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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01500720
First received: December 22, 2011
Last updated: March 30, 2015
Last verified: March 2015
  Purpose

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)

Condition Intervention Phase
Small Cell Lung Cancer
Drug: Cabazitaxel
Drug: Topotecan
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: Randomization to first tumor progression/clinical deterioration or death (maximum 7.6 months) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: From randomization to date of death (maximum 15 months) ] [ Designated as safety issue: No ]
    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.

  • Progression Free Rate at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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.

  • Overall Objective Tumor Response Rate [ Time Frame: Randomization to disease progression/occurrence (maximum 7.6 months) ] [ Designated as safety issue: No ]
    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.


Enrollment: 179
Study Start Date: March 2012
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cabazitaxel 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.
Other Name: XRP6258
Active Comparator: Topotecan Drug: 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.

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01500720

  Show 58 Study Locations
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01500720     History of Changes
Other Study ID Numbers: ARD12166, 2011-003415-31, U1111-1123-3503
Study First Received: December 22, 2011
Results First Received: March 30, 2015
Last Updated: March 30, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Topotecan
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on July 01, 2015