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GEfitinib Plus viNOrelbine in Advanced EGFR Mutated NSCLC. GENOA Trial

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02319577
Recruitment Status : Unknown
Verified December 2014 by Francesco Grossi, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Recruitment status was:  Recruiting
First Posted : December 18, 2014
Last Update Posted : December 18, 2014
Sponsor:
Information provided by (Responsible Party):
Francesco Grossi, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

Study Description
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Brief Summary:
A sub-population of patients affected by non-small cell lung cancer (NSCLC) with activating mutations of the epidermal growth factor receptor (EGFR) do not gain benefit from treatment with tyrosine-kinase inhibitors (TKIs). The hypothesis of this study is that the addition of chemotherapy with oral vinorelbine to first-line TKI might result in improved outcomes in EGFR-mutated patients.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Drug: oral vinorelbine Drug: Gefitinib Phase 2

Detailed Description:

In spite of the dramatic improvements obtained with EGFR-TKIs in patients affected by NSCLC with activating mutations of EGFR, a fraction of these patients (about 30%) do not respond to EGFR-TKIs or achieve a response of short duration. It has been suggested that these patients may be affected by additional mutations that confer resistance to EGFR-TKIs in spite of the presence of activating mutations of the EGFR gene. Pre-clinical studies show that the addition of chemotherapy to gefitinib may result in increased anti-proliferative activity, and subsequent clinical studies suggest that the synergic activity of gefitinib and chemotherapy can depend from the employed schedules (concurrent versus sequential). Additionally, data from phase I trials of gefitinib plus vinorelbine revealed a high incidence of severe hematological toxicity with concurrent administration, while sequential schedules resulted in a more manageable safety profile.

On the basis of the aforementioned data, we hypothesize that the sequential combination of vinorelbine and gefitinib might result in improved outcomes (in terms of response and survival) in EGFR-mutated NSCLC over gefitinib alone with acceptable tolerability. The availability of an oral formulation of vinorelbine makes it possible to offer the patients an exclusively oral treatment.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized, Phase II Study With Gefitinib Plus Vinorelbine Versus Gefitinib Alone in Patients Affected by Non-small Cell Lung Cancer (NSCLC) With Activating Mutations of EGFR
Study Start Date : March 2012
Estimated Primary Completion Date : June 2015
Estimated Study Completion Date : December 2015

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Gefitinib plus oral vinorelbine

Arm A (21-days cycles until progressive disease or unacceptable toxicity):

Oral vinorelbine 60 mg/mq on days 1,8 Gefitinib 250 mg daily from day 9 to day 21

 Drug: oral vinorelbine
Anti-neoplastic drug (PO chemotherapeutical agent, vinka alkaloid)
Other Name: Navelbine

Drug: Gefitinib
EGFR tyrosine kinase inhibitor
Other Name: Iressa
Active Comparator: Gefitinib alone

Arm B (21-days cycles until progressive disease or unacceptable toxicity):

Gefitinib 250 mg daily from day 1 to day 21

 Drug: Gefitinib
EGFR tyrosine kinase inhibitor
Other Name: Iressa


Outcome Measures
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Primary Outcome Measures :
  1. Progression-free survival (PFS) rate at 6 months [ Time Frame: 6 months; tumor assessment is performed every 6 weeks from randomization until progressive disease ]
    Progression-free survival is defined as the time from randomization until disease progression or death due to any cause.


Secondary Outcome Measures :
  1. Overall survival (OS) rate at 1 year (1Y-OS), 2 years (2Y-OS), and 3 years (3Y-OS) [ Time Frame: Overall survival assessment is performed at every visit from randomization of each patient until his/her death ]
    Overall survival is defined as the time from randomization to the date of patient date due to any cause or discontinuation of the study. Each OS rate is calculated at the respective end-point (1 year for 1Y-OS, 2 years for 2Y-OS, and 3 years for 3Y-OS).

  2. Response rate (RR) [ Time Frame: tumor assessment is performed every 6 weeks from the start of study treatment until progressive disease ]
    Assessment is performed by response evaluation criteria in solid tumors (RECIST) version 1.1

  3. Safety profile: Safety will be assessed by medical interview, physical examination, and blood collection for complete blood count on days 1 and 8 and biochemistry [ Time Frame: assessment of safety profile is performed at every visit (on day 1 and day 8 of each 21-days cycle) from the start of study treatment until three weeks after its interruption due to intolerance or progressive disease ]
    Evaluation of the safety profile of gefitinib plus oral vinorelbine as compared to the safety profile of gefitinib alone. Safety will be assessed by medical interview, physical examination, and blood collection for complete blood count on days 1 and 8 and biochemistry (sodium, chloride, potassium, calcium, magnesium, phosphorus, glucose, ammonia, creatinine, alkaline phosphatase, aspartate transaminase, alanine transaminase, γ-glutamyl transpeptidase, lactate dehydrogenase, total and fractioned bilirubin, total proteins, albumin) on day 1.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent
  • At least 18 years old
  • Histologically confirmed NSCLC
  • Stage IV disease
  • Evidence of activating mutations of EGFR
  • Measurable disease (assessed by RECIST 1.1)
  • No previous chemotherapy or biological therapy for NSCLC
  • Previous radiation treatment is allowed, unless all the eligible target lesions have been irradiated, and provided that at least 2 weeks have passed from the end of radiation therapy to the start of the treatment in the study
  • Eastern Cooperative Oncology Group (ECOG) performance status : 0-1
  • Adequate baseline bone marrow, hepatic and renal function
  • In presence of central nervous system metastases, the patient has to be asymptomatic for at least 4 weeks before starting treatment in the study
  • Patients who had received neoadjuvant or adjuvant chemotherapy, or concurrent chemo-radiation for non-metastatic, radically treated NSCLC are considered eligible, provided that they had not received vinorelbine as part of such treatment
  • Female patients must provide a negative pregnancy test (serum or urine) prior to treatment

Exclusion Criteria:

  • Other malignancies within the last 3 years, with exclusion of non-melanoma skin neoplasms and in-situ carcinoma of the cervix
  • Grade III-IV New York Heart Association (HYHA) cardiac dysfunction
  • Acute myocardial infarction or pulmonary embolism in the last 6 months
  • Brain metastases or meningeal carcinomatosis or spinal cord compression, unless controlled and asymptomatic for at least 30 days before starting study treatment
  • HIV positivity or AIDS requiring pharmacological treatment
  • Pregnancy or lactation
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02319577


Contacts
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Contact: Francesco Grossi, MD +39 010 5600385 francesco.grossi@hsanmartino.it

Locations
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Italy
IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro Recruiting
Genova, Italy, 16132
Contact: Francesco Grossi, MD    +39 010 5600385    francesco.grossi@hsanmartino.it   
Sponsors and Collaborators
IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Investigators
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Principal Investigator: Francesco Grossi, MD IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro
More Information
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Responsible Party: Francesco Grossi, MD, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
ClinicalTrials.gov Identifier: NCT02319577    
Other Study ID Numbers: Genoa trial
First Posted: December 18, 2014    Key Record Dates
Last Update Posted: December 18, 2014
Last Verified: December 2014
Keywords provided by Francesco Grossi, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy:
NSCLC
EGFR
vinorelbine
gefitinib
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Bronchial Neoplasms
Respiratory Tract Diseases
Carcinoma, Bronchogenic
 Vinorelbine
Gefitinib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors