Non Small Cell Lung CancerPhase 2CONTESTNCT01784549
Customized Neoadjuvant Versus Standard Chemotherapy in NSCL Patients With Resectable Stage IIIA (N2)Disease
A Phase 2 study testing Cisplatin Docetaxel Gefitinib Pemetrexed Vinorelbine Gemcitabine 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
The investigators hypothesized that NSCL patients receiving therapy based on their baseline tumor markers levels would attain higher response rates than patients in the control arm receiving non customized therapy. 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?
- Cisplatin Docetaxel Gefitinib Pemetrexed Vinorelbine Gemcitabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 168 participants
- Where
- 1 siteItaly
- Study dates
- Jul 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
- Provision of a signed and dated written informed consent document prior to any study specific procedures.
- Age ≥18 years, male or female.
- Histologically confirmed NSCLC.
- Specimen tumor tissue obtained from mediastinoscopy
- ECOG Performance status (PS) 0-1.
- Stage IIIA(N2) patients with technical operable disease limited to T1a,b, T2a,b N2 M0; T3 (>7 cm) N2 M0.
Show all 18Show fewer
- Medically fit for resection by lobectomy or pneumonectomy.
- Radiologically measurable disease (RECIST v1.1 criteria).
- Prior surgery for NSCLC if resected ≥5 years.
- No prior chemotherapy, targeted-therapy, investigational therapy or radiation for NSCLC.
- No uncontrolled medical problems.
- No superior vena cava syndrome.
- Peripheral neuropathy must be ≤ grade 1.
- Acceptable hematologic and chemistry parameters.
- Creatinine clearance >50 ml/min.
- Female patients or their partners must be surgically sterile or be postmenopausal, or agree to use effective contraception while in trial treatment and for 3 months thereafter.
- Female patients with reproductive potential must have a negative pregnancy test (serum or urine) within 72 hours prior to starting treatment.
- Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures including patient reported measures.
Who cannot join
- Any evidence of mixed histology including elements of small cell or carcinoid lung cancer.
- Stage IIIA patients limited to T3 N1 M0; T3 (invasion) N2 M0; T4 N0, N1 M0.
- Any clinically significant GI abnormalities, which may impair intake, transit or absorption of gefitinib, such as the inability to take oral medication.
- Current enrollment in another therapeutic clinical trial.
- Any psychiatric or cognitive disorder that would limit the understanding or rendering of informed consent and/or compromise compliance with the requirements of this study.
- Past medical history of interstitial lung disease, drug-induced interstitial disease, radiation pneumonitis which required steroid treatment or any evidence of clinically active interstitial lung disease
Show all 20Show fewer
- Pre-existing idiopathic pulmonary fibrosis evidence by computerized tomography (CT) scan at baseline.
- Uncontrolled or significant CV disease, including: myocardial infarction within 12 months; uncontrolled angina within 6 months; congestive heart failure within 6 months; diagnosed or suspected congenital long QT syndrome;
- Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes);
- Prolonged QTc interval on pre entry ECG.
- Any history of second or third degree heart block (may be eligible if currently have a pacemaker);
- Heart rate <50/minute on baseline ECG;
- Uncontrolled hypertension.
- Evidence of prior malignancy (other than non melanoma skin cancer or in situ cervical cancer, or localized and presumed cured prostate cancer with PSA < ULN) within the last 3 years.
- Other severe acute or chronic medical condition that may increase the risk associated with trial participation or may interfere with the interpretation of trial results and, in the judgment of the investigator.
- Patients in whom corticosteroid premedication was contraindicated.
- HIV-positive patients on active treatment.
- Medications are prohibited at baseline and prior to randomization if they affect the pharmacokinetics of gefitinib, cisplatin, docetaxel, gemcitabine, vinorelbine and pemetrexed or if they are mainly metabolized by CYP3A4.
- Patients who are otherwise eligible can be enrolled only if drug substitution is performed with acceptable clinical outcome prior to enrollment: known severe hypersensitivity to gefitinib or other chemotherapeutic agents or any of the excipients of the products.
- Pregnancy or breast-feeding.
