Cabazitaxel Compared to Topotecan for the Treatment of Small Cell Lung Cancer

Small Cell Lung Cancer Clinical Trial

Official title:

Randomized Phase II Study of Cabazitaxel Versus Topotecan in Small Cell Lung Cancer Patients With Progressive Disease During or After a First Line Platinum Based Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01500720
• Other study ID #: ARD12166
• Secondary ID: 2011-003415-31U1
• Status: Completed
• Phase: Phase 2
• First received: December 22, 2011
• Last updated: March 30, 2015
• Start date: March 2012
• Est. completion date: April 2014

Study information

• Verified date: March 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

To demonstrate progression free survival (PFS) improvement for cabazitaxel compared to topotecan in participants with sensitive or resistant/refractory small cell lung cancer following a first line platinum based chemotherapy.

Secondary Objectives:

• To assess disease progression free rate at 12 weeks

• To assess Response Rate (Response Evaluation Criteria in Solid Tumor [RECIST] 1.1) and duration of response

• To assess Overall Survival (OS)

• To assess the Safety (National Cancer Institute - Common Toxicity Criteria [NCI-CTC] version 4.03)

• To assess the Health-Related Quality of Life (HRQoL)

Description:

Participants are to be treated until progressive disease, unacceptable toxicity or refusal for further study treatment.

All participants are to be followed for disease progression documentation and for participant status until the study cut-off date.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 179
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria :

• Histological/cytological proven locally advanced or metastatic small cell lung cancer with progressive disease during or after first line platinum based chemotherapy

• Male or female greater than or equal to (>=) 18 years (or country's legal age of majority if greater than [>]18 years)

• Participants with measurable disease, Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1)

• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (<=) 1

Exclusion criteria:

• Absence of signed and dated Institutional Review Board (IRB)-approved participant informed consent form prior to enrollment into the study

• More than one prior chemotherapy regimen. Prior treatment with topotecan or taxanes

• Less than 28 days elapsed from prior treatment with chemotherapy, radiotherapy or surgery to the time of randomization (Radiotherapy for bone pain palliation is allowed)

• Adverse events (excluding alopecia) from any prior anticancer therapy of grade >1 (National Cancer Institute Common Terminology Criteria [NCI CTCAE] v4.03) at the time of randomization

• Uncontrolled Central Nervous System (CNS) metastases: participants with CNS metastases may have previous irradiation, only participants with stable disease or response to irradiation who are without CNS symptoms and on a maximum steroid dose of dexamethasone 8 mg daily or equivalent could be included

• Participants with known leptomeningeal metastases

• History of other, invasive neoplasm requiring ongoing therapy

• Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to randomization

• Any of the following within 6 months prior to study enrollment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association class III or IV congestive heart failure, stroke or transient ischemic attack

• Any severe acute or chronic medical condition, which could impair the ability of the participant to participate in the study or interfere with interpretation of study results

• Known Human Immunodeficiency Virus (HIV) disease, or active hepatitis B or C (systematic testing was not required)

• Pregnant or breast-feeding woman. Positive serum or urine pregnancy test prior to randomization

• Participant with reproductive potential (M/F) who did not agree to use an accepted and effective method of contraception during the study treatment period and for at least 6 months after the completion of the study treatment. The definition of "effective method of contraception" was based on the investigator's judgment. Effective method of contraception should also be adapted to local regulation

• History of hypersensitivity to polysorbate 80

• Inadequate organ and bone marrow function as evidenced by:

• Hemoglobin less than [<] 9.0 gram per deciliter (g/dL)

• Absolute neutrophil count <1.5 x 10^9 per liter

• Platelet count <100 x 10^9 per liter

• Aspartate Aminotransferase/Serum Glutamic Oxaloacetic Transaminase (AST/SGOT) and/or alanine aminotransferase/Serum Glutamic-Pyruvic Transaminase (ALT/SGPT) >2.5 x Upper Limit of Normal (ULN)

• Alkaline Phosphatase (AP) >2.5 x ULN. In case of liver metastases AP >5 x ULN

• Total bilirubin >1.0 x ULN

• Serum Creatinine >1.5 x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated according to Chronic Kidney Disease Epidemiology Collaboration formula, and creatinine clearance <60 milliliter per minute (mL/min) was exclude the participant.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Design

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

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Drug:
• Cabazitaxel
Cabazitaxel 25 milligram per square meter (mg/m^2) intravenously (IV) on Day 1 every 3 weeks (21-day cycle) until unacceptable toxicity, disease progression or withdrawal consent.
• Topotecan
Topotecan 1.5 mg/m^2 IV on Day 1 to Day 5 every 3 weeks (21-Day cycle) until unacceptable toxicity, disease progression or withdrawal consent.

