Non Small Cell Lung CancerPhase 2NCT02319577
GEfitinib Plus viNOrelbine in Advanced EGFR Mutated NSCLC. GENOA Trial
A Phase 2 study testing oral vinorelbine and Gefitinib in people with Non Small Cell Lung Cancer, run by IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy at 1 site in Italy.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- oral vinorelbine and Gefitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteItaly
- Study dates
- Mar 2012to Dec 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 13Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro
Genova, Genova, 16132
Francesco Grossi, MD, +39 010 5600385, francesco.grossi@hsanmartino.it
About this study
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
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.
Read the 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.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- oral vinorelbine, Gefitinib
- Keywords
- NSCLC, EGFR, vinorelbine, gefitinib
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
oral vinorelbineDrug
Also called Navelbine
Anti-neoplastic drug (PO chemotherapeutical agent, vinka alkaloid)
GefitinibDrug
Also called Iressa
EGFR tyrosine kinase inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Gefitinib plus oral vinorelbine | Experimental | 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 Receives: Drug: oral vinorelbine; Drug: Gefitinib |
| Gefitinib alone | Active comparator | Arm B (21-days cycles until progressive disease or unacceptable toxicity):
Gefitinib 250 mg daily from day 1 to day 21 Receives: Drug: Gefitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months; tumor assessment is performed every 6 weeks from randomization until progressive disease
Secondary outcomes (3)
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).
Measured: Overall survival assessment is performed at every visit from randomization of each patient until his/her death
Response rate (RR)
Assessment is performed by response evaluation criteria in solid tumors (RECIST) version 1.1
Measured: tumor assessment is performed every 6 weeks from the start of study treatment until progressive disease
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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2014 (estimated)
- Study startMar 2012
- Primary completionJun 2015 (estimated)
- Study completionDec 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Francesco Grossi, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
- Investigators
- Francesco Grossi, MD, Principal investigator, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02319577
- Sponsor's protocol ID
- Genoa trial
- Status last verified
- Dec 2014
- First submitted
- 9 Dec 2014
- Last updated
- 18 Dec 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02319577
- Acronym / sponsor ID
- Genoa trial
- Conditions
- Non Small Cell Lung Cancer
- Keywords
- NSCLC, EGFR, vinorelbine, gefitinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, ItalyUniversity, hospital or other
- Study start
- Mar 2012
- Primary completion
- Jun 2015 (estimated)
- Study completion
- Dec 2015 (estimated)
- First posted
- 18 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gefitinib plus oral vinorelbine | Experimental | Drug: oral vinorelbine, Drug: GefitinibArm 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 |
| Gefitinib alone | Active comparator | Drug: GefitinibArm B (21-days cycles until progressive disease or unacceptable toxicity): Gefitinib 250 mg daily from day 1 to day 21 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Signed informed consent
- At least 18 years old
- Histologically confirmed NSCLC
- Stage IV disease
- Evidence of activating mutations of EGFR
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| oral vinorelbineAlso: NavelbineAnti-neoplastic drug (PO chemotherapeutical agent, vinka alkaloid) | Drug | Gefitinib plus oral vinorelbine |
| GefitinibAlso: IressaEGFR tyrosine kinase inhibitor | Drug | Gefitinib alone, Gefitinib plus oral vinorelbine |
Primary outcome
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.
3 secondary outcomes
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
Response rate (RR)
Time frame: tumor assessment is performed every 6 weeks from the start of study treatment until progressive disease
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francesco Grossi, MD principal investigator
IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing oral vinorelbine and Gefitinib in people with Non Small Cell Lung Cancer, run by IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Francesco Grossi, MD (+39 010 5600385, francesco.grossi@hsanmartino.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (PFS) rate at 6 months (time frame: 6 months; tumor assessment is performed every 6 weeks from randomization until progressive disease). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2014.