Metastatic Non-squamous Non Small Cell Lung Cancer Clinical Trial
Official title:
Phase II Study of a Triplet Combination of CBP501, Pemetrexed and Cisplatin as First Line Treatment in Patients With Locally Advanced (Stage IIIB With Malignant Pleural Effusion or Pericardial Effusion) or Metastatic (Stage IV) Non-squamous Non Small Cell Lung Cancer (NSCLC)
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.
n/a
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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