NCT03402048

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).

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
567

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Jul 2012

Longer than P75 for phase_3

Geographic Reach
1 country

28 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2012

Completed
2.4 years until next milestone

First Submitted

Initial submission to the registry

November 17, 2014

Completed
3.2 years until next milestone

First Posted

Study publicly available on registry

January 17, 2018

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2020

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2021

Completed
Last Updated

November 4, 2020

Status Verified

November 1, 2020

Enrollment Period

8.4 years

First QC Date

November 17, 2014

Last Update Submit

November 3, 2020

Conditions

Keywords

Lung CancerElderlyFirst lineCustomized chemotherapyPharmacogenomic-drivenNSCLC

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (1)

  • Progression Free survival

    at six months determined from the date of randomization

Other Outcomes (2)

  • AE and SAE (according to CTCAE version 4.0)

    every week from the day 1 treatment until the end of treatment (up to 18 weeks)

  • 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

Study Arms (2)

control arm

ACTIVE COMPARATOR

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.

Drug: CarboplatinDrug: GemcitabineDrug: PemetrexedDrug: DocetaxelDrug: Vinorelbine

experimental arm

EXPERIMENTAL

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.

Drug: CarboplatinDrug: GemcitabineDrug: PemetrexedDrug: DocetaxelDrug: Vinorelbine

Interventions

control armexperimental arm
Also known as: Gemzar
control armexperimental arm
Also known as: Alimta
control armexperimental arm
Also known as: Taxotere
control armexperimental arm
Also known as: Navelbine
control armexperimental arm

Eligibility Criteria

Age70 Years+
Sexall
Healthy VolunteersNo
Age GroupsOlder Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (28)

IRCSSIstituto Scientifico Romagnolo per lo studio e la cura dei tumori IRST

Meldola, Forlì, Italy

RECRUITING

Istituto Nazionale Tumori

Aviano, Pordenone, Italy

RECRUITING

Ospedale di Faenza

Faenza, Ravenna, Italy

RECRUITING

Ospedale di Lugo

Lugo, Ravenna, Italy

RECRUITING

AUSL Rimini-Oncologia Medica Cattolica

Cattolica, Rimini, Italy

RECRUITING

AOU San Luigi Gonzaga, Department of Oncology, University of Turin

Orbassano, Turin, 10043, Italy

RECRUITING

Ospedale Giovanni Paolo II

Bari, Italy

RECRUITING

AO Cannizzaro

Catania, Italy

RECRUITING

AOU Santa Croce e Carle

Cuneo, Italy

RECRUITING

Azienda Ospedaliera Careggi

Florence, Italy

RECRUITING

Istituto Nazionale per la Ricerca sul Cancro

Genova, Italy

RECRUITING

Ospedale Galliera

Genova, Italy

RECRUITING

Azienda Ospedaliera Fatebenefratelli

Milan, Italy

RECRUITING

Ospedale S. Raffaele

Milan, Italy

RECRUITING

AO San Gerardo

Monza, Italy

RECRUITING

Istituto Oncologico Veneto

Padua, Italy

RECRUITING

Ospedale Santa MAria della Misericordia

Perugia, Italy

RECRUITING

Ospedale S MAria delle Croci

Ravenna, Italy

RECRUITING

Arcispedale Santa Maria Nuova

Reggio Emilia, Italy

RECRUITING

AUSL Rimini-Oncologia medica

Rimini, Italy

RECRUITING

Istituto Nazionale Tumori Regina Elena

Roma, Italy

RECRUITING

Ospedale S. Giovanni Addolorata

Roma, Italy

RECRUITING

Policlinico Umberto I- Università la Sapienza

Roma, Italy

RECRUITING

AOU Sassari

Sassari, Italy

RECRUITING

Azienda Ospedaliera Sondalo

Sondalo, Italy

RECRUITING

Ospedale Santa Chiara

Trento, Italy

RECRUITING

AOU S.M. Misericordia

Udine, Italy

RECRUITING

AOU Verona

Verona, Italy

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell LungLung NeoplasmsBronchial NeoplasmsCarcinoma, BronchogenicLung DiseasesNeoplasmsRespiratory Tract DiseasesRespiratory Tract NeoplasmsThoracic Neoplasms

Interventions

CarboplatinGemcitabinePemetrexedDocetaxelVinorelbine

Condition Hierarchy (Ancestors)

Neoplasms by SiteBronchial Diseases

Intervention Hierarchy (Ancestors)

Coordination ComplexesOrganic ChemicalsHeterocyclic CompoundsDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingGuanineHypoxanthinesPurinonesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingGlutamatesAmino Acids, AcidicAmino AcidsAmino Acids, Peptides, and ProteinsAmino Acids, DicarboxylicTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsDiterpenesTerpenesVinca AlkaloidsSecologanin Tryptamine AlkaloidsIndole AlkaloidsAlkaloidsIndolesIndolizidinesIndolizines

Study Officials

  • Silvia Novello, MD, PhD

    University of Turin, Italy

    PRINCIPAL INVESTIGATOR
  • Giorgio Vittorio Scagliotti, MD, PhD

    Univerisity of Turin

    PRINCIPAL INVESTIGATOR
  • Tiziana Vavalà, MD

    University of Turin, Italy

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Silvia Novello, MD,PhD

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

November 17, 2014

First Posted

January 17, 2018

Study Start

July 1, 2012

Primary Completion

December 1, 2020

Study Completion

May 1, 2021

Last Updated

November 4, 2020

Record last verified: 2020-11

Locations