Study of Palifosfamide-tris in Combination With Carboplatin and Etoposide in Chemotherapy Naïve Patients With Extensive-Stage Small Cell Lung Cancer (The MATISSE Study)

Extensive-Stage Small Cell Lung Cancer Clinical Trial

Official title:

A Multi-center, Open-Label, Adaptive, Randomized Study of Palifosfamide-tris, a Novel DNA Crosslinker, in Combination With Carboplatin and Etoposide (PaCE) Chemotherapy Versus Carboplatin and Etoposide (CE) Alone in Chemotherapy Naïve Patients With Extensive-Stage Small Cell Lung Cancer. The MATISSE Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01555710
• Other study ID #: IPM3002
• Status: Active, not recruiting
• Phase: Phase 3
• First received: March 12, 2012
• Last updated: May 20, 2013
• Start date: May 2012
• Est. completion date: June 2015

Study information

• Verified date: May 2013
• Source: Ziopharm
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review BoardCanada: Health CanadaFrance: Institutional Ethical CommitteeFrance: Ministry of HealthGermany: Ethics CommissionGermany: Ministry of HealthUnited Kingdom: National Institute for Health ResearchUnited Kingdom: Research Ethics CommitteeItaly: Ethics CommitteeItaly: Ministry of HealthUkraine: Ethics CommitteeUkraine: Ministry of HealthSouth Korea: Institutional Review BoardSouth Korea: Korea Food and Drug Administration (KFDA)Russia: Ethics CommitteeRussia: Pharmacological Committee, Ministry of HealthPoland: Ethics CommitteePoland: Ministry of HealthTaiwan : Food and Drug AdministrationTaiwan: Institutional Review BoardIsrael: Ethics CommissionIsrael: Ministry of HealthHungary: Institutional Ethics CommitteeHungary: Ministry of Health, Social and Family Affairs
• Study type: Interventional

Clinical Trial Summary

This is a multinational, multicenter, randomized controlled, open-label, adaptive study to evaluate the efficacy of PaCE chemotherapy in chemotherapy naive subjects with extensive-stage SCLC. Eligible subjects will be stratified according to age, gender, and Eastern Cooperative Oncology Group (ECOG) performance status, and randomized in a 1:1 ratio to receive either PaCE or CE chemotherapy.

The study design uses an adaptive group sequential approach with sample size re-estimation at the interim analysis.

Secondary efficacy endpoints include ORR, PFS, duration of response and changes in QOL and disease-related symptoms. Tumor-related endpoints will be assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines.

The safety of study treatments will be assessed by the frequency and severity of adverse events as determined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03. To provide an initial confirmation of safety, an early interim analysis of safety data only will be performed.

An independent Data Monitoring Committee (DMC) will be convened to assess the safety and efficacy of the study interventions and to monitor the overall conduct of the clinical trial.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 548
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Documented extensive-stage small cell lung cancer.

• Patient has received no prior chemotherapy, adjuvant therapy, or radiotherapy for lung cancer.

• ECOG Performance Status of 0, 1 or 2.

• Adequate bone marrow and organ function based on the results of protocol- specified laboratory tests.

• Male and female patients must agree to use a highly reliable method of birth control during study participation.

• Able to provide informed consent

Exclusion Criteria:

• Previously untreated (non-irradiated), symptomatic brain metastases.

• Known allergy to any of the study drugs or their excipients.

• Any unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a patient and/or their compliance with the protocol, based on screening tests, physical examination and medical history (as specifically defined in the clinical protocol).

• Any malignancy other than small cell lung cancer within the last 5 years prior to randomization, with the exception of cervical carcinoma in situ, nonmelanoma skin cancer, or superficial bladder tumors (Ta, Tis, or T1) that have been successfully and curatively treated with no evidence of recurrent or residual disease. (Exception: Subjects with a history of malignancy other than small cell lung cancer may be enrolled after consultation with the medical monitor provided the patient's prognosis is best defined by the extensive-stage small cell lung cancer).

