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GEfitinib Plus viNOrelbine in Advanced EGFR Mutated NSCLC. GENOA Trial

Primary Purpose

Non Small Cell Lung Cancer

Status

Unknown status

Phase

Phase 2

Locations

Italy

Study Type

Interventional

Intervention

oral vinorelbine

Gefitinib

About this trial

This is an interventional treatment trial for Non Small Cell Lung Cancer focused on measuring NSCLC, EGFR, vinorelbine, gefitinib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul CancroRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Gefitinib plus oral vinorelbine

Gefitinib alone

Arm Description

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

Arm B (21-days cycles until progressive disease or unacceptable toxicity): Gefitinib 250 mg daily from day 1 to day 21

Outcomes

Primary Outcome Measures

Progression-free survival (PFS) rate at 6 months

Progression-free survival is defined as the time from randomization until disease progression or death due to any cause.

Secondary Outcome Measures

Overall survival (OS) rate at 1 year (1Y-OS), 2 years (2Y-OS), and 3 years (3Y-OS)

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).

Response rate (RR)

Assessment is performed by response evaluation criteria in solid tumors (RECIST) version 1.1

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

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.

Full Information

NCT ID

NCT02319577

First Posted

December 9, 2014

Last Updated

December 17, 2014

Sponsor

IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

1. Study Identification

Unique Protocol Identification Number

NCT02319577

Brief Title

GEfitinib Plus viNOrelbine in Advanced EGFR Mutated NSCLC. GENOA Trial

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 Type

Interventional

2. Study Status

Record Verification Date

December 2014

Overall Recruitment Status

Unknown status

Study Start Date

March 2012 (undefined)

Primary Completion Date

June 2015 (Anticipated)

Study Completion Date

December 2015 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

4. Oversight

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non Small Cell Lung Cancer

Keywords

NSCLC, EGFR, vinorelbine, gefitinib

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Gefitinib plus oral vinorelbine

Arm Type

Experimental

Arm Description

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

Arm Title

Gefitinib alone

Arm Type

Active Comparator

Arm Description

Arm B (21-days cycles until progressive disease or unacceptable toxicity): Gefitinib 250 mg daily from day 1 to day 21

Intervention Type

Drug

Intervention Name(s)

oral vinorelbine

Other Intervention Name(s)

Navelbine

Intervention Description

Anti-neoplastic drug (PO chemotherapeutical agent, vinka alkaloid)

Intervention Type

Drug

Intervention Name(s)

Gefitinib

Other Intervention Name(s)

Iressa

Intervention Description

EGFR tyrosine kinase inhibitor

Primary Outcome Measure Information:

Title

Progression-free survival (PFS) rate at 6 months

Description

Progression-free survival is defined as the time from randomization until disease progression or death due to any cause.

Time Frame

6 months; tumor assessment is performed every 6 weeks from randomization until progressive disease

Secondary Outcome Measure Information:

Title

Overall survival (OS) rate at 1 year (1Y-OS), 2 years (2Y-OS), and 3 years (3Y-OS)

Description

Time Frame

Overall survival assessment is performed at every visit from randomization of each patient until his/her death

Title

Response rate (RR)

Description

Assessment is performed by response evaluation criteria in solid tumors (RECIST) version 1.1

Time Frame

tumor assessment is performed every 6 weeks from the start of study treatment until progressive disease

Title

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

Description

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Francesco Grossi, MD

Phone

+39 010 5600385

francesco.grossi@hsanmartino.it

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Francesco Grossi, MD

Organizational Affiliation

IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro

Official's Role

Principal Investigator

Facility Information:

Facility Name

IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro

City

Genova

ZIP/Postal Code

16132

Country

Italy

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Francesco Grossi, MD

Phone

+39 010 5600385

francesco.grossi@hsanmartino.it

12. IPD Sharing Statement

Learn more about this trial

GEfitinib Plus viNOrelbine in Advanced EGFR Mutated NSCLC. GENOA Trial

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