Locations

Country	Name	City	State
Brazil	Investigational Site Number 076001	Porto Alegre
Canada	Investigational Site Number 124003	Montreal
Canada	Investigational Site Number 124002	Oshawa
Canada	Investigational Site Number 124004	Rimouski
Canada	Investigational Site Number 124001	Toronto
Chile	Investigational Site Number 152001	Santiago
Chile	Investigational Site Number 152005	Santiago
France	Investigational Site Number 250005	Brest
France	Investigational Site Number 250004	Caen Cedex
France	Investigational Site Number 250006	La Tronche
France	Investigational Site Number 250002	Lille
France	Investigational Site Number 250003	Saint-Herblain Cedex
France	Investigational Site Number 250007	Villejuif Cedex
Germany	Investigational Site Number 276003	Großhansdorf
Germany	Investigational Site Number 276006	Löwenstein
Greece	Investigational Site Number 300003	Athens
Greece	Investigational Site Number 300005	Athens
Greece	Investigational Site Number 300001	Heraklion
Greece	Investigational Site Number 300002	Thessaloniki
Greece	Investigational Site Number 300004	Thessaloniki
Hungary	Investigational Site Number 348001	Budapest
Hungary	Investigational Site Number 348002	Budapest
Hungary	Investigational Site Number 348004	Budapest
Hungary	Investigational Site Number 348003	Törökbálint
Italy	Investigational Site Number 380001	Genova
Italy	Investigational Site Number 380002	Livorno
Italy	Investigational Site Number 380005	Novara
Italy	Investigational Site Number 380004	Parma
Korea, Republic of	Investigational Site Number 410001	Seoul
Korea, Republic of	Investigational Site Number 410002	Seoul
Korea, Republic of	Investigational Site Number 410003	Seoul
Norway	Investigational Site Number 578001	Oslo
Norway	Investigational Site Number 578003	Stavanger
Norway	Investigational Site Number 578002	Trondheim
Poland	Investigational Site Number 616004	Gdansk
Poland	Investigational Site Number 616003	Lublin
Poland	Investigational Site Number 616002	Poznan
Poland	Investigational Site Number 616001	Warszawa
Romania	Investigational Site Number 642003	Cluj Napoca
Romania	Investigational Site Number 642005	Cluj-Napoca
Romania	Investigational Site Number 642001	Craiova
Romania	Investigational Site Number 642002	Timisoara
Russian Federation	Investigational Site Number 643001	Moscow
Russian Federation	Investigational Site Number 643005	St-Petersburg
Russian Federation	Investigational Site Number 643006	Tula
Russian Federation	Investigational Site Number 643003	Yaroslavl
Spain	Investigational Site Number 724002	Badalona
Spain	Investigational Site Number 724004	Barcelona
Spain	Investigational Site Number 724005	Málaga
Spain	Investigational Site Number 724001	Valencia
Ukraine	Investigational Site Number 804002	Dnipropetrovsk
Ukraine	Investigational Site Number 804004	Donetsk
Ukraine	Investigational Site Number 804001	Lviv
United States	Investigational Site Number 840006	Lebanon	New Hampshire
United States	Investigational Site Number 840003	Middletown	Ohio
United States	Investigational Site Number 840007	Muscle Shoals	Alabama
United States	Investigational Site Number 840005	Omaha	Nebraska
United States	Investigational Site Number 840001	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  Chile,  France,  Germany,  Greece,  Hungary,  Italy,  Korea, Republic of,  Norway,  Poland,  Romania,  Russian Federation,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	PFS was defined as the time interval from the date of randomization to the date of occurrence of the first documented tumor progression or death due to any cause, whichever came first. Median PFS was estimated using the Kaplan-Meier method. Progression was defined using Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study or unequivocal progression of existing non-target lesion. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The appearance of one or more new lesions is also considered progression.	Randomization to first tumor progression/clinical deterioration or death (maximum 7.6 months)	No
Secondary	Overall Survival	Overall survival was defined as the time interval from the date of randomization to the date of death due to any cause. In the absence of confirmation of death, survival time was to be censored at the last date the participant was known to be alive. Median time was estimated by Kaplan-Meier curve.	From randomization to date of death (maximum 15 months)	No
Secondary	Progression Free Rate at Week 12	Progression was defined using Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study or unequivocal progression of existing non-target lesion. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. Death due to disease progression within 12 weeks without radiological documentation of progressive disease was counted as an event. Percentage of participants who were progression free at week 12 are reported.	Week 12	No
Secondary	Overall Objective Tumor Response Rate	Overall objective tumor response was defined as the proportion of participants with confirmed RECIST 1.1 achieving a complete response (CR) or partial response (PR). CR was defined as disappearance of all target/non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Percentage of participants with overall objective tumor response is reported.	Randomization to disease progression/occurrence (maximum 7.6 months)	No