Clinical trial NCT00682981: A Phase I/II Study of Carboplatin and Etoposide With or Without Obatoclax in Extensive-stage Small Cell Lung Cancer (ES-SCLC)
Official title: A Phase I Followed by a Randomized, Phase II Study of Carboplatin and Etoposide With or Without Obatoclax Administered Every 3 Weeks to Patients With Extensive- Stage Small Cell Lung Cancer (ES-SCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Extensive-stage Small Cell Lung Cancer
Keywords: ES-SCLC
Obatoclax
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Cephalon
First posted: 2008-05-23
Enrollment: 218
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The Phase I portion of this protocol will determine the best phase II dose and schedule of obatoclax with carboplatin and etoposide in patients with extensive-stage small cell lung cancer. The Phase II portion will evaluate the response rate to this regimen.

Detailed description: In the Phase I portion, both 3 hour and 24 hour infusions of obatoclax with carboplatin and etoposide every 3 weeks will be evaluated at different doses. In the Phase II portion, 3 hour infusions of obatoclax with or without carboplatin and etoposide every three weeks will be evaluated for response rates.

Eligibility criteria: Inclusion Criteria:

Phase I:

* Pathological or cytological confirmation of SCLC
* ES-SCLC
* Measurable disease using Response Evaluation Criteria in Solid Tumors (RECIST) with at least one lesion ≥2.0 cm using conventional technique or ≥1.0 cm with spiral computed tomography (CT) scan in a single dimension
* No previous chemotherapy
* Age ≥18 years
* Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1
* Normal organ function defined as: absolute neutrophil count (ANC)

  * 1500/mm3, platelets ≥100,000/mm3, total bilirubin ≤ upper limit of normal (ULN) or total bilirubin ≤ 3.0 if liver metastases are present, alanine aminotransferase (serum glutamic pyruvic transaminase) (ALT \[SGPT\])

    * 2.5 ´ ULN or ALT/SGPT ≤ 5 ´ ULN if liver metastases are present, and creatinine within normal institutional limits or calculated creatinine clearance ≥50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
* Negative serum or urine pregnancy test result prior to study entry. In addition, women of child-bearing potential and men with partners of child-bearing potential must agree to use acceptable forms of birth control (those that result in less than 1% pregnancy/year when used correctly: implants, injectables, combined oral contraceptives, some IUDs, vasectomy of a male partner, sexual abstinence)
* Ability to understand and willingness to sign a written informed consent form

Phase II:

* Pathological or cytological confirmation of SCLC
* ES-SCLC
* Measurable disease using RECIST criteria with at least one lesion

  * 2.0 cm using conventional technique or ≥1.0 cm with spiral CT scan in a single dimension
* No previous chemotherapy
* Age ≥18 years
* ECOG Performance Status ≤2;
* Normal organ function defined as: ANC ≥1500/mm3, platelets ≥100,000/mm3, total bilirubin ≤ULN or total bilirubin ≤ 3.0 if liver metastases are present, ALT (SGPT) ≤2.5 ´ ULN or ALT/SGPT ≤ 5 ´ ULN if liver metastases are present, and creatinine within normal institutional limits or calculated creatinine clearance ≥50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
* Negative serum or urine pregnancy test result prior to study entry. In addition, women of child-bearing potential and men with partners of child-bearing potential must agree to use acceptable forms of birth control (those that result in less than 1% pregnancy/year when used correctly: implants, injectables, combined oral contraceptives, some IUDs, vasectomy of a male partner, sexual abstinence)
* Ability to understand and willingness to sign a written informed consent form

Exclusion Criteria:

Phase I and II:

* Other investigational or commercial agents or therapies administered with the intent to treat the patient's malignancy
* History of allergic reactions attributed to components of the obatoclax formulation (Polysorbate 20 and PEG 300)
* History of seizure disorders unrelated to SCLC brain metastases, or presence of symptomatic brain metastases
* Uncontrolled,intercurrent illness including, but not limited to, symptomatic neurological illness; active, uncontrolled systemic infection considered opportunistic, lifethreatening,or clinically significant at the time of treatment; symptomatic congestive heart failure; unstable angina pectoris; clinically significant cardiac arrhythmia; significant pulmonary disease or hypoxia; or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women and women who are breast feeding;
* human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy

Primary outcomes:
measure: Determine the recommended Phase II dose of obatoclax administered as a 3-hour or 24-hour infusion for 3 consecutive days in Phase I, and response rate in Phase II.
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Clearview Cancer Institute
state: Alabama
city: Muscle Shoals
country: United States
facility: Northwest Alabama Cancer Center
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic-Arizona
state: Arizona
city: Tucson
country: United States
facility: Arizona Clinical Research Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope and Beckman Research Institute
state: California
city: LaJolla
country: United States
facility: University of California-San Diego Moores Cancer Center
state: California
city: Washington
country: United States
facility: Georgetown University Hospital-Lombardi Comprehensive Cancer Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Integrated Community Oncology Network
state: Florida
city: Miami
country: United States
facility: University of Miami-Sylvester Cancer Center
state: Florida
city: New Port Richey
country: United States
facility: Florida Cancer Institute
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Cedar Rapids
country: United States
facility: Iowa Blood and Cancer Center, PLC
state: Iowa
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Louisville
country: United States
facility: James Brown Cancer Center
state: Kentucky
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders
state: Maryland
city: Kalamazoo
country: United States
facility: Kalamazoo Hematology and Oncology
state: Michigan
city: Columbus
country: United States
facility: Mid Ohio Oncology/Hematology, Inc.
state: Ohio
city: Oklahoma City
country: United States
facility: Cancer Care Associates-Oklahoma City
state: Oklahoma
city: Tulsa
country: United States
facility: Cancer Care Associates-Tulsa
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania Abramson Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Greater Philadelphia Cancer and Hematology Specialists
state: Pennsylvania
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas
state: South Carolina
city: Johnson City
country: United States
facility: McLeod Cancer & Blood Center
state: Tennessee
city: Memphis
country: United States
facility: The West Clinic
state: Tennessee
city: Dallas
country: United States
facility: Baylor
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center at Dallas
state: Texas
city: Tyler
country: United States
facility: Tyler Cancer Center
state: Texas
city: Newport News
country: United States
facility: Peninsula Cancer Institute
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Wheeling
country: United States
facility: Wheeling Hospital
state: West Virginia
city: Gabrovo
country: Bulgaria
facility: MHAT "Dr. Tota Venkova"
city: Plovdiv
country: Bulgaria
facility: District Dispensary for Cancer Diseases, Plovdiv
city: Sofia
country: Bulgaria
facility: District Dispensary for Oncology Diseases, Sofia City
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment in Oncology
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Montreal
country: Canada
facility: McGill University
state: Quebec
city: Kladno
country: Czech Republic
facility: Regional Hospital Kladno
city: Kutna Hora
country: Czech Republic
facility: Hospital Kutna Hora
city: Olomouc
country: Czech Republic
facility: University Hospital Olomouc
city: Ostrava-Poruba
country: Czech Republic
facility: Faculty Hospital Ostrava
city: Prague
country: Czech Republic
facility: University Hospital Na Bulovce
city: Budapest
country: Hungary
facility: National Institute of Tuberculosis & Pulmonology
city: Budapest
country: Hungary
facility: Semmelweis University Medical School, Budapest
city: Debrecen
country: Hungary
facility: University Of Debrecen Medical and Health Science Centre
city: Deszk
country: Hungary
facility: Csongrad County Council's Hospital for Chest Diseases
city: Kecskemet
country: Hungary
facility: Bacs-Kiskun County Hospital
city: Matrahaza
country: Hungary
facility: State Hospital Matrahaza
city: Szekszard
country: Hungary
facility: Clinfan Ltd. SMO Tolna County Hospital
city: Torokbalint
country: Hungary
facility: Pest County Hospital
city: Ahmedabad
country: India
facility: Vedanta Institute of Medical Sciences
state: Gujarat
city: Goraj
country: India
facility: Kailash Cancer Hospital and Research Centre
state: Gujarat
city: Bhopal
country: India
facility: Jawaharlal Nehru Cancer Hospital and Research Centre
state: Madhya Pradesh
city: Nashik
country: India
facility: Curie Manavata Cancer Centre
state: Maharashtra
city: Pune
country: India
facility: Noble Hospital
state: Maharashtra
city: Chennai
country: India
facility: Dr. Kamakshi Memorial Hospital
state: Tamal Nadu
city: Ghaziabad
country: India
facility: Galaxy Cancer Institute, Pushpanjali Crosslay Hospital
state: Uttar Pradesh
city: Kolkata
country: India
facility: Orchid Nursing Home
state: West Bengal
city: Bialystok
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im. K. Dluskiego
city: Olsztyn
country: Poland
facility: SPZ Gruzlicy i Chorob Pluc
city: Otwock
country: Poland
facility: Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy
city: Szczecin-Zdunowo
country: Poland
facility: Specjalistyczny Szpital im Prof Alfreda Sokolowskiego
city: Wodzislaw Slaski
country: Poland
facility: Wojewodzki Szpital Chorob Pluc
city: Cluj
country: Romania
facility: Prof. Dr. Ion Chiricuta Oncology Institute Cluj Napoca
city: Iasi
country: Romania
facility: Oncology Medical Centre SCM
city: Oradea
country: Romania
facility: Emergency Clinical County Hospital Oradea
city: Kragujevac
country: Serbia
facility: Center for Pulmonary Diseases, Clinic for Internal Medicine
city: Sremska Kamenica
country: Serbia
facility: Institute for Pulmonary Diseases of Vojvodina
city: Belfast
country: United Kingdom
facility: Northern Ireland Cancer Centre Queens University Belfast
state: Northern Ireland
city: Dorset
country: United Kingdom
facility: Royal Bournemouth Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospital
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
city: Surrey
country: United Kingdom
facility: Royal Surrey County Hospital
Study officials:
affiliation: Gemin X Pharmaceuticals
name: Jean Viallet, MD
role: STUDY_DIRECTOR
References:
citation: Langer CJ, Albert I, Ross HJ, Kovacs P, Blakely LJ, Pajkos G, Somfay A, Zatloukal P, Kazarnowicz A, Moezi MM, Schreeder MT, Schnyder J, Ao-Baslock A, Pathak AK, Berger MS; GEM017 Investigators. Randomized phase II study of carboplatin and etoposide with or without obatoclax mesylate in extensive-stage small cell lung cancer. Lung Cancer. 2014 Sep;85(3):420-8. doi: 10.1016/j.lungcan.2014.05.003. Epub 2014 May 13.