Trial Outcomes & Findings for Phase II Study of Cabazitaxel-XRP6258 in Advanced Non-Small Cell Lung Cancer (NCT NCT01438307)

NCT ID: NCT01438307

Last Updated: 2017-05-24

Results Overview

The objective response is defined as the percentage of patients that achieve a complete and/or partial response according to The Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 28 participants
• Primary outcome timeframe: Baseline up to 28 months
• Results posted on: 2017-05-24

Participant Flow

Subjects will be randomized to one of two schedules (A or B) each with a specified dosage and administration schedule. A two stage design will be used for each of the two schedules. Fourteen subjects will be accrued for each schedule in Stage I with an additional 34 subjects in Stage II per schedule depending upon the first stage results.

New approaches are needed for 2nd line chemotherapy treatment. Cabazitaxel-XRP6258 has shown increased overall survival in metastatic prostate cancer and it is hopeful to do the same in advanced Non-Small Cell Lung Cancer (NSCLC).This phase II study will evaluate the efficacy of cabazitaxel chemotherapy in 2nd line setting in patients with NSCLC.

Participant milestones

Measure	Treatment Schedule A Cabazitaxel 20 mg/m2 every 3 weeks as a 1 hour IV infusion with a planned dose escalation of to 25 mg/m2 if no dose limiting toxicities (DLTs) were observed. All subjects will be followed for survival/progression after every 2 cycles of therapy with imaging studies.	Treatment Schedule B Cabazitaxel 8.4 mg/m2 weekly on Days 1, 85, 15, and 22 of a 5 week cycle with a planned dose escalation to 10 mg/m2 weekly if no dose limiting toxicities (DLTs) were observed. All subjects will be followed for survival/progression after every 2 cycles of therapy with imaging studies.
Overall Study STARTED	14	14
Overall Study COMPLETED	13	13
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Measure	Treatment Schedule A Cabazitaxel 20 mg/m2 every 3 weeks as a 1 hour IV infusion with a planned dose escalation of to 25 mg/m2 if no dose limiting toxicities (DLTs) were observed. All subjects will be followed for survival/progression after every 2 cycles of therapy with imaging studies.	Treatment Schedule B Cabazitaxel 8.4 mg/m2 weekly on Days 1, 85, 15, and 22 of a 5 week cycle with a planned dose escalation to 10 mg/m2 weekly if no dose limiting toxicities (DLTs) were observed. All subjects will be followed for survival/progression after every 2 cycles of therapy with imaging studies.
Overall Study Death	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Schedule A n=14 Participants Cabazitaxel 20 mg/m2 every 3 weeks as a 1 hour IV infusion with a planned dose escalation of to 25 mg/m2 if no dose limiting toxicities (DLTs) were observed.	Schedule B n=14 Participants Cabazitaxel 8.4 mg/m2 weekly on Days 1, 85, 15, and 22 of a 5 week cycle with a planned dose escalation to 10 mg/m2 weekly if no dose limiting toxicities (DLTs) were observed.	Total n=28 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants	10 Participants n=7 Participants	15 Participants n=5 Participants
Age, Categorical >=65 years	9 Participants n=5 Participants	4 Participants n=7 Participants	13 Participants n=5 Participants
Age, Continuous	68 Years n=5 Participants	64 Years n=7 Participants	65 Years n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment United States	14 participants n=5 Participants	14 participants n=7 Participants	28 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to 28 months

The objective response is defined as the percentage of patients that achieve a complete and/or partial response according to The Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1).

Outcome measures

Measure	Schedule A n=13 Participants 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. 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.	Schedule B n=13 Participants Subjects with advanced NSCLC 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. 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 de
Objective Response Rate	0 participants	1 participants

SECONDARY outcome

Timeframe: Baseline up to 28 months

Progression Free Survival is defined from the initiation of treatment until radiological-clinical evidence of progression according to the RECIST (v 1.1).

