Clinical trial NCT01714037: 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]
Official title: A Phase I-II Evaluation of the Safety and Efficacy of the Oral HSP90 Inhibitor Debio 0932 in Combination With Standard of Care in first-and Second-line Therapy of Patients With Stage IIIb or IV Non-small Cell Lung Cancer-the HALO Study (HSP90 Inhibition And Lung Cancer Outcomes)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non-small Cell Lung Cancer
Keywords: Safety
Efficacy
HSP90
Debio 0932
Standard of care treatment, NSCLC
Lead sponsor: Debiopharm International SA
Sponsor class: INDUSTRY
Collaborators: name: Syneos Health
First posted: 2012-10-25
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Occurrence of Dose Limiting Toxicities
timeFrame: 6 weeks
Secondary outcomes:
measure: Change in vital signs and Eastern Cooperative Oncology Group Performance Status (ECOG PS)
timeFrame: Day 1 of each treatment cycle until disease progression or study drug toxicity
measure: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Every treatment cycle until disease progression or study drug toxicity
measure: Incidence of laboratory abnormalities
timeFrame: 2 to 4 times every treatment cycle until disease progression or study drug toxicity
measure: Incidence of treatment discontinuations due to AEs and SAEs
timeFrame: Every treatment cycle until diseases progression or study drug toxicity
measure: Change in left ventricular ejection fraction (LVEF)
timeFrame: Baseline and after 4 weeks of treatment
measure: Pharmacokinetic parameters of Debio 0932 and its metabolite Debio 0932-MET1
timeFrame: 22 days
measure: Pharmacokinetic parameters of cisplatin/pemetrexed, cisplatin/gemcitabine, and docetaxel
timeFrame: 22 days
measure: Best overall tumor response
timeFrame: 22 days
measure: Pharmacodynamic biomarkers
timeFrame: 22 days
measure: Pharmacogenomic, tumour pharmacogenetic, proteomic, and pharmacogenetic factors predictive of response to Debio 0932
timeFrame: 7 days
Other outcomes:
Locations:
city: Dijon
country: France
facility: Centre GF Leclerc
city: Lyon
country: France
facility: Centre Léon Bérard
city: Nantes
country: France
facility: Institut de Cancérologie de l'Ouest- Institut René Gauduchau
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Puerta de Hierro Majadahonda
city: Seville
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Newcastle
country: United Kingdom
facility: Freeman Hospital
Study officials:
affiliation: Centre GF Leclerc, Dijon, France
name: Nicolas Isambert, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut Claudius Regaud, Toulouse, France
name: Jean-Pierre Delord, PR
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Léon Bérard, Lyon, France
name: Jèrôme Fayette, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut de Cancérologie de l'Ouest- Institut René Gauduchau, Nantes, France
name: Jaafar Bennouma, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Virgen del Rocío, Seville, Spain
name: Luis Paz-Ares, PR
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitari Vall d'Hebron, Barcelone, Spain
name: Enriqueta Felip, PR
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Puerta de Hierro Majadahonda, Madrid, Spain
name: Mariano Provencio, PR
role: PRINCIPAL_INVESTIGATOR
affiliation: Freeman Hospital, Newcastle, UK
name: Ruth Plummer, PR
role: PRINCIPAL_INVESTIGATOR
References: