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

Non-small Cell Lung Cancer (NSCLC) Clinical Trial

Official title:

Phase II Study of a Novel Taxane (Cabazitaxel-XRP6258) in Previously Treated Advanced Non-Small Cell Lung Cancer (NSCLC) Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01438307
• Other study ID #: F110512012 (UAB 1021)
• Secondary ID: UAB 1021
• Status: Completed
• Phase: Phase 2
• First received: September 15, 2011
• Last updated: January 8, 2016
• Start date: September 2011
• Est. completion date: September 2015

Study information

• Verified date: January 2016
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: September 2015
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Metastatic NSCLC
• Non-small Cell Lung Cancer (NSCLC)
• Stage IV NSCLC

Intervention

Drug:
• Cabazitaxel-XRP6258 (3-week cycle)
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.
• Cabazitaxel-XRP6258 (5-week cycle)
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.

Locations

Country	Name	City	State
United States	Georgia Cancer Center	Atlanta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama

Sponsors (2)

Lead Sponsor	Collaborator
University of Alabama at Birmingham	Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Second line treatment objective response rate	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.	24 months	No
Secondary	Time to progression	Assessment will be made on subjects with Stage IV NSCLC who receive Cabazitaxel-XRP6258 after progressing with first line platinum-based chemotherapy.	24 months	No
Secondary	Safety in subjects with Stage IV NSCLC who received Cabazitaxel-XRP6258	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).	24 months	Yes
Secondary	Progression free survival	Assessment will be made in subjects with Stage IV NSCLC who receive Cabazitaxel-SRP6258 after progressing with first line platinum-based chemotherapy.	24 months	No
Secondary	Overall survival	Assessment will be made in subjects with Stage IV NSCLC who receive Cabazitaxel-SRP6258 after progressing with first line platinum-based chemotherapy.	24 months	No
Secondary	Time to progression in a subset of subjects	The subset of subjects to be assessed have Stage IV NSCLC and asymptomatic brain metastases.	24 months	No
Secondary	Safety in a subset of subjects	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.	24 months	Yes
Secondary	Response rate in a subset of subjects	The subset of subjects to be assessed have Stage IV NSCLC and asymptomatic brain metastases.	24 months	Yes
Secondary	Overall survival in a subset of patients	The subset of subjects to be assessed have Stage IV NSCLC and asymptomatic brain metastases.	24 months	No
Secondary	Exploratory laboratory correlation of MDR 1p-glycoprotein as to the response rate	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.	24 months	No
Secondary	Exploratory laboratory correlation of MDR 1p-glycoprotein as to the time to progression	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.	24 months	No
Secondary	Exploratory laboratory correlation of MDR 1p-glycoprotein as to the overall survival	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.	24 months	No
Secondary	Exploratory laboratory correlation of MRP3 as to the response rate	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.	24 months	No
Secondary	Exploratory laboratory correlation of MRP3 as to the time to progression	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.	24 months	No
Secondary	Exploratory laboratory correlation of MRP3 as to the overall survival	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.	24 months	No