• Currently pregnant or nursing.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Extensive-Stage Small Cell Lung Cancer
• Lung Neoplasms
• Small Cell Lung Carcinoma

Intervention

Drug:
• Carboplatin
AUC 4 mg/mL/min 1 day every 21 days for a max of 6 cycles.
• Palifosfamide-tris
130 mg/m2/day 3 days every 21 days for a max of 6 cycles.
• Etoposide
100 mg/m2/day 3 days every 21 days for a maximum of 6 cycles.
• Carboplatin
AUC 5 mg/mL/min 1 day every 21 days for a max of 6 cycles.

Locations

Country	Name	City	State
Australia	Southern Medical Day Oncology Care Centre	Wollongong	New South Wales
Canada	R. S. McLaughlin Durham Regional Cancer Center at Lakeridge Health Oshawa	Oshawa	Ontario
Canada	Hôpital Laval	Sainte Foy	Quebec
Canada	CancerCare Manitoba	Winnipeg	Manitoba
France	Centre Hospitalier Universitaire -Hôpital Morvan	Brest	Bretagne
France	Centre François Baclesse	Caen	Basse-normandie
France	Hôpital du Cluzeau	Limoges	Limousin, Lorraine
France	Hôpital Saint Joseph	Marseille	Provence Alpes Cote D'azur
France	Centre Hospitalier Lyon Sud	Pierre Bénité	Rhone-alpes
France	Institut de Cancérologie de l'Ouest - René Gauducheau	Saint Herblain	Pays de La Loire
France	Centre Paul Strauss	Strasbourg
France	Centre Hospitalier Universitaire, Hopital Bretonneau	Tours cedex 1	Centre
Hungary	Debreceni Egyetem Orvos és Egészségtudományi Centrum	Debrecen	Hajdu-bihar
Hungary	Mátrai Gyógyintézet	Mátraháza	Heves
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Medical Organization, Ein Kerem	Jerusalem
Israel	Meir Hospital Sapir Medical Center	Kfar Saba
Israel	Western Gallilee Medical Center	Nahariya
Israel	Rabin Medical Center Beilinson Campus	Petah Tiqwa
Italy	Istituto Nazionale per la Ricerca sul Cancro	Genova
Italy	Azienda Ospedaliera Ospedale Niguarda Ca' Granda	Milano
Italy	Presidio Ospedaliero S. Chiara	Trento
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk	Pomorskie
Poland	Wojewódzkie Centrum Onkologii	Gdansk	Pomorskie
Poland	Specjalistyczny Szpital im. Alfreda Sokolowskiego	Szczecin	Zachodniopomorskie
Poland	Centrum Onkologii - Instytut im. M. Sklodowskiej-Curie w Warszawie	Warszawa	Mazowieckie
Russian Federation	State Institution of Healthcare "Arkhangelsk Regional Clinical Oncology Dispensary"	Arkhangelsk	Primorskiy
Russian Federation	State Budget Institution of Healthcare "Chelyabinsk Regional Clinical Oncology Dispensary"	Chelaybinsk
Russian Federation	Ivanovo Regional Oncology Centre	Ivanovo
Russian Federation	Republican Clinical Oncologic Dispensary of Ministry of health of Republic Tatarstan	Kazan	Tatarstan
Russian Federation	Cancer Research Center n.a. N.N. Blokhin	Moscow
Russian Federation	City Oncology Hospital # 62	Moscow Region	Moscow
Russian Federation	GUZ of Nizhegorodskiy region, Nizhnij Novgorod City Oncology Dispensary	Nizhny Novgorod
Russian Federation	State Educational Institution "S.M. Kirov Military Medical Academy of Ministry of Defense of Russia"	Saint Petersburg
Russian Federation	Saint-Petersburg State Medical University n. a. I. P. Pavlov	Saint-Petersburg
Russian Federation	Republic Clinical Oncology Dispensary of the Ministry of Healthcare of Republic of Bashkortostan	Ufa	Bashkortostan
Russian Federation	State healthcare institution of Yaroslavl region "Regional Clinical Oncologic Hospital"	Yaroslavl
Taiwan	China Medical University Hospital	Taichung
United Kingdom	Wythenshawe Hospital	Manchester	England
United States	New York Oncology Hematology, PC	Albany	New York
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Peachtree Hematology Oncology Consultants	Atlanta	Georgia
United States	Medical Oncology, LLC	Baton Rouge	Louisiana
