Behaviors and Mental Disorders

All Conditions

Quality of Life

Patricia TRESCA, MD

Xavier PAOLETTI, PhD

A prospective cohort of 250 patients with solid tumours included in phase I clinical trials of targeted agents will be enrolled. Patients will be treated with MTA in mono therapy or in association with chemotherapy or other targeted agents in 4 large phase I centers.

Patients from trials investigating chemotherapy alone will not be included. Quality of life will be assessed during the treatment period.

The main objective of phase I dose finding studies is to identify the recommended phase II dose. The primary endpoint is the dose limiting toxicity (DLT) which is generally measured using the NCI common toxicity criteria (NCI-CTCAE) graded scale. This scale, developed for the investigation of cytotoxic chemotherapy administered in a limited number of cycles including rest period, is well adapted to identify the drug effect on organ dysfunction and life threatening events. However it may be less relevant to reflect the patient's feeling regarding the tolerability of the treatment under study resulting in over or under estimation of these toxicities.

Moreover, targeted therapies and more specifically the ones administered orally are given over long periods often with continuous schedules. Moderate toxic side effects lasting over a long period are usually not considered as DLT. The health related quality of life of patients as well as other patient reported outcome including symptom scale in addition to usual NCI CTCAE scale could be a relevant variable to detect intolerable treatments. It has not been studied prospectively to date in phase I trials.

A prospective cohort of 250 patients with solid tumours included in phase I clinical trials of targeted agents will be enrolled. Patients will be treated with MTA in mono therapy or in association with chemotherapy or other targeted agents in 4 large phase I centers.

Patients from trials investigating chemotherapy alone will not be included.

Patients included in a phase I trial will be requested to fill in

* a questionnaire of health related quality of life (the EORTC PAL 15 questionnaire)
* a questionnaire of symptoms (MDASI)
* a questionnaire on symptoms specific of MTA at baseline and at each cycle of treatment and 6 weeks after the end of treatment.

The sponsor of the therapeutic phase I trials will be informed that the present research is running and that it will not interfere with their investigational protocol. Each phase I center has the latitude to propose or not the health-related quality of life research to patients included in a given phase I trial.

Prospective Observational Study to Investigate the Added Value of the Health Related Quality of Life and Patient Reported Symptoms in the Identification of the Recommended Phase II Dose in Phase I Trials of Molecularly Targeted Therapies.

To evaluate whether some toxic side events that are non dose limiting according to the phase I protocol are reported as intolerable by the patients using either specific HR QoL questionnaires or patient reported scales of symptoms

Identify if some dimensions of the quality of life affected by the treatment are not captured by the EORTC PAL 15 questionaries.

Interviews will be realized on a sub sample of patients. An explorative qualitative research could evaluate patients' experience of the impact, burden, tolerability or acceptability of phase I anti-cancer drug trials addressing patients' perception of symptoms, functioning and overall quality of life. Interviews results contrasted with the PAL15 questionnaires will enable to determine whether a QoL questionnaire dedicated to phase I trials is necessary and what are the main components felt essential to the patients.

Centre Georges Francois Leclerc

Institut Curie

All Drugs and Chemicals

Immunomodulating Agents

Chemotherapy, ITK, Hormotherapy, Immunotherapy

Phase I

Antoine Italiano, MD-PhD

Overview of response rate published in recent oncology phase I trials

Critics have raised a fundamental ethical challenge about phase 1 cancer research. They point to an expected paucity of benefits, since approximately 5% of patients in phase 1 trials are reported to have tumor shrinkage.

Objective was to conduct a search of the literature using PubMed to identify articles about phase 1 trials that were published from January 1, 2014, through June 30, 2015. The primary end point was the response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

Clinically relevant trials' characteristics were investigated as candidate factors associated with the RR: Funding source (Academic / Industrial), First-in man trial (Yes / No), Expansion cohort (Yes / No), Number of targeted organs (Single / Multiple), Therapy (Single / Combination), Treatment (MAB-Immuno / ITK / Chimioth-HT-other), Biological eligibility criterion (Yes / No), as well as the number of assessable patients, which for ease of clinical interpretation was transformed into a qualitative variable (0-25 / 26 - 50 / 51+).

The RR was described according to the individual trials' characteristics. Associations with trials's characteristics were investigated using statistical modeling.

Trends in Modern Phase 1 Oncology Trials

Number of reported responses (complete \[CR\] and partial \[PR\]) divided by the number of reported assessable patients

Institut Bergonié

All-Cause Mortality, Serious, and Other (Not Including Serious) Adverse Events were not monitored/assessed

Participants included in Phase 1 Oncology Trials, published from January 1, 2014, through June 30, 2015.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prospective Observational Study to Investigate the Added Value of the Health Related Quality of Life and Patient Reported Symptoms in the Identification of the Recommended Phase II Dose in Phase I Trials of Molecularly Targeted Therapies.	NCT02857699	Solid Tumors Quality of Life		-	Institut Curie
Trends in Modern Phase 1 Oncology Trials	NCT03676270	Cancer	Phase I	18 Years -	Institut Bergonié
Trends in Modern Phase 1 Oncology Trials	NCT03676270	Cancer	Phase I	18 Years -	Institut Bergonié
Prospective Observational Study to Investigate the Added Value of the Health Related Quality of Life and Patient Reported Symptoms in the Identification of the Recommended Phase II Dose in Phase I Trials of Molecularly Targeted Therapies.	NCT02857699	Solid Tumors Quality of Life		-	Institut Curie

Spots Global Cancer Trial Database for phase i trials