Neoplasms

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Gemcitabine

Docetaxel

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Gefitinib

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Antimitotic Agents

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

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Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Folinic Acid

Folate

Vitamin B9

Tyrosine

- Cisplatin + Docetaxel day 1 q 21 days for 3 cycles

* 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;

Cisplatin Docetaxel Gefitinib Pemetrexed Vinorelbine Gemcitabine

Francesco Grossi, MD

* 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.

- 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.

Customized Neoadjuvant Versus Standard Chemotherapy in NSCL Patients With Resectable Stage IIIA (N2)Disease

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)

Azienda Sanitaria Locale di Cagliari

Azienda Ospedaliera San Gerardo di Monza

Ospedale Santa Croce-Carle Cuneo

Azienda Ospedaliera S. Maria della Misericordia

Istituto Tumori Giovanni Paolo II, BARI

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 Provinciale per i Servizi Sanitari, Provincia Autonoma di Trento

Istituto Clinico Humanitas

Azienda Ospedaliera "Sant'Andrea"

Azienda Ospedaliera, Ospedale Civile di Legnano

Azienda Ospedaliera Spedali Riuniti di Livorno, Livorno

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

Chief, Lung Cancer Unit

Pleural Effusion

CBP501 25 mg/m2 + Cisplatin 75 mg/m2 + Pemetrexed 500mg/m2

CBP501, pemetrexed and cisplatin will be administered on the same day (Day 1), every 3 weeks for a maximum of six cycles. A cycle is considered to be 3 weeks (21 days).

1. CBP501 25 mg/m² will be administered as an i.v. infusion of 1 hour.
2. Pemetrexed 500 mg/m² will be administered as an i.v. infusion over 10 minutes, immediately after the CBP501 infusion.
3. Cisplatin 75 mg/m² will be administered as a 1-hour i.v. infusion immediately after the pemetrexed infusion.

CBP501 + Cisplatin + Pemetrexed

Pemetrexed and cisplatin will be administered on the same day (Day 1), every 3 weeks for a maximum of six cycles. A cycle is considered to be 3 weeks (21 days).

1. Pemetrexed 500 mg/m² will be administered as an i.v. infusion over 10 minutes.
2. Cisplatin 75 mg/m² will be administered as a 1-hour i.v. infusion immediately after the pemetrexed infusion.

Cisplatin + Pemetrexed

Takumi Kawabe, MD, PhD

This is a randomized, open-label, multicenter, phase II study to compare a triplet combination of CBP501, pemetrexed and cisplatin with pemetrexed/cisplatin when administered to patients with locally advanced (stage IIIB with malignant pleural effusion or pericardial effusion) or metastatic (stage IV) non-squamous NSCLC as consecutive i.v. infusions according to a once-every-3-weeks schedule.

The protocol will evaluate full-dose cisplatin and pemetrexed with or without CBP501. Patients will be randomized in a 1:1 ratio to pemetrexed, cisplatin and CBP501 (Arm A) or pemetrexed and cisplatin (Arm B). Randomization will be stratified according to whether or not patients are eligible for bevacizumab therapy.

Preclinical and clinical findings that support this protocol are:

* CBP501 has exhibited interesting preclinical activity in various lung cancer cell lines.
* Synergism was documented with CBP501/cisplatin in the preclinical studies with lung cancer cell lines.
* The dose-limiting toxicity (DLT) of CBP501 was rapid onset allergic reaction, as was suggested by preclinical toxicology. Other toxicities were quite limited. No evidence of potentiation of either CBP501 or cisplatin toxicity was found in the combination phase I trial, and the toxicity of the combination, primarily related to cisplatin, is manageable. It is expected that CBP501 and pemetrexed will display non-overlapping toxicity profiles in combination, given that hematological toxicity and gastrointestinal toxicity are the principal toxicity types of the latter.
* Given the acceptable safety of the cisplatin/ pemetrexed combination, it is anticipated that the addition of CBP501 to this combination can be evaluated without excessive risk in the phase II programs.
* The phase I study of CBP501 in combination with pemetrexed/cisplatin (phase I part of the mesothelioma program) did not show DLTs or evidence of enhancement of toxicities with the triplet combination. The RD of CBP501 25 mg/m², cisplatin 75 mg/m² and pemetrexed 500 mg/m² is currently in use in the phase II study with first line mesothelioma patients.
* Hints of activity were observed during the phase I study with CBP501 and cisplatin.
* No pharmacokinetics (PK) interaction was documented between cisplatin and CBP501.

This is a randomized, open-label, multicenter, phase II study to compare a triplet combination of CBP501, pemetrexed and cisplatin with pemetrexed/cisplatin when administered to patients with locally advanced (stage IIIB with malignant pleural effusion or pericardial effusion) or metastatic (stage IV) non-squamous NSCLC as consecutive i.v. infusions according to a once-every-3-weeks schedule.

The protocol will evaluate full-dose cisplatin and pemetrexed with or without CBP501. Patients will be randomized in a 1:1 ratio to pemetrexed, cisplatin and CBP501 (Arm A) or pemetrexed and cisplatin (Arm B). Randomization will be stratified according to whether or not patients are eligible for bevacizumab therapy.

The combination of cisplatin/pemetrexed has come to be recognized as the new standard of care for patients with untreated, unresectable malignant pleural mesothelioma (MPM) and untreated NSCLC non-squamous cell histology.

Preclinical and clinical findings that support this protocol are:

* CBP501 has exhibited interesting preclinical activity in various lung cancer cell lines.
* Synergism was documented with CBP501/cisplatin in the preclinical studies with lung cancer cell lines.
* The dose-limiting toxicity (DLT) of CBP501 was rapid onset allergic reaction, as was suggested by preclinical toxicology. Other toxicities were quite limited. No evidence of potentiation of either CBP501 or cisplatin toxicity was found in the combination phase I trial, and the toxicity of the combination, primarily related to cisplatin, is manageable. It is expected that CBP501 and pemetrexed will display non-overlapping toxicity profiles in combination, given that hematological toxicity and gastrointestinal toxicity are the principal toxicity types of the latter.
* Given the acceptable safety of the cisplatin/ pemetrexed combination, it is anticipated that the addition of CBP501 to this combination can be evaluated without excessive risk in the phase II programs.
* The phase I study of CBP501 in combination with pemetrexed/cisplatin (phase I part of the mesothelioma program) did not show DLTs or evidence of enhancement of toxicities with the triplet combination. The RD of CBP501 25 mg/m², cisplatin 75 mg/m² and pemetrexed 500 mg/m² is currently in use in the phase II study with first line mesothelioma patients.
* Hints of activity were observed during the phase I study with CBP501 and cisplatin.
* No pharmacokinetics (PK) interaction was documented between cisplatin and CBP501.

Triplet Combination First Line Treatment in Non Small Cell Lung Cancer (NSCLC)

Phase II Study of a Triplet Combination of CBP501, Pemetrexed and Cisplatin as First Line Treatment in Patients With Stage IV Non-squamous Non Small Cell Lung Cancer (NSCLC)

CanBas Co. Ltd.

CBP501 25 mg/m2 + Cisplatin 75 mg/m2 + Pemetrexed 500mg/m2

CBP501 + Cisplatin + Pemetrexed: CBP501, pemetrexed and cisplatin will be administered on the same day (Day 1), every 3 weeks for a maximum of six cycles. A cycle is considered to be 3 weeks (21 days).

1. CBP501 25 mg/m² will be administered as an i.v. infusion of 1 hour.
2. Pemetrexed 500 mg/m² will be administered as an i.v. infusion over 10 minutes, immediately after the CBP501 infusion.
3. Cisplatin 75 mg/m² will be administered as a 1-hour i.v. infusion immediately after the pemetrexed infusion.

A CBP501 +Cisplatin + Pemetrexed

Cisplatin + Pemetrexed

Cisplatin + Pemetrexed: Pemetrexed and cisplatin will be administered on the same day (Day 1), every 3 weeks for a maximum of six cycles. A cycle is considered to be 3 weeks (21 days).

1. Pemetrexed 500 mg/m² will be administered as an i.v. infusion over 10 minutes.
2. Cisplatin 75 mg/m² will be administered as a 1-hour i.v. infusion immediately after the pemetrexed infusion.

B Cisplatin + Pemetrexed

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

The Primary Efficacy Endpoint is Progression Free Survival, Analyzed in the Treated Population. PFS is Assessed From Randomization Until Either Tumor Progression, as Per RECIST Criteria, or Until Death Due to Any Reason.

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Customized Neoadjuvant Versus Standard Chemotherapy in NSCL Patients With Resectable Stage IIIA (N2)Disease	NCT01784549	Non Small Cell ...	Cisplatin Docet...	18 Years -	IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Customized Neoadjuvant Versus Standard Chemotherapy in NSCL Patients With Resectable Stage IIIA (N2)Disease	NCT01784549	Non Small Cell ...	Cisplatin Docet...	18 Years -	IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Triplet Combination First Line Treatment in Non Small Cell Lung Cancer (NSCLC)	NCT00942825	Metastatic Non-...	CBP501 + Cispla... Cisplatin + Pem...	18 Years -	CanBas Co. Ltd.

Spots Global Cancer Trial Database for nscl

Every month we try and update this database with for nscl cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for nscl

Every month we try and update this database with for nscl cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for nscl cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.