Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

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Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

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Respiratory Tract Diseases

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Respiratory Tract Neoplasms

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Carcinoma, Bronchogenic

Bronchial Diseases

Antineoplastic Agents

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Gemcitabine

Vinorelbine

Carboplatin

Pemetrexed

Docetaxel

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Antimitotic Agents

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

At discretion of the treating phisician. Common chemotherapic regimens include:

Gemcitabine at 1000 or 1250 mg/m2 IV (in the vein) on day 1 and 8 of each 21 day cycle.

Carboplatin at an AUC of 5 IV on day 1 of each 21 day cycle plus Gemcitabine at 1000 mg/m2 IV on Day 1 and 8 of each 21 day cycle.

Carboplatin at an AUC of 5 IV on Day 1 of each 21 day cycle plus Pemetrexed 500mg/m2 on day 1 IV on Day 1 of each 21 day cycle.

Vinorelbine 30 mg/m2 IV on day 1 and day 8 every 3 of each 21 day cycle.

Number of Cycles: to a maximum of 6 cycles until progression or unacceptable toxicity.

Treatment prescriptions will be based on gene analysis:

* Carboplatin at an AUC of 6 IV (in the vein) on day 1 of each 21 day cycle.
* Gemcitabine at 1000 mg/m2 IV on day 1 and 8 of each 21 day cycle.
* Carboplatin at an AUC of 5 IV on day 1 of each 21 day cycle plus Gemcitabine at 1000 mg/m2 IV on Day 1 of each 21 day cycle.
* Carboplatin at an AUC of 5 IV on Day 1 of each 21 day cycle plus Pemetrexed at 500 mg/m2 IV on Day 1 of each 21 day cycle.
* Pemetrexed 500mg/m2 IV on Day 1 of each 21 day cycle.
* Docetaxel 75 mg/m2 IV on Day 1 of each 21 day cycle. Or Vinorelbine 30 mg/m2 IV on day 1 and day 8 of each 21 day cycle.

Number of Cycles: to a maximum of 6 cycles until progression or unacceptable toxicity.

Silvia Novello, MD,PhD

Marco Angelo Burgio, MD

Alessandra Bearz, MD

Alessandro Gamboni, MD

Gianni Michele Turolla, MD

Maximilian Papi, MD

Silvia Novello, MD, PhD

Domenico Galetta, MD

Giuseppe Banna, MD

Ida Colantonio, MD

Fabiana Cecere, MD

Francesco Grossi, MD

Carlotta Defferrari, MD

Gabriella Farina, MD

Vanesa Gregorc

Paolo Bidoli, MD

Adolfo Favaretto, MD

Lucio Crinò, MD

Claudio Dazzi, MD

Corrado Boni, MD

Francesco Cognetti, MD

oLGA Martelli, MD

Enrico Cortesi, MD

Lorenzo Cordero, MD

Giuseppe Valmadre, MD

Orazio Caffo, MD

Alessandro Follador, MD

Gianpaolo Tortora, MD

Giorgio Vittorio Scagliotti, MD, PhD

Tiziana Vavalà, MD

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).

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.

The EPIC Trial The Elderly Patient Individualized Chemotherapy Trial

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

adverse events and serious adverse events as a measure of safety and tolerability

Rate of successfully conducted gene expression analysis in patients that have signed the informed consent document

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.

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%.

University of Turin, Italy

Principal Investigator

Experimental Arm E.

Patients received treatment according to gene expression strata with four doublet regimens.

Low ERCC1 and Low RRM1 Group - Gemcitabine (G) and Carboplatin (Cb): GCb Group.

Low RRM1 and High ERCC1 Group - Gemcitabine (G) and Docetaxel (D): GD Group.

High RRM1 and Low ERCC1 Group - Docetaxel (D) and Carboplatin (Cb): DCb Group.

High ERCC1 and High RRM1 Group - Vinorelbine (V) and Docetaxel (D): DV Group.

Control Arm C: Gemcitabine and Carboplatin (GCb).

All patients in arm C were treated with GCb regardless of gene expression levels. Patients received up to 6 cycles, and no maintenance therapy was allowed.

GD Group: 40 mg/m\^2 on days 1 and 8, every 21 days

DCb Group: 75 mg/m\^2 on day 1

DV Group: 50 mg/m\^2 on days 1 and 15, every 28 days

GCb Group: Area under the curve (AUC) 5 on day 1, every 21 days

DCb Group: AUC 6 on day 1, every 21 days

Control Arm: Patients received up to 6 cycles, and no maintenance therapy was allowed.

GCb Group: 1,250 mg/m\^2 on days 1 and 8

GD Group: 1,250 mg/m\^2 on days 1 and 8

Control Arm: Patients received up to 6 cycles, and no maintenance therapy was allowed.

Charles Williams, MD

This is a clinical research study to evaluate if chemotherapy in the experimental arm (E) results in a better outcome compared to patients in the standard of care arm (C).

2:1 randomization to experimental arm (E) or standard arm (C). In arm E, treatment of dual-agent chemotherapy will be selected based on RRM1 and ERCC1 expression at the protein level. In arm C, treatment of dual-agent chemotherapy will be gemcitabine/carboplatin, i.e., standard of care.

Before each cycle, blood tests, vital signs, interim medical history, and a physical exam will be performed. Patients will be carefully checked so that immediate intervention can be initiated should an adverse event (i.e. hypersensitivity) occur.

The last treatment cycle according to the study will be cycle #6, or any earlier cycle. Certain tests will be done within 28 days after the last drug infusion. These include physical exam, vital signs, temperature, weight, adverse event evaluation, imaging studies, and blood work.

The study doctor will see the participants every 6 to 8 weeks for at least 12 months after they start treatment. After that, the participants will be followed every 3 months for an additional 24 months.

Phase III of RRM1 & ERCC1 Directed Customized Chemotherapy for the Treatment of Patients With NSCLC

Randomized Phase III Multicenter Trial of RRM1 & ERCC1 Directed Customized Chemotherapy Versus Standard of Care for 1st Line Treatment of Patients With Advanced Non-Small-Cell Lung Cancer

PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. The data of first documented disease progression or death, as defined by Response Evaluation Criteria In Solid Tumors (RECIST), was recorded, and the time interval from randomization to that date was calculated for each patient and used to generate Kaplan-Meier survival estimates and to calculate the PFS at 6 months.

OS at 12 months, determined from the date of randomization. The time interval from randomization to the date of death was calculated for each patient and used to generate Kaplan-Meier survival estimates and to calculate the overall survival.

Number of participants per response category. Response to treatment was determined according to Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
The EPIC Trial The Elderly Patient Individualized Chemotherapy Trial	NCT03402048	Stage IV, NSCLC Lung Neoplasms Bronchial Neopl... Carcinoma, Bron... Lung Diseases Neoplasms Respiratory Tra... Respiratory Tra... Thoracic Neopla...	Carboplatin Gemcitabine Pemetrexed Docetaxel Vinorelbine	70 Years -	University of Turin, Italy
Phase III of RRM1 & ERCC1 Directed Customized Chemotherapy for the Treatment of Patients With NSCLC	NCT00499109	Non-Small Cell ...	Docetaxel Vinorelbine Carboplatin Gemcitabine	18 Years -	H. Lee Moffitt Cancer Center and Research Institute

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