United States	Birmingham Hematology and Oncology Associates, LLC	Birmingham	Alabama
United States	Montefiore Medical Center	Bronx	New York
United States	Fletcher Allen Health Care	Burlington	Vermont
United States	Charleston Hematology Oncology Associates, PA	Charleston	South Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	The Christ Hospital	Cincinnati	Ohio
United States	Texas Oncology- Baylor, Charles A. Sammons Cancer Center	Dallas	Texas
United States	Texas Oncology-Medical City Dallas	Dallas	Texas
United States	Dayton Cancer Center, Medical Oncology Hematology Associates	Dayton	Ohio
United States	Saint Mary's Medical Center	Duluth	Minnesota
United States	Fairfax Northern Virginia Hematology-Oncology, PC	Fairfax	Virginia
United States	Central Indiana Cancer Centers	Fishers	Indiana
United States	Frederick Memorial Hospital Regional Cancer Therapy Center	Frederick	Maryland
United States	Medical and Surgical Specialists, LLC	Galesburg	Illinois
United States	University of Texas Medical Branch at Galveston	Galveston	Texas
United States	Goshen Center for Cancer Care	Goshen	Indiana
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	Oncology Consultants, PA	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Baptist Cancer Institute	Jacksonville	Florida
United States	Medical Oncology Associates Of Wyoming Valley, PC	Kingston	Pennsylvania
United States	Horizon Oncology Center	Lafayette	Indiana
United States	Central Baptist Hospital	Lexington	Kentucky
United States	University of Southern California	Los Angeles	California
United States	Wisconsin Institutes for Medical Research	Madison	Wisconsin
United States	Virginia Piper Cancer Institute	Minneapolis	Minnesota
United States	Hematology Oncology Associates of Northern New Jersey, PA, Carol G. Simon Cancer Center	Morristown	New Jersey
United States	Indiana University Health Ball Memorial Hospital	Muncie	Indiana
United States	Christiana Care Health Services	Newark	Delaware
United States	Illinois Cancer Specialists	Niles	Illinois
United States	University of Kansas Hospital	Overland Park	Kansas
United States	Hematology Oncology Associates of the Treasure Coast	Port Sant Lucie	Florida
United States	Redwood Regional Oncology Group	Santa Rosa	California
United States	Swedish Medical Center	Seattle	Washington
United States	Texas Oncology, PA	Wichita Falls	Texas
United States	Metro Health Cancer Center	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Ziopharm

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Hungary,  Israel,  Italy,  Poland,  Russian Federation,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)		Assessed every 12 weeks for survival until 1 year following completion of enrollment	No
Secondary	Progression Free Survival (PFS)		Assessed every 6 weeks for 22 weeks, then every 12 weeks until progressive disease, initiation of alternate anticancer therapy, or 1 year following the last patient enrolled (whichever is soonest)	No
Secondary	Quality of Life (QOL) as assessed by EQ-5D-3L and QLQ-LC13		Assessed every 3 weeks for 22 weeks, then every 12 weeks until 1 year following the last patient enrolled	No
Secondary	Objective Response Rate (ORR)		Assessed every 6 weeks for 22 weeks, then every 12 weeks until a partial or complete response is confirmed	No
Secondary	Response Duration		Time from the date of first objective response (partial or complete response), with subsequent confirmation, until the date of disease progression or the occurrence of death	No
Secondary	Safety parameters (number of adverse events as well as number of findings from physical examinations, ECGs, vital signs, and clinical laboratory results)using NCI CTCAE v. 4.03		22 weeks	No