Outcome measures

Measure	Schedule A n=13 Participants 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. 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.	Schedule B n=13 Participants Subjects with advanced NSCLC 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. 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 de
Progression Free Survival	3 months Interval 1.0 to 5.0	3 months Interval 2.0 to 3.0

SECONDARY outcome

Timeframe: Baseline up to 28 months

Population: 14 patients in each cohort were included in the toxicity assessment and 13 patients in each cohort in the efficacy assessment.

Safety will be assessed using the National Cancer Institute Common Toxicity Criteria (Version 4.0) and all adverse events will be recorded prior to each treatment regimen.

Outcome measures

Measure	Schedule A n=14 Participants 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. 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.	Schedule B n=14 Participants Subjects with advanced NSCLC 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. 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 de
Number of Patients With Any Graded Adverse Event	14 Participants	14 Participants

SECONDARY outcome

Timeframe: 28 months

Assessment will be made in subjects with Stage IV NSCLC who receive Cabazitaxel-SRP6258 after progressing with first line platinum-based chemotherapy.

Outcome measures

Measure	Schedule A n=13 Participants 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. 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.	Schedule B n=13 Participants Subjects with advanced NSCLC 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. 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 de
Overall Survival	6 months Interval 0.5 to 7.0	13 months Interval 0.5 to 14.0

Adverse Events

Treatment Schedule A

Serious events: 7 serious events

Other events: 5 other events

Deaths: 1 deaths

Treatment Schedule B

Serious events: 1 serious events

Other events: 6 other events

Deaths: 1 deaths

Serious adverse events

Measure	Treatment Schedule A n=14 participants at risk Cabazitaxel 20 mg/m2 every 3 weeks as a 1 hour IV infusion with a planned dose escalation of to 25 mg/m2 if no dose limiting toxicities (DLTs) were observed. All subjects will be followed for survival/progression after every 2 cycles of therapy with imaging studies.	Treatment Schedule B n=14 participants at risk Cabazitaxel 8.4 mg/m2 weekly on Days 1, 85, 15, and 22 of a 5 week cycle with a planned dose escalation to 10 mg/m2 weekly if no dose limiting toxicities (DLTs) were observed. All subjects will be followed for survival/progression after every 2 cycles of therapy with imaging studies.
Blood and lymphatic system disorders Neutropenia	42.9% 6/14 • Number of events 6 • 28 Months	0.00% 0/14 • 28 Months
Blood and lymphatic system disorders Febrile Neutropenia	28.6% 4/14 • Number of events 4 • 28 Months	7.1% 1/14 • Number of events 1 • 28 Months
Renal and urinary disorders Hematuria	14.3% 2/14 • Number of events 2 • 28 Months	0.00% 0/14 • 28 Months
Respiratory, thoracic and mediastinal disorders Dyspnea	7.1% 1/14 • Number of events 1 • 28 Months	7.1% 1/14 • Number of events 3 • 28 Months

Other adverse events

Measure	Treatment Schedule A n=14 participants at risk Cabazitaxel 20 mg/m2 every 3 weeks as a 1 hour IV infusion with a planned dose escalation of to 25 mg/m2 if no dose limiting toxicities (DLTs) were observed. All subjects will be followed for survival/progression after every 2 cycles of therapy with imaging studies.	Treatment Schedule B n=14 participants at risk Cabazitaxel 8.4 mg/m2 weekly on Days 1, 85, 15, and 22 of a 5 week cycle with a planned dose escalation to 10 mg/m2 weekly if no dose limiting toxicities (DLTs) were observed. All subjects will be followed for survival/progression after every 2 cycles of therapy with imaging studies.
Nervous system disorders Neuropathy	35.7% 5/14 • Number of events 5 • 28 Months	42.9% 6/14 • Number of events 6 • 28 Months

Additional Information

Francisco Robert, MD

UAB

Phone: 205-934-5077

Email: paco@uab.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place