Trial Outcomes & Findings for Ph I/II Nab-Paclitaxel & Carboplatin w/Concurrent Radiation Therapy for Unresectable Stg III NSCLC (NCT NCT00544648)

Last Updated: 2014-06-09

Results Overview

The highest dose in milligrams per meter of body surface squared (mg/m2) of nab-paclitaxel in combination with carboplatin while maintaining tolerability. Cohorts of 3-6 patients received escalating doses of nab-paclitaxel in combination with carboplatin until the maximum tolerated dose (MTD) was achieved. The MTD is defined as the dose preceding that at which 2 or more of 6 patients experience dose-limiting toxicity (DLT) during the initial cycle of therapy. DLTs per Common Toxicity Criteria v 3.0: recurring non-hematological (except esophagitis) \> Grade 2, non-hematological or esophagitis \> Grade 3 toxicities that are symptomatically unacceptable to patient and result in treatment delay for \> 2 weeks, persistent toxicity resulting in treatment delay for \> 2 weeks.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

13 participants

Primary outcome timeframe

7 weeks

Results posted on

2014-06-09

Participant Flow

Patients were recruited from November 2007 through September 2011

Twenty-two patients signed consent on this study, nine of which were ineligible to receive treatment.

Participant milestones

Participant milestones
Measure	Phase I Nab-paclitaxel in mg/m2 of nab-paclitaxel in combination with carboplatin AUC 2 weekly for 7 weeks with concurrent radiotherapy	Phase II MTD of Nab-paclitaxel in mg/m2 in combination with carboplatin AUC 2 with concurrent radiotherapy weekly for 7 weeks. Responding patients will be treated with consolidation chemotherapy of nab-paclitaxel 100 mg/m2 weekly for 3 weeks every 21 days followed by carboplatin on day 1 of each cycle. One cycle is 21 days. Patients receive 2 cycles of this consolidation chemotherapy.
Overall Study STARTED	11	2
Overall Study COMPLETED	8	1
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I Nab-paclitaxel in mg/m2 of nab-paclitaxel in combination with carboplatin AUC 2 weekly for 7 weeks with concurrent radiotherapy	Phase II MTD of Nab-paclitaxel in mg/m2 in combination with carboplatin AUC 2 with concurrent radiotherapy weekly for 7 weeks. Responding patients will be treated with consolidation chemotherapy of nab-paclitaxel 100 mg/m2 weekly for 3 weeks every 21 days followed by carboplatin on day 1 of each cycle. One cycle is 21 days. Patients receive 2 cycles of this consolidation chemotherapy.
Overall Study Withdrawal by Subject	1	0
Overall Study Adverse Event	1	1
Overall Study progression of disease	1	0

Baseline Characteristics

Ph I/II Nab-Paclitaxel & Carboplatin w/Concurrent Radiation Therapy for Unresectable Stg III NSCLC

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I n=11 Participants Nab-paclitaxel in mg/m2 of nab-paclitaxel in combination with carboplatin AUC 2 weekly for 7 weeks with concurrent radiotherapy	Phase II n=2 Participants MTD of Nab-paclitaxel in mg/m2 in combination with carboplatin AUC 2 with concurrent radiotherapy weekly for 7 weeks. Responding patients will be treated with consolidation chemotherapy of nab-paclitaxel 100 mg/m2 weekly for 3 weeks every 21 days followed by carboplatin on day 1 of each cycle. One cycle is 21 days. Patients receive 2 cycles of this consolidation chemotherapy.	Total n=13 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=93 Participants	2 Participants n=4 Participants	6 Participants n=27 Participants
Age, Categorical >=65 years	7 Participants n=93 Participants	0 Participants n=4 Participants	7 Participants n=27 Participants
Age, Continuous	63 years STANDARD_DEVIATION 9 • n=93 Participants	56 years STANDARD_DEVIATION 4 • n=4 Participants	59 years STANDARD_DEVIATION 16 • n=27 Participants
Sex: Female, Male Female	2 Participants n=93 Participants	1 Participants n=4 Participants	3 Participants n=27 Participants
Sex: Female, Male Male	9 Participants n=93 Participants	1 Participants n=4 Participants	10 Participants n=27 Participants
Region of Enrollment United States	11 participants n=93 Participants	2 participants n=4 Participants	13 participants n=27 Participants

