A Clinical Study on the Safety and Efficacy of Debio 0932 in Combination With Standard of Care in Patients With Non-small Cell Lung Cancer [NSCLC]

Phase 1

Terminated

• Conditions: Non-small Cell Lung Cancer
• Interventions: Drug: Debio 0932; Drug: Cisplatin; Drug: Docetaxel; Drug: Gemcitabine; Drug: Pemetrexed

• Registration Number: NCT01714037
• Lead Sponsor: Debiopharm International SA

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.

Study Timeline

• Study Start: 2012-08
• Study First Submitted: 2012-10-03
• Study First Submitted QC: 2012-10-23
• Study First Posted: 2012-10-25
• Primary Completion: 2014-11
• Study Completion: 2014-11
• Status Verified: 2015-04
• Last Update Submitted: 2015-04-07
• Last Update Posted: 2015-04-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 82

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cisplatin, Gemcitabine, Debio 0932	Cisplatin	Cisplatin, Gemcitabine, Debio 0932
Cisplatin, Pemetrexed, Debio 0932	Debio 0932	Cisplatin, Pemetrexed, Debio 0932
Cisplatin, Gemcitabine, Debio 0932	Gemcitabine	Cisplatin, Gemcitabine, Debio 0932
Docetaxel, Debio 0932	Debio 0932	Docetaxel, Debio 0932
Cisplatin, Pemetrexed, Debio 0932	Cisplatin	Cisplatin, Pemetrexed, Debio 0932
Cisplatin, Pemetrexed, Debio 0932	Pemetrexed	Cisplatin, Pemetrexed, Debio 0932
Cisplatin, Gemcitabine, Debio 0932	Debio 0932	Cisplatin, Gemcitabine, Debio 0932
Docetaxel, Debio 0932	Docetaxel	Docetaxel, Debio 0932

Primary Outcome Measures

Name	Time	Method
Occurrence of Dose Limiting Toxicities	6 weeks

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic parameters of Debio 0932 and its metabolite Debio 0932-MET1	22 days
Pharmacodynamic biomarkers	22 days
Change in left ventricular ejection fraction (LVEF)	Baseline and after 4 weeks of treatment
Best overall tumor response	22 days
Pharmacogenomic, tumour pharmacogenetic, proteomic, and pharmacogenetic factors predictive of response to Debio 0932	7 days
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
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
Pharmacokinetic parameters of cisplatin/pemetrexed, cisplatin/gemcitabine, and docetaxel	22 days

Trial Locations

Locations (8)

Centre GF Leclerc; 🇫🇷 Dijon, France

Institut de Cancérologie de l'Ouest- Institut René Gauduchau; 🇫🇷 Nantes, France

Centre Léon Bérard; 🇫🇷 Lyon, France

Institut Claudius Regaud; 🇫🇷 Toulouse, France

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Puerta de Hierro Majadahonda; 🇪🇸 Madrid, Spain

Hospital Universitario Virgen del Rocío; 🇪🇸 Seville, Spain

Freeman Hospital; 🇬🇧 Newcastle, United Kingdom