the percent reduction from baseline EORTC QLQ-CIPN score * Cumulative dose of oxaliplatin at the completion of chemotherapy * Tumour response rate defined by the best response achieved on CT * Progression free survival at 6, 12 and 18 months
Interventions
The intervention involves a questionnaire that is given to patients prior to each cycle of chemotherapy which is given every 3 weeks as an outpatient at secondary hospital settings in the MidCentral Region. Patients will receive up to 8 cycles of chemotherapy.
This questionnaire is a modified version of the NCI PRO-CTCAE neurotoxicity questions. It has been modified for use in this study by also incorporating questions regarding symptom duration and persistence of symptoms. The answers to the qu
The intervention involves a questionnaire that is given to patients prior to each cycle of chemotherapy which is given every 3 weeks as an outpatient at secondary hospital settings in the MidCentral Region. Patients will receive up to 8 cycles of chemotherapy. This questionnaire is a modified version of the NCI PRO-CTCAE neurotoxicity questions. It has been modified for use in this study by also incorporating questions regarding symptom duration and persistence of symptoms. The answers to the questions are then used by the treating clinician who is either the specialist medical oncologist or the training registrar under the supervision of the medical oncologist, to modify the Oxaliplatin dose according to a pre-specified guideline which is outlined in a flow-diagram. This guideline suggests the following modifications: * No numbness or tingling continue with same dose * Reported mild numbness and tingling triggers a 20-25% dose reduction in Oxaliplatin for the subsequent cycle * If a patient reports that mild numbness and tingling occurred on no more than or lasted for no longer than 3 days, the clinician has the option of continuing with the same dose of chemotherapy * If a patient reports persistent mild numbness and tingling present at the time of clinic, this triggers a “hold” on Oxaliplatin and Capecitabine continues. If the numbness or tingling improves or remains mild at the subsequent pre-chemotherapy clinic, Oxaliplatin can be reintroduced with a 20-25% dose reduction * Reported moderate numbness and tingling triggers a “hold” on Oxaliplatin for the subsequent cycle * Capecitabine chemotherapy continues, without Oxaliplatin * Assessment of numbness and tingling at the subsequent pre-chemotherapy clinic * If numbness and tingling is present and has not improved, Oxaliplatin is discontinued * If numbness and tingling has resolved or has improved and is reported as mild on the modified PRO-CTCAE questionnaire, Oxaliplatin can be reintroduced with a 20-25% dose reduction * Reported severe or very severe numbness and tingling triggers discontinuation of Oxaliplatin * Dose reductions for numbness and tingling can be made on two occasions. If there is ongoing numbness and tingling after 2 dose reductions, Oxaliplatin is discontinued The questionnaire is given to the patient when they come for their pre-chemotherapy clinic and Oxaliplatin modifications made for their subsequent cycle. At each clinic, the clinician will fill out a form, reporting whether the intervention has been followed and if it hasn't, the reason for this.
Sponsors
MidCentral Regional Cancer Treatment Services
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Prevention
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients with histologically proven colorectal adenocarcinoma * Histological confirmation of metastatic disease or of the primary lesion where an alternative cause for metastatic disease is considered unlikely 2. Unresectable metastatic disease with radiological measurable disease according to RECIST v1.1 on computed tomography (CT) 3. Assessed as suitable for palliative XELOX chemotherapy 4. No contraindications to capecitabine or oxaliplatin chemotherapy 5. Able to complete questionnaires and comply with intervention, assessments and follow-up 6. Written, informed consent
Exclusion criteria
1. Age < 18 years 2. Patients with a pre-existing neurological condition including established diabetic peripheral neuropathy 3. Patients who have previously been treated with neurotoxic chemotherapy agents including platinums, taxanes and vinka-alkaloids 4. Patients with contra-indications to capecitabine or oxaliplatin
Outcome results
None listed