Clinical trial NCT03402048: The EPIC Trial The Elderly Patient Individualized Chemotherapy Trial
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Stage IV, NSCLC
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Keywords: Lung Cancer
Elderly
First line
Customized chemotherapy
Pharmacogenomic-driven
NSCLC
Lead sponsor: University of Turin, Italy
Sponsor class: OTHER
First posted: 2018-01-17
Enrollment: 567
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Survival
timeFrame: from the date of randomization
Secondary outcomes:
measure: Progression Free survival
timeFrame: at six months determined from the date of randomization
Other outcomes:
measure: AE and SAE (according to CTCAE version 4.0)
timeFrame: every week from the day 1 treatment until the end of treatment (up to 18 weeks)
measure: Rate of successfully conducted gene expression analysis in patients that have signed the informed consent document
timeFrame: up to10 business days of submission of the tumor specimen
Locations:
city: Meldola
country: Italy
facility: IRCSSIstituto Scientifico Romagnolo per lo studio e la cura dei tumori IRST
state: Forlì
city: Aviano
country: Italy
facility: Istituto Nazionale Tumori
state: Pordenone
city: Faenza
country: Italy
facility: Ospedale di Faenza
state: Ravenna
city: Lugo
country: Italy
facility: Ospedale di Lugo
state: Ravenna
city: Cattolica
country: Italy
facility: AUSL Rimini-Oncologia Medica Cattolica
state: Rimini
city: Orbassano
country: Italy
facility: AOU San Luigi Gonzaga, Department of Oncology, University of Turin
state: Turin
city: Bari
country: Italy
facility: Ospedale Giovanni Paolo II
city: Catania
country: Italy
facility: AO Cannizzaro
city: Cuneo
country: Italy
facility: AOU Santa Croce e Carle
city: Firenze
country: Italy
facility: Azienda Ospedaliera Careggi
city: Genova
country: Italy
facility: Istituto Nazionale per la Ricerca sul Cancro
city: Genova
country: Italy
facility: Ospedale Galliera
city: Milano
country: Italy
facility: Azienda Ospedaliera Fatebenefratelli
city: Milano
country: Italy
facility: Ospedale S. Raffaele
city: Monza
country: Italy
facility: AO San Gerardo
city: Padova
country: Italy
facility: Istituto Oncologico Veneto
city: Perugia
country: Italy
facility: Ospedale Santa MAria della Misericordia
city: Ravenna
country: Italy
facility: Ospedale S MAria delle Croci
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova
city: Rimini
country: Italy
facility: AUSL Rimini-Oncologia medica
city: Roma
country: Italy
facility: Istituto Nazionale Tumori Regina Elena
city: Roma
country: Italy
facility: Ospedale S. Giovanni Addolorata
city: Roma
country: Italy
facility: Policlinico Umberto I- Università la Sapienza
city: Sassari
country: Italy
facility: AOU Sassari
city: Sondalo
country: Italy
facility: Azienda Ospedaliera Sondalo
city: Trento
country: Italy
facility: Ospedale Santa Chiara
city: Udine
country: Italy
facility: AOU S.M. Misericordia
city: Verona
country: Italy
facility: AOU Verona
Study officials:
affiliation: University of Turin, Italy
name: Silvia Novello, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Univerisity of Turin
name: Giorgio Vittorio Scagliotti, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Turin, Italy
name: Tiziana Vavalà, MD
role: PRINCIPAL_INVESTIGATOR
References: