The EPIC Trial The Elderly Patient Individualized Chemotherapy Trial

Neoplasms Clinical Trial

— EPIC  

Official title:

Randomized Phase III Multicenter Trial of Customized Chemotherapy Versus Standard of Care for1st Line Treatment of Elderly Patients With Advanced Non-Small-Cell Lung Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03402048
• Other study ID #: 2012-001194-81
• Status: Recruiting
• Phase: Phase 3
• Start date: July 2012
• Est. completion date: May 2021

Study information

• Verified date: November 2020
• Source: University of Turin, Italy
• Contact: Silvia Novello, MD,PhD
• Phone: +390119026978
• Email: silvia.novello[@]unito.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized phase III trial that will randomize elderly patients(70 years of age and older) who are not considered eligible for standard doublet or triplet regimens. In a 2:1 fashion, patients will be randomized to the customization arm or the standard arm, respectively. This trial will be offered to patients who are previously untreated for stage IV NSCLC.

The primary objective is to evaluate if chemotherapy selection based on histology and tumoral molecular determinants ERCC1, RRM1 and TS (arm A, the experimental arm) results in superior outcome in elderly patients with untreated, advanced NSCLC compared to standard of care treatments (arm B, the standard arm).

Description:

The study population will consist of patients with histologically or cytologically proven stage IV NSCLC, who have not been previously treated with chemotherapy for stage IV and are either elderly (70 years of age and older). Patients must fulfill all the inclusion/exclusion criteria to be eligible.

Tissue will be obtained, and gene expression analysis will be performed at the University of Turin. The tissue sample used for this analysis will be obtained from the biopsy procedure performed as standard of care procedures during the patient's diagnosis and staging. Patients will be randomized to either Arm A: Experimental or Arm B: Standard of Care in a 2:1 fashion.

Tissue will be obtained for gene analysis for ALL patients. However, ONLY patients randomized to Arm A will receive the genetic analysis results. Genetic results will not be disclosed to the registering center for those patients randomized to Arm B: Standard of Care.

For patients randomized to Arm A: Experimental arm, the chemotherapy treatment prescription will be based on the gene analysis according to the protocol. For patients randomized to Arm B: Standard of Care arm, the chemotherapy treatment will be at the discretion of the care provider.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 567
• Est. completion date: May 2021
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years and older

Eligibility

Inclusion Criteria:

Histologically or cytologically confirmed NSCLC.

• Stage IV NSCLC by the AJCC Staging Manual 7th edition (2010).

• Measurable or evaluable disease by RECIST 1.1.

• Age equal or more than 70 years.

• Performance Status 0 or 1 (by ECOG criteria).

• Adequate bone marrow function.

• Signed informed consent document (ICD).

• Men with partners in the childbearing age group must use effective contraception.

• Previous surgery for NSCLC (more than 30 days before study registration) is allowed.

• Previous radiotherapy is allowed if: the time between completion of RT and initiation of study treatment is at least 7 days,the patient has fully recovered from all toxic effects, and at least one target lesion or evaluable disease is outside the radiation field.

• Previous chemotherapy is allowed if the last dose was administered equal to or greater than 12 months ago. This chemotherapy must have been given in an adjuvant or neoadjuvant mode prior to or after a curative intent surgical resection for a NSCLC. Patient should be previously untreated for metastatic disease.

• Patients with stable brain metastases will be allowed to enroll. Stable brain metastasis is defined as no progression of brain metastases 14 days after conclusion of definitive treatment as documented by a CT scan or MRI of the brain.

Exclusion Criteria:

• Prior systemic chemotherapy or immunotherapy for advanced NSCLC.

• Prior malignancies, except: cured non-melanoma skin cancer, curatively treated in situ carcinoma of the cervix, or any other curatively treated malignancy with no evidence of disease recurrence for at least 2 years.

• Presence of uncontrolled brain or leptomeningeal metastases.

• Peripheral neuropathy or hearing loss of neural origin equal to or greater than grade 2 by CTCAE v 4.0 except if due to trauma.

• Other serious illness or medical condition, including but not limited to: congestive heart failure;myocardial infarction within 6 months;significant neurologic or psychiatric disorders that would impact study participation as judged by the treating physician; infection requiring I.V. antibiotics; tuberculosis with ongoing therapy at study entry, superior vena cava syndrome, except if controlled with radiation, active peptic ulcer disease; unstable diabetes mellitus;any contraindication to high dose corticosteroid therapy such as herpes simplex, herpes zoster, hepatitis, or other disease.

• Hypercalcemia requiring therapeutic intervention.

• Clinically significant ascites and/or pericardial effusion.

• Patients with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80.

• Concurrent treatment with other investigational drugs.

• Patients known to harbor sensitizing EGFR mutations in exons 18, 19 and 21. Patients with resistance mutation in exon 20 will be allowed to enroll i.e. T790M and D770. The rare patient who has both a resistance mutation and a sensitizing mutation at the diagnoses will be excluded in the protocol.

• Patients whose tissue submission is not of adequate size to perform molecular testing will be excluded.

• Patients known to have translocations of ALK will also be excluded; however, testing for ALK translocation prior to study entry is not mandated.

Related Conditions & MeSH terms

• Bronchial Neoplasms
• Carcinoma, Bronchogenic
• Lung Diseases
• Lung Neoplasms
• Neoplasms
• Respiratory Tract Diseases
• Respiratory Tract Neoplasms
• Stage IV, NSCLC
• Thoracic Neoplasms

Intervention

Drug:
• Carboplatin

• Gemcitabine

• Pemetrexed

• Docetaxel

• Vinorelbine

Locations

Country	Name	City	State
Italy	Istituto Nazionale Tumori	Aviano	Pordenone
Italy	Ospedale Giovanni Paolo II	Bari
Italy	AO Cannizzaro	Catania
Italy	AUSL Rimini-Oncologia Medica Cattolica	Cattolica	Rimini
Italy	AOU Santa Croce e Carle	Cuneo
Italy	Ospedale di Faenza	Faenza	Ravenna
Italy	Azienda Ospedaliera Careggi	Firenze
Italy	Istituto Nazionale per la Ricerca sul Cancro	Genova
Italy	Ospedale Galliera	Genova
Italy	Ospedale di Lugo	Lugo	Ravenna
Italy	IRCSSIstituto Scientifico Romagnolo per lo studio e la cura dei tumori IRST	Meldola	Forlì
Italy	Azienda Ospedaliera Fatebenefratelli	Milano
Italy	Ospedale S. Raffaele	Milano
Italy	AO San Gerardo	Monza
Italy	AOU San Luigi Gonzaga, Department of Oncology, University of Turin	Orbassano	Turin
Italy	Istituto Oncologico Veneto	Padova
Italy	Ospedale Santa MAria della Misericordia	Perugia
Italy	Ospedale S MAria delle Croci	Ravenna
Italy	Arcispedale Santa Maria Nuova	Reggio Emilia
Italy	AUSL Rimini-Oncologia medica	Rimini
Italy	Istituto Nazionale Tumori Regina Elena	Roma
Italy	Ospedale S. Giovanni Addolorata	Roma
Italy	Policlinico Umberto I- Università la Sapienza	Roma
Italy	AOU Sassari	Sassari
Italy	Azienda Ospedaliera Sondalo	Sondalo
Italy	Ospedale Santa Chiara	Trento
Italy	AOU S.M. Misericordia	Udine
Italy	AOU Verona	Verona

Sponsors (1)

Lead Sponsor	Collaborator
University of Turin, Italy

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	AE and SAE (according to CTCAE version 4.0)	adverse events and serious adverse events as a measure of safety and tolerability	every week from the day 1 treatment until the end of treatment (up to 18 weeks)
Other	Rate of successfully conducted gene expression analysis in patients that have signed the informed consent document	Rate of successfully conducted gene expression analysis in patients that have signed the informed consent document	up to10 business days of submission of the tumor specimen
Primary	Overall Survival	primary endpoint is OS (determined from the date of randomization).Assuming an exponential survival distribution for both treatment arms and a median survival time of 8 months in the control arm we anticipate to detect an improvement of three months in OS.	from the date of randomization
Secondary	Progression Free survival	PFS at 6 months (determined from the date of randomization). The anticipated 6-month PFS in arm B is approximately 25% and the goal in the experimental arm is to achieve a 32% improvement to 33%.	at six months determined from the date of randomization