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] (HALO)

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)

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.

Study Overview

• Status: Terminated
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Debio 0932; Drug: Cisplatin; Drug: Pemetrexed; Drug: Gemcitabine; Drug: Docetaxel

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 Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Dijon, France
    • Centre GF Leclerc
  • Lyon, France
    • Centre Léon Bérard
  • Nantes, France
    • Institut de Cancérologie de l'Ouest- Institut René Gauduchau
  • Toulouse, France
    • Institut Claudius Regaud
• Spain
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain
    • Hospital Puerta de Hierro Majadahonda
  • Seville, Spain
    • Hospital Universitario Virgen del Rocío
• United Kingdom
  • Newcastle, United Kingdom
    • Freeman Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cisplatin, Pemetrexed, Debio 0932	Drug: Debio 0932; Debio 0932 will be administered as daily oral tablets at a starting dose of 250 mg four times per day (QD).; Drug: Cisplatin; Cisplatin 75 mg/m2 body surface area (BSA) will be administered on Day 1 of each 21-day treatment cycle.; Drug: Pemetrexed; Pemetrexed 500 mg/m2 BSA will be administered on Day 1 of each 21 day treatment cycle.
Experimental: Cisplatin, Gemcitabine, Debio 0932	Drug: Debio 0932; Debio 0932 will be administered as daily oral tablets at a starting dose of 250 mg four times per day (QD).; Drug: Cisplatin; Cisplatin 75 mg/m2 body surface area (BSA) will be administered on Day 1 of each 21-day treatment cycle.; Drug: Gemcitabine; Gemcitabine 1250 mg/m2 BSA will be administered on Days 1 and 8 of each 21-day treatment cycle.
Experimental: Docetaxel, Debio 0932	Drug: Debio 0932; Debio 0932 will be administered as daily oral tablets at a starting dose of 250 mg four times per day (QD).; Drug: Docetaxel; Docetaxel 60 or 75 mg/m2 BSA will be administered on Day 1 of each 21-day treatment cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Occurrence of Dose Limiting Toxicities	6 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
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
Change in left ventricular ejection fraction (LVEF)	Baseline and after 4 weeks of treatment
Pharmacokinetic parameters of Debio 0932 and its metabolite Debio 0932-MET1	22 days
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

Collaborators and Investigators

• Sponsor: Debiopharm International SA
• Collaborators: Syneos Health
• Investigators: Principal Investigator: Nicolas Isambert, MD, Centre GF Leclerc, Dijon, France; Principal Investigator: Jean-Pierre Delord, PR, Institut Claudius Regaud, Toulouse, France; Principal Investigator: Jèrôme Fayette, MD, Centre Léon Bérard, Lyon, France; Principal Investigator: Jaafar Bennouma, MD, Institut de Cancérologie de l'Ouest- Institut René Gauduchau, Nantes, France; Principal Investigator: Luis Paz-Ares, PR, Hospital Universitario Virgen del Rocío, Seville, Spain; Principal Investigator: Enriqueta Felip, PR, Hospital Universitari Vall d'Hebron, Barcelone, Spain; Principal Investigator: Mariano Provencio, PR, Hospital Puerta de Hierro Majadahonda, Madrid, Spain; Principal Investigator: Ruth Plummer, PR, Freeman Hospital, Newcastle, UK

Publications and helpful links

Helpful Links

• Site Debiopharm SA

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: October 3, 2012
• First Submitted That Met QC Criteria: October 23, 2012
• First Posted (Estimate): October 25, 2012

Study Record Updates

• Last Update Posted (Estimate): April 8, 2015
• Last Update Submitted That Met QC Criteria: April 7, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Safety; Efficacy; HSP90; Debio 0932; Standard of care treatment, NSCLC
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Folic Acid Antagonists; Gemcitabine; Docetaxel; Cisplatin; Pemetrexed
• Other Study ID Numbers: Debio 0932-201