PRIMARY outcome

Timeframe: 7 weeks

Population: MTD based on clinical performance of those patients who received the study drug. One patient withdrew before receiving treatment. No formal statistical analysis, such as hypothesis testing, was performed.

Outcome measures

Outcome measures
Measure	Phase I n=10 Participants Nab-paclitaxel in mg/m2 of nab-paclitaxel in combination with carboplatin AUC 2 weekly for 7 weeks with concurrent radiotherapy
Maximum Tolerated Dose of Nab-paclitaxel When Combined Concurrently With Carboplatin and Radiation (Phase I)	40 mg/m2

PRIMARY outcome

Timeframe: On-study to lesser of date of progression or date of death from any cause (assessed up to 2 years)

Population: All patients are included in the analysis on intention-to-treat basis. Analysis is by Kaplan-Meier method, where either death or progression is an event, with censoring for non-progressed, non-expired patients at greater of off-study date or last known date alive.

Estimated probable duration of life without disease progression, from on-study date to earlier of progression date, or date of death from any cause, using the Kaplan-Meier method with censoring (see Analysis Population Description for additional details). Disease progression is defined by Response Evaluation in Solid Tumors (RECIST) v.1.1: \>= 20% increase in sum of the longest diameter of target lesions, unequivocal progression of non-target lesions, or appearance of new lesions

Outcome measures

Outcome measures
Measure	Phase I n=2 Participants Nab-paclitaxel in mg/m2 of nab-paclitaxel in combination with carboplatin AUC 2 weekly for 7 weeks with concurrent radiotherapy
Progression-free Survival (Phase II)	126 days Interval 126.0 to Upper bound of the 95% confidence interval could not be estimated because of lack of events and patients

SECONDARY outcome

Timeframe: On-study to lesser of date of progression or date of death from any cause (assessed up to 2 years)

Outcome measures

Outcome measures
Measure	Phase I n=11 Participants Nab-paclitaxel in mg/m2 of nab-paclitaxel in combination with carboplatin AUC 2 weekly for 7 weeks with concurrent radiotherapy
Progression-free Survival (Phase I)	231 days Interval 120.0 to 492.0

SECONDARY outcome

Timeframe: On-study date to date of death from any cause (assessed up to 2 years)

Population: All patients are included in the analysis on intention-to-treat basis. Analysis is by Kaplan-Meier method, where death is an event, with censoring for non-expired patients at greater of off-study date or last known alive date.

Estimated probable duration of life from on-study date to date of death from any cause, using Kaplan-Meier method with censoring (see Analysis Population Description for additional details).

Outcome measures

Outcome measures
Measure	Phase I n=11 Participants Nab-paclitaxel in mg/m2 of nab-paclitaxel in combination with carboplatin AUC 2 weekly for 7 weeks with concurrent radiotherapy
Overall Survival (Phase I)	575 days Interval 257.0 to Upper bound of the 95% confidence interval could not be estimated due to lack of events

SECONDARY outcome

Timeframe: On-treatment date to date of progressive disease (assessed up to 2 years)

Population: All patients with best overall response data; patients are excluded if best overall response data is missing (0) or if the patient is non-evaluable for best overall response (n = 1)

Number of patients in each response category, per Response Evaluation in Solid Tumors (RECIST) v.1.1: complete response (CR), disappearance of target lesions; partial response (PR) \>=30% decrease in sum of longest diameter (LD) of target lesions; progressive disease (PD), \>=20% increase in sum of LD of target lesions or appearance of new lesions; stable disease (SD), insufficient change in target lesions or new lesions to qualify as either PD or PR. Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR\>PR\>SD\>PD.

Outcome measures

Outcome measures
Measure	Phase I n=10 Participants Nab-paclitaxel in mg/m2 of nab-paclitaxel in combination with carboplatin AUC 2 weekly for 7 weeks with concurrent radiotherapy
Response (Phase I) Complete response	0 participants
Response (Phase I) Partial response	9 participants
Response (Phase I) Stable disease	1 participants
Response (Phase I) Progressive disease	0 participants

SECONDARY outcome

Timeframe: On-study date to 30 days following final dose of study drug

Population: Total number of patients reported with any toxicity. One patient did not experience toxicity.

Count of patients according to the worst-grade toxicity (WGT) experienced by each, where worst-grade toxicity is per NCI common toxicity criteria: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life-threatening; Grade 5, death.

Outcome measures

Outcome measures
Measure	Phase I n=10 Participants Nab-paclitaxel in mg/m2 of nab-paclitaxel in combination with carboplatin AUC 2 weekly for 7 weeks with concurrent radiotherapy
Number of Patients With Each Worst Grade Toxicity (Phase I) Number of patients with worst Grade 1 toxicity	0 participants
Number of Patients With Each Worst Grade Toxicity (Phase I) Number of patients with worst grade 2 toxicity	2 participants
Number of Patients With Each Worst Grade Toxicity (Phase I) Number of patients with worst grade 3 toxicities	5 participants
Number of Patients With Each Worst Grade Toxicity (Phase I) Number of patients with worst grade 4 toxicity	3 participants
Number of Patients With Each Worst Grade Toxicity (Phase I) Number of patients with worst grade 5 toxicity	0 participants

SECONDARY outcome

Timeframe: Time Frame: date on study to date of death from any cause or last known date alive

Population: Too few patients were enrolled in the Phase II arm for an analysis of overall survival

Estimated probable duration of life from on-study date to date of death from any cause, using Kaplan-Meier method with censoring (see Analysis Population Description for additional details. Too few patients were enrolled in the Phase II arm for an analysis of overall survival

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: at 16 weeks

Population: Treated patients who experienced a toxicity.

The number of patients with worst-grade toxicity at each of five grades following NCI Common Toxicity Criteria: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, disabling, 5 = death

Outcome measures

Outcome measures
Measure	Phase I n=2 Participants Nab-paclitaxel in mg/m2 of nab-paclitaxel in combination with carboplatin AUC 2 weekly for 7 weeks with concurrent radiotherapy
Number of Patients With Each Worst Grade Toxicity (Phase II) Number of patients with worst grade 1 toxicity	0 participants
Number of Patients With Each Worst Grade Toxicity (Phase II) Number of patients with worst grade 2 toxicity	1 participants
Number of Patients With Each Worst Grade Toxicity (Phase II) Number of patients with worst grade 3 toxicity	1 participants
Number of Patients With Each Worst Grade Toxicity (Phase II) Number of patients with worst grade 4 toxicity	0 participants
Number of Patients With Each Worst Grade Toxicity (Phase II) Number of patients with worst grade 5 toxicity	0 participants

SECONDARY outcome

Timeframe: On-treatment date to date of progressive disease (assessed up to 2 years)

Population: All patients with best overall response data; patients are excluded if best overall response data is missing (n = 0) or if the patient is non-evaluable for best overall response (n = 1)

Outcome measures

Outcome measures
Measure	Phase I n=1 Participants Nab-paclitaxel in mg/m2 of nab-paclitaxel in combination with carboplatin AUC 2 weekly for 7 weeks with concurrent radiotherapy
Response (Phase II) Complete response	0 participants
Response (Phase II) Partial response	1 participants
Response (Phase II) Stable disease	0 participