Non-small Cell Lung Cancer
Conditions
Keywords
Safety, Efficacy, HSP90, Debio 0932, Standard of care treatment, NSCLC
Brief summary
Part A of this study will investigate the Maximum Tolerated Dose of Debio 0932 in combination with standard of care chemotherapy for the first- and second-line treatment of advanced NSCLC.
Detailed description
Part A of this study will determine the Maximum Tolerated Dose of Debio 0932 in combination with cisplatin/pemetrexed and cisplatin/gemcitabine in treatment-naïve patients with Stage IIIb or IV NSCLC, and with docetaxel in previously treated patients with Stage IIIb or IV NSCLC. Escalating doses of Debio 0932 will be given to subsequent patients in combination with standard doses of these 3 background chemotherapies.
Interventions
DRUGDebio 0932
Debio 0932 will be administered as daily oral tablets at a starting dose of 250 mg four times per day (QD).
DRUGCisplatin
Cisplatin 75 mg/m2 body surface area (BSA) will be administered on Day 1 of each 21-day treatment cycle.
DRUGPemetrexed
Pemetrexed 500 mg/m2 BSA will be administered on Day 1 of each 21 day treatment cycle.
DRUGGemcitabine
Gemcitabine 1250 mg/m2 BSA will be administered on Days 1 and 8 of each 21-day treatment cycle.
DRUGDocetaxel
Docetaxel 60 or 75 mg/m2 BSA will be administered on Day 1 of each 21-day treatment cycle.
Sponsors
Syneos Health
Debiopharm International SA
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of NSCLC with confirmed squamous or non-squamous tumour histology, without known epidermal growth factor receptor (EGFR) mutation * Advanced or metastatic disease (Stage IIIb or IV) * Patients to be treated with cisplatin/gemcitabine or cisplatin/pemetrexed: No previous systemic treatment with chemotherapy, targeted therapy or investigational agents (except adjuvant therapy if \> 6 months ago); Patients to be treated with docetaxel: ≥ 1 previous treatment with chemotherapy * Measurable disease by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria * ECOG performance score 0-1 * Life expectancy ≥ 3 months * Adequate bone marrow-, renal- and hepatic function * LVEF ≥ 55% on cardiac ultrasound
Exclusion criteria
* Symptomatic brain metastases * Gastro-intestinal disorders that could affect drug absorption (including, but not limited to, major abdominal surgery, significant bowel obstruction, ulcerative colitis, Crohn's disease) * Concurrent treatment with any other systemic anti-cancer therapy * Serious concomitant uncontrolled medical conditions
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence of Dose Limiting Toxicities | 6 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Every treatment cycle until disease progression or study drug toxicity |
| Incidence of laboratory abnormalities | 2 to 4 times every treatment cycle until disease progression or study drug toxicity |
| Incidence of treatment discontinuations due to AEs and SAEs | Every treatment cycle until diseases progression or study drug toxicity |
| Change in left ventricular ejection fraction (LVEF) | Baseline and after 4 weeks of treatment |
| Change in vital signs and Eastern Cooperative Oncology Group Performance Status (ECOG PS) | Day 1 of each treatment cycle until disease progression or study drug toxicity |
| Pharmacokinetic parameters of cisplatin/pemetrexed, cisplatin/gemcitabine, and docetaxel | 22 days |
| Best overall tumor response | 22 days |
| Pharmacodynamic biomarkers | 22 days |
| Pharmacogenomic, tumour pharmacogenetic, proteomic, and pharmacogenetic factors predictive of response to Debio 0932 | 7 days |
| Pharmacokinetic parameters of Debio 0932 and its metabolite Debio 0932-MET1 | 22 days |
Countries
France, Spain, United Kingdom
Outcome results
None listed