| General information |
| Database: | DB00889 |
| Objective: | PKC412 (Nbenzoylstaurosporine), an oral inhibitor of protein kinase C, is capable of cell cycle inhibition and is endotheyd with antiangiogenic properties. This dosefindingphase I study was designed to establish the maximum tolerated dose (MTD) of PKC412 when combined with cisplatingemcitabine. |
| Authors: | Monnerat C, et al |
| Title: | Phase I study of PKC412 (Nbenzoylstaurosporine), a novel oral protein kinase C inhibitor, combined with gemcitabine and cisplatin in patients with non small cell lung cancer. |
| Journal: | Ann Oncol. |
| Year: | 2004 |
| PMID: | 14760128 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | PKC412
|
| Target: | mRNA of MCL1
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | non small cell lung cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | PKC412 combined with gemcitabine + cisplatin |
| Study Type: | dosefindingphase I study |
| Key Patients Feature: | Patients with histologicallyproven stage IIIB-IV non small cell lung cancer who were suitable for cisplatin and gemcitabine chemotherapy were eligible for entry onto the study |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Escalating doses of PKC412 were given every day of a 4 week cycle with cisplatin 100 mg/m2 on day 2 and gemcitabine 1000 mg/m2 on days 1, 8 and 15 in patients with non small cell lung cancer. Dose escalation was based on a modified continuous reassessment method. |
| Primary End Point: | MTD, and toxicity |
| Secondary End Point: | NA |
| Patients Number: | 23 |
| Trial Results |
| DLT_MTD: | DLTs were defined as grade 4 neutropenia lasting at least 7 days, grade 4 febrile neutropenia, grade 4 thrombocytopenia, grade more than and equal to 2 nephrotoxicity and any other grade 3-4 nonhematological toxicity (excepted alopecia and acute nausea/vomiting).The MTD was defined as the highest dose of PKC412 at which >35% of the patient population would experience DLT during cycle 1. |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | the toxicities commonly observed were hematological. Cisplatin-gemcitabinerelated hematological toxicities stratified according to PKC412 dose levels are listed in Table 3. Of the 207 scheduled gemcitabine administrations, dose reduction and omission were necessary in 20% and 29% of cycles, respectively. |
| Conclusions: | The results of the present study indicate that PKC412 at a dose of 50 mgday can be safely added to cisplatin and gemcitabine in patients with advanced non small cell lung cancer. |