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
Genoa, 16132
Francesco Grossi, MD, +393355255484, fg1965@libero.it
About this study
Official title: A Multi-center Phase II Randomized Study of Customized Neoadjuvant Therapy Versus Standard Chemotherapy in Non-small Cell Lung Cancer (NSLC) Patients With Resectable Stage IIIA (N2) Disease (CONTEST-TRIAL)
- The investigators hypothesized that NSCL patients receiving therapy based on their baseline tumor markers levels would attain higher response rates than patients in the control arm receiving non customized therapy.
- patients with stage IIIA(N2) NSCLC will be randomized in a 2:1 ratio to customized therapy based on biomarkers status (ERCC1, RRM1, TS and EGFR mutation) vs standard chemotherapy.
- The primary objective of this multicenter trial is to compare pathological complete response of all subjects randomized, by treatment arm.
- Secondary objectives are to compare all randomized subjects by treatment arm for: response rate, disease-free survival, overall survival, one, two and three year survival and safety profile.
The study is expected to demonstrate both the feasibility of this approach and the logistic problems associated with a biomarker-driven therapeutic strategy in NSCLC.
Read the detailed description
- Subjects will be stratified by histology and biological markers (ERCC1, RRM1, TS, EGFR mutation). Randomization will be centralized at the coordinating centre site. Patients will receive chemotherapy with cisplatin + docetaxel or customized therapy for 3 cycles (60 days with gefitinib) before surgery.
Every 4 months for 3 years and then every 6 months for 2 years following surgery, subjects will be assessed by the investigator for adverse events related to study drug, documentation of post study therapies received, DFS, and survival.
- Periodic evaluations of the trial data will be conducted by an independent data monitoring committee to ensure subject safety and the validity and scientific merit of the study.
Assuming that the study is not stopped at the planned futility analyses or for safety reasons, the final analysis will take place after the targeted number of events (pathological complete response) is reached, which is estimated to take place 24 months post study initiation.
- The pathological complete response (pCR)in the two groups will be computed in the ITT populations and compared by means of the chi-square test without continuity correction. For exploratory purposes, a multivariate logistic regression model will be fitted to the data, with the pCR as the response variable and treatment (standard/ experimental) and histo/molecular subgroup as covariate. The heterogeneity of the relative efficacy of the tailored approach in the various subgroups (=subgroup analysis) will be evaluated by including in the model the appropriate set of treatment-by-subgroup interaction terms, using the standard likelihood ratio test. Time-to-event analyses (DFS and OS) will use standard Kaplan-Meier estimators (with the Log-rank test) and semi-parametric PH regression models. Safety will be summarized based on adverse events, vital signs and laboratory assessments. A group sequential design is used to compare the Overall Survival in the two study arms.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- Cisplatin Docetaxel Gefitinib Pemetrexed Vinorelbine Gemcitabine
- Keywords
- NSCL, biomarkers, Customized Neoadjuvant Therapy
- 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.
Cisplatin Docetaxel Gefitinib Pemetrexed Vinorelbine GemcitabineDrug
| Study group | Role | What they receive |
|---|---|---|
| Cisplatin Docetaxel | Active comparator | - Cisplatin + Docetaxel day 1 q 21 days for 3 cycles Receives: Drug: Cisplatin Docetaxel Gefitinib Pemetrexed Vinorelbine Gemcitabine |
| Gefitinib Pemetrexed Vinorelbine Gemcitabine | Experimental | * Gefitinib day for 8 wks;
* Pemetrexed day 1 q 21 days for 3 cycles;
* Docetaxel day 1 + Vinorelbine days 1,8 q 21 days for 3 cycles;
* Docetaxel days 1,8 + Gemcitabine days 1,8 q 21 days for 3 cycles;
* Cisplatin + Docetaxel day 1 q 21 days for 3 cycles;
* Cisplatin day 1+ Gemcitabine days 1,8 q 21 days for 3 cycles; Receives: Drug: Cisplatin Docetaxel Gefitinib Pemetrexed Vinorelbine Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic Complete Response
Measured: 30 days
Secondary outcomes (3)
Overall Survival (OS)
Measured: at 1, 2, and 5 years
Disease-Free Survival (DFS)
Measured: at 1, 2, and 5 years
Overall Response (OR)
Measured: at 1, 2, and 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2013 (estimated)
- Study startJul 2012
- Primary completionOct 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
- 168 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
- Collaborators
- Azienda Sanitaria Locale di Cagliari, Azienda Ospedaliera San Gerardo di Monza, Ospedale Santa Croce-Carle Cuneo, Azienda Ospedaliera S. Maria della Misericordia, Istituti Tumori Giovanni Paolo II, Azienda Ospedaliera dei Colli Monaldi-Cotugno-CTO, Napoli, Azienda Ospedaliera Santa Maria Degli Angeli, Azienda Ospedaliera San Camillo Forlanini, Azienda Ospedaliera San Giovanni Battista, Azienda Ospedaliera Universitaria Integrata Verona, Azienda Sanitaria Locale n.2 Savonese, ASL TO4, Chivasso, Azienda Sanitaria Universitaria Integrata del Trentino, Istituto Clinico Humanitas, Azienda Ospedaliera "Sant'Andrea", Azienda Ospedaliera, Ospedale Civile di Legnano, Azienda Ospedaliera Spedali Riuniti di Livorno, Livorno
- 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, Genoa, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01784549
- Sponsor's protocol ID
- CONTEST TRIAL RF-2009-1530324
- Other IDs
- 2011-005267-24
- Acronym
- CONTEST
- Status last verified
- Nov 2014
- First submitted
- 2 Feb 2013
- Last updated
- 25 Nov 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center Phase II Randomized Study of Customized Neoadjuvant Therapy Versus Standard Chemotherapy in Non-small Cell Lung Cancer (NSLC) Patients With Resectable Stage IIIA (N2) Disease (CONTEST-TRIAL)
- ClinicalTrials.gov ID
- NCT01784549
- Acronym / sponsor ID
- CONTEST / CONTEST TRIAL RF-2009-1530324
- Conditions
- Non Small Cell Lung Cancer
- Keywords
- NSCL, biomarkers, Customized Neoadjuvant Therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 168 participants (estimated)
- Lead sponsor
- IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, ItalyUniversity, hospital or other
- Collaborators
- Azienda Sanitaria Locale di Cagliari, Azienda Ospedaliera San Gerardo di Monza, Ospedale Santa Croce-Carle Cuneo, Azienda Ospedaliera S. Maria della Misericordia, Istituti Tumori Giovanni Paolo II, Azienda Ospedaliera dei Colli Monaldi-Cotugno-CTO, Napoli, Azienda Ospedaliera Santa Maria Degli Angeli, Azienda Ospedaliera San Camillo Forlanini, Azienda Ospedaliera San Giovanni Battista, Azienda Ospedaliera Universitaria Integrata Verona, Azienda Sanitaria Locale n.2 Savonese, ASL TO4, Chivasso, Azienda Sanitaria Universitaria Integrata del Trentino, Istituto Clinico Humanitas, Azienda Ospedaliera "Sant'Andrea", Azienda Ospedaliera, Ospedale Civile di Legnano, Azienda Ospedaliera Spedali Riuniti di Livorno, Livorno
- Study start
- Jul 2012
- Primary completion
- Oct 2015 (estimated)
- Study completion
- Dec 2015 (estimated)
- First posted
- 6 Feb 2013 (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.
- The investigators hypothesized that NSCL patients receiving therapy based on their baseline tumor markers levels would attain higher response rates than patients in the control arm receiving non customized therapy.
- patients with stage IIIA(N2) NSCLC will be randomized in a 2:1 ratio to customized therapy based on biomarkers status (ERCC1, RRM1, TS and EGFR mutation) vs standard chemotherapy.
- The primary objective of this multicenter trial is to compare pathological complete response of all subjects randomized, by treatment arm.
- Secondary objectives are to compare all randomized subjects by treatment arm for: response rate, disease-free survival, overall survival, one, two and three year survival and safety profile.
The study is expected to demonstrate both the feasibility of this approach and the logistic problems associated with a biomarker-driven therapeutic strategy in NSCLC.
Detailed description
- Subjects will be stratified by histology and biological markers (ERCC1, RRM1, TS, EGFR mutation). Randomization will be centralized at the coordinating centre site. Patients will receive chemotherapy with cisplatin + docetaxel or customized therapy for 3 cycles (60 days with gefitinib) before surgery.
Every 4 months for 3 years and then every 6 months for 2 years following surgery, subjects will be assessed by the investigator for adverse events related to study drug, documentation of post study therapies received, DFS, and survival.
- Periodic evaluations of the trial data will be conducted by an independent data monitoring committee to ensure subject safety and the validity and scientific merit of the study.
Assuming that the study is not stopped at the planned futility analyses or for safety reasons, the final analysis will take place after the targeted number of events (pathological complete response) is reached, which is estimated to take place 24 months post study initiation.
- The pathological complete response (pCR)in the two groups will be computed in the ITT populations and compared by means of the chi-square test without continuity correction. For exploratory purposes, a multivariate logistic regression model will be fitted to the data, with the pCR as the response variable and treatment (standard/ experimental) and histo/molecular subgroup as covariate. The heterogeneity of the relative efficacy of the tailored approach in the various subgroups (=subgroup analysis) will be evaluated by including in the model the appropriate set of treatment-by-subgroup interaction terms, using the standard likelihood ratio test. Time-to-event analyses (DFS and OS) will use standard Kaplan-Meier estimators (with the Log-rank test) and semi-parametric PH regression models. Safety will be summarized based on adverse events, vital signs and laboratory assessments. A group sequential design is used to compare the Overall Survival in the two study arms.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cisplatin Docetaxel | Active comparator | Drug: Cisplatin Docetaxel Gefitinib Pemetrexed Vinorelbine Gemcitabine- Cisplatin + Docetaxel day 1 q 21 days for 3 cycles |
| Gefitinib Pemetrexed Vinorelbine Gemcitabine | Experimental | Drug: Cisplatin Docetaxel Gefitinib Pemetrexed Vinorelbine Gemcitabine* Gefitinib day for 8 wks; * Pemetrexed day 1 q 21 days for 3 cycles; * Docetaxel day 1 + Vinorelbine days 1,8 q 21 days for 3 cycles; * Docetaxel days 1,8 + Gemcitabine days 1,8 q 21 days for 3 cycles; * Cisplatin + Docetaxel day 1 q 21 days for 3 cycles; * Cisplatin day 1+ Gemcitabine days 1,8 q 21 days for 3 cycles; |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Provision of a signed and dated written informed consent document prior to any study specific procedures.
- Age ≥18 years, male or female.
- Histologically confirmed NSCLC.
- Specimen tumor tissue obtained from mediastinoscopy
- ECOG Performance status (PS) 0-1.
Key exclusion criteria (20 listed)
- Any evidence of mixed histology including elements of small cell or carcinoid lung cancer.
- Stage IIIA patients limited to T3 N1 M0; T3 (invasion) N2 M0; T4 N0, N1 M0.
- Any clinically significant GI abnormalities, which may impair intake, transit or absorption of gefitinib, such as the inability to take oral medication.
- Current enrollment in another therapeutic clinical trial.
- Any psychiatric or cognitive disorder that would limit the understanding or rendering of informed consent and/or compromise compliance with the requirements of this study.
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 |
|---|---|---|
| Cisplatin Docetaxel Gefitinib Pemetrexed Vinorelbine Gemcitabine | Drug | Cisplatin Docetaxel, Gefitinib Pemetrexed Vinorelbine Gemcitabine |
Primary outcome
Pathologic Complete Response
Time frame: 30 days
3 secondary outcomes
Overall Survival (OS)
Time frame: at 1, 2, and 5 years
Disease-Free Survival (DFS)
Time frame: at 1, 2, and 5 years
Overall Response (OR)
Time frame: at 1, 2, and 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2014.
Related trials for Non Small Cell Lung Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
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, Genoa, Italy
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 Cisplatin Docetaxel Gefitinib Pemetrexed Vinorelbine Gemcitabine 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 18 inclusion and 20 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 25 Nov 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 (+393355255484, fg1965@libero.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathologic Complete Response (time frame: 30 days). 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 25 Nov 2014.