Development of a Biomarker Directed Strategy to Ameliorate Common Toxicities From Conventional Chemotherapy

Study Overview
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Brief Summary
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Side effects from chemotherapy can be severe in some patients leading to admission to hospital, a worse quality of life and delays in subsequent doses of chemotherapy. A blood test that could predict patients who will go on to develop severe side effects could be useful and might allow early intervention with medicines to reduce the severity of the symptoms and prevent admission to hospital. This study will collect blood samples from patients with lymphoma or sarcoma who are receiving chemotherapy (with an expected admission rate for neutropenic sepsis, one of the side effects that most commonly results in hospital admission, of less than 20%). It will assess whether changes in blood proteins (biomarkers) taken 2 days after the 1st chemotherapy can predict subsequent severe side effects throughout the 4 months of chemotherapy. In addition the investigators will collect data on quality of life and contact with medical professionals to assess the costs of chemotherapy toxicity to both the patient and health service. This will allow us in the future to model the cost effectiveness of using biomarkers in this manner to try and reduce chemotherapy toxicity.

Official Title
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Development of a Biomarker Directed Strategy to Ameliorate Common Toxicities From Conventional Chemotherapy

Conditions
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Lymphoma, Sarcoma

Intervention / Treatment
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* Procedure: Biomarker and health economics


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with lymphoma or sarcoma identified to receive out-patient chemotherapy with an anticipated febrile neutropenia rate of less than 20%. This would include 21 day R-CHOP in patients under 70 and single agent doxorubicin [Aapro et al, 2011a]. Age 18 or older Performance Status 0-2 Before patient registration, written informed consent must be given according to ICH/GCP, and national regulations. Exclusion Criteria: Past history of HIV, Hepatitis B or C positive, due to the difficulties in handling high-risk specimens within CEP. Major surgery, radiotherapy, chemotherapy or mechanism based agents within the last 4 weeks. Radio-immunotherapy within the last 8 weeks. Bilirubin greater than 1.5 X the upper limit of normal and ALT greater than 2.5 x the upper limit of normal (as disturbed liver function tests are associated with elevated CK18) [Gonzalez-Quintela et al, 2009, Lavallard et al, 2011] Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Biomarker and health economics<br>Biomarkers will be taken throughout cycle 1. Health economics will be recorded using a patient side effect diary, a details of admission form, and a patient survey of healthcare use. | Procedure: Biomarker and health economics<br>* Biomarkers CK18 and FLT3 Ligand will be collected<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| sensitivity and specificity of changes in CK18 and FLT 3 ligand at day 3 of chemotherapy to predict subsequent severe toxicity | to confirm in a prospective cohort whether changes in CK18 and FLT3 ligand at day 3 of chemotherapy can identify patients at risk of subsequent severe chemotherapy toxicity | day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of hospital admissions for febrile neutropenia |  | end of chemotherapy at approximately 6 months | 
| Total number of overnight stays or stays in A&E of over 4 hours spent in hospital |  | End of study chemotherapy at approximately 6 months | 
| Dose intensity of chemotherapy achieved compared to planned cumulative dose on initiation of therapy |  | End of chemotherapy at approximately 6 months | 
| Number of total days delay in receiving chemotherapy treatment compared to planned delivery |  | end of chemotherapy at approximately 6 months | 
| Change in QOL at the start of cycles 2, 4 and 6 of chemotherapy and at the end of study as measured by functional assessment of cancer therapy general (FACT-G) and euroqol EQ-5D questionnaires |  | cycle 2 (week6), 4 (week 12), 6 (week 18) and end of study (approximately 6 months) | 
| Total number of contacts (both face to face and telephone) with medical and nursing staff including visits to GP, Accident and Emergency, hospital clinics and telephone consultations with Hotline staff of hospital doctors |  | end of study chemotherapy at approximately 6 months |