Clinical trial NCT00942825
Conditions: Metastatic Non-squamous Non Small Cell Lung Cancer
Keywords: NSCL non-squamous non small cell lung cancer Lung Cancer Lung non-squamous metastatic pleural effusion Stage IIIb Stage IV NSCLC
Sponsor: CanBas Co. Ltd.
Start date: 2009-04-01; Completion date: 2013-07-01
Enrollment: 195 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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.

Detailed description:
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.

Arms: arm 1: CBP501 25 mg/m2 + Cisplatin 75 mg/m2 + Pemetrexed 500mg/m2 arm 2: Cisplatin + Pemetrexed
Interventions: intervention 1: CBP501 + Cisplatin + Pemetrexed intervention 2: Cisplatin + Pemetrexed
Intervention descriptions: intervention 1: 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. intervention 2: 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.

Protocol documents: