Phase II Study of Cabazitaxel-XRP6258 in Advanced Non-Small Cell Lung Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University of Alabama at Birmingham
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Francisco Robert,MD, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT01438307
First received: September 15, 2011
Last updated: January 16, 2014
Last verified: January 2014
  Purpose

Lung cancer is the leading cause of cancer death worldwide and in the United States. The majority of lung cancers are non-small cell lung cancer (NSCLC). The majority of NSCLC cases are advanced at the time of diagnosis. Chemotherapy has improved overall survival but remains limited at < 12 months median overall survival. New approaches are needed for second line chemotherapy treatment. Cabazitaxel-XRP6258 has shown increased overall survival in metastatic prostate cancer and it is hopeful it can do the same in advanced NSCLC.


Condition Intervention Phase
Non-small Cell Lung Cancer (NSCLC)
Stage IV NSCLC
Metastatic NSCLC
Drug: Cabazitaxel-XRP6258
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of a Novel Taxane (Cabazitaxel-XRP6258) in Previously Treated Advanced Non-Small Cell Lung Cancer (NSCLC) Patients

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • Second line treatment objective response rate [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Subjects who have failed first line chemotherapy for Stage IV NSCLC will be assessed for this second line treatment with Cabazitaxel-XRP6528. The primary objective is to show an objective response rate of greater than or equal to 15% for the second line treatment.


Secondary Outcome Measures:
  • Time to progression [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Assessment will be made on subjects with Stage IV NSCLC who receive Cabazitaxel-XRP6258 after progressing with first line platinum-based chemotherapy.

  • Safety in subjects with Stage IV NSCLC who received Cabazitaxel-XRP6258 [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    Assessment will be made in subjects after progressing with first line platinum-based chemotherapy. Safety will be assessed using the NCI common toxicity criteria (Version 4.0).

  • Progression free survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Assessment will be made in subjects with Stage IV NSCLC who receive Cabazitaxel-SRP6258 after progressing with first line platinum-based chemotherapy.

  • Overall survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Assessment will be made in subjects with Stage IV NSCLC who receive Cabazitaxel-SRP6258 after progressing with first line platinum-based chemotherapy.

  • Time to progression in a subset of subjects [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    The subset of subjects to be assessed have Stage IV NSCLC and asymptomatic brain metastases.

  • Safety in a subset of subjects [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    The subset of subjects to be assessed have Stage IV NSCLC and asymptomatic brain metastases. Safety will be assessed using the NCI common toxicity criteria (Version 4.0)in addition to an MRI of the brain after every other chemotherapy cycle or at any time there is new neurological symptoms.

  • Response rate in a subset of subjects [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    The subset of subjects to be assessed have Stage IV NSCLC and asymptomatic brain metastases.

  • Overall survival in a subset of patients [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    The subset of subjects to be assessed have Stage IV NSCLC and asymptomatic brain metastases.

  • Exploratory laboratory correlation of MDR 1p-glycoprotein as to the response rate [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Demographic and baseline laboratory results will be summarized using descriptive statistics such as mean, median and frequencies. Duration of response, time to progression and overall survival will be calculated using Kaplan Meier, along with two-sided 95% confidence levels.

  • Exploratory laboratory correlation of MDR 1p-glycoprotein as to the time to progression [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Demographic and baseline laboratory results will be summarized using descriptive statistics such as mean, median and frequencies. Duration of response, time to progression and overall survival will be calculated using Kaplan Meier, along with two-sided 95% confidence levels.

  • Exploratory laboratory correlation of MDR 1p-glycoprotein as to the overall survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Demographic and baseline laboratory results will be summarized using descriptive statistics such as mean, median and frequencies. Duration of response, time to progression and overall survival will be calculated using Kaplan Meier, along with two-sided 95% confidence levels.

  • Exploratory laboratory correlation of MRP3 as to the response rate [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Demographic and baseline laboratory results will be summarized using descriptive statistics such as mean, median and frequencies. Duration of response, time to progression and overall survival will be calculated using Kaplan Meier, along with two-sided 95% confidence levels.

  • Exploratory laboratory correlation of MRP3 as to the time to progression [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Demographic and baseline laboratory results will be summarized using descriptive statistics such as mean, median and frequencies. Duration of response, time to progression and overall survival will be calculated using Kaplan Meier, along with two-sided 95% confidence levels.

  • Exploratory laboratory correlation of MRP3 as to the overall survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Demographic and baseline laboratory results will be summarized using descriptive statistics such as mean, median and frequencies. Duration of response, time to progression and overall survival will be calculated using Kaplan Meier, along with two-sided 95% confidence levels.


Estimated Enrollment: 96
Study Start Date: September 2011
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Schedule A

Subjects with advanced non-small cell lung cancer who have been previously treated will be given a specific regimen of the novel taxane, Cabazitaxel-XRP6258.

Subjects with asymptomatic brain metastases will be eligible for the study and a subset analysis will take place to help determine what, if any, effect Cabazitaxel-XRP6258 has on brain metastases.

Drug: Cabazitaxel-XRP6258
Subjects in Schedule A will begin with an initial dose of 20 mg/m2 every 3 weeks as a 1 hour IV infusion. If no dose limiting toxicities are experienced after cycle 1, then the dose will be escalated to 25 mg/m2. Treatment with Cabazitaxel-XRP6258 will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity or withdrawal of consent. Further treatment after 6 cycles of treatment in patients who achieved an objective response or stable disease, and no significant toxicity will be an individual decision from the investigator.
Experimental: Schedule B

Subjects with advanced non-small cell lung cancer who have been previously treated will be given a specific regimen of the novel taxane, Cabazitaxel-XRP6258, different from Schedule A.

Subjects with asymptomatic brain metastases will be eligible for the study and a subset analysis will take place to help determine what, if any, effect Cabazitaxel-XRP6258 has on brain metastases.

Drug: Cabazitaxel-XRP6258
Subjects in Schedule B will begin with an initial dose of 8.4 mg/m2 as a 1 hour IV infusion on days 1, 8, 15, and 22 of a 5-week cycle. If no dose limiting toxicities are experienced after cycle 1, then the dose will be escalated to 10 mg/m2. Treatment with Cabazitaxel-XRP6258 will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity or withdrawal of consent. Further treatment after 6 cycles of treatment in patients who achieved an objective response or stable disease, and no significant toxicity will be an individual decision from the investigator.

Detailed Description:

A substantial number of patients with lung cancer progress after first line treatment and require second line chemotherapy. Lung cancer appears to account for 40-50% of all known brain metastasis. The incidence of brain metastases among lung cancer patients ranges from 16-20%. Chemotherapy has had limited utility due to problems crossing the blood brain barrier.

Currently there are three drugs approved by the FDA for second line treatment of NSCLC but each has distinct toxicities. Cabazitaxel-XRP6258 is a potent novel taxane with enhanced activity against an increased number of cell lines including lung, prostate, colon, pancreas, head and neck, kidney, gastric, glioblastoma, and melanoma. It also has the ability to cross the blood brain barrier. Cabazitaxel-XRP6258 was found to have an improved antiproliferative activity than other chemotherapy agents against insensitive cell lines. The Phase I studies of Cabazitaxel-SRP6258 have determined dosage and schedule recommendations in advanced NSCLC patients to be utilized for a Phase II multicenter study.

Subjects will be placed on one of two schedules (A or B) each with a specified dosage and administration schedule. All subjects will be followed for survival/progression after every 2 cycles of therapy with imaging studies. A two stage design will be used for each of the two schedules. Fourteen subjects will be accrued for each schedule in the first stage with possible accrual of an additional 34 subjects per schedule depending upon the first stage results.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologic or cytologic diagnosis of NSCLC (squamous or non-squamous or NSCLC-not specified)
  • Subjects who have failed first line chemotherapy (platinum doublets or non- platinum doublets [previous taxane exposure is allowed]) for Stage IV NSCLC.
  • Measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Age > 18 years old
  • Adequate bone marrow, liver and renal function, defined as:

    • Absolute neutrophil count (ANC) greater than or equal to 1500/ul
    • Hemoglobin greater than or equal to 10 g/dl
    • Platelet count greater than or equal to 100,000/ul
    • Total bilirubin less than or equal to 1.5 x upper limit of normal (except in subjects with documented Gilbert's syndrome)
    • AST/ALT less than or equal to 1.5 x upper limit of normal
    • Serum creatinine less than or equal to 1.8 mg/dl
  • Fully recovered from any previous surgery (at least 4 weeks since major surgery)
  • Fully recovered from previous radiation therapy (at least 2 weeks)
  • All subjects must agree to practice approved methods of birth control (if applicable). A negative pregnancy test must be documented during the screening period for women of childbearing potential.
  • Written informed consent and authorization to use and disclose health information (HIPAA) must be signed by the subject.
  • Subjects with symptomatic brain metastases should be adequately treated and controlled prior to the initiation of the study. Subjects with asymptomatic brain metastases will be allowed in the study without any prior therapy for brain metastases.

Exclusion Criteria:

  • Concurrent cancer chemotherapy, biologic therapy or radiotherapy
  • Administration of any investigational agent within 28 days prior to administration of current therapy
  • Untreated symptomatic brain metastases
  • Greater than or equal to Grade 2 neuropathy
  • Concurrent serious infection
  • Concomitant severe or uncontrolled underlying medical disease unrelated to the tumor, which is likely to compromise subject safety and affect the outcome of the study.
  • Treatment for a cancer other the NSCLC within 5 years prior to enrollment, with the exception of basal cell carcinoma or carcinoma in situ of the cervix
  • Any evidence of history of hypersensitivity for the taxane class of chemotherapy drugs
  • History of positive serology for HIV
  • Psychiatric disorder that prevents subjects from providing informed consent or following protocol instructions
  • Pregnant or lactating women
  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: NCT01438307

Contacts
Contact: Mary S. Jerome, RN, BSN, OCN 205-934-5092 msjerome@uab.edu
Contact: Pam Dixon, RN, BSN, OCN, CCRP 205-975-5387 pamdixon@uab.edu

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Principal Investigator: Francisco Robert, MD         
United States, Georgia
Georgia Cancer Center Recruiting
Atlanta, Georgia, United States, 30060
Contact: Roldolfo Bordoni, MD    770-590-8311    Roldolfo.Bordoni@gacancer.com   
Contact: Pam Dixon, RN, BSN, OCN, CCRP    205-975-5387    pamdixon@uab.edu   
Principal Investigator: Roldolfo Bordoni, MD         
Sponsors and Collaborators
University of Alabama at Birmingham
Sanofi
Investigators
Principal Investigator: Francisco Robert, MD University of Alabama at Birmingham
  More Information

No publications provided

Responsible Party: Francisco Robert,MD, Professor, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT01438307     History of Changes
Other Study ID Numbers: F110512012 (UAB 1021), UAB 1021
Study First Received: September 15, 2011
Last Updated: January 16, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Alabama at Birmingham:
Non-small cell lung cancer
Cabazitaxel-XRP6258
P-glycoprotein
taxane
Advanced NSCLC

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on July 31, 2014