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

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.

Study Overview

• Status: Suspended
• Conditions: Sarcoma; Lymphoma
• Intervention / Treatment: Procedure: Biomarker and health economics

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with Lymphoma or sarcoma identified to receive out-patient chemotherapy with an anticipated febrile neutropenia rate of less than 20%.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Biomarker and health economics; 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; Biomarkers CK18 and FLT3 Ligand will be collected

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: The Christie NHS Foundation Trust
• Investigators: Study Chair: Alastair Greystoke, The Christie NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Anticipated): November 1, 2015

Study Registration Dates

• First Submitted: August 9, 2013
• First Submitted That Met QC Criteria: August 12, 2013
• First Posted (Estimate): August 14, 2013

Study Record Updates

• Last Update Posted (Estimate): February 4, 2015
• Last Update Submitted That Met QC Criteria: February 3, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma
• Other Study ID Numbers: 11_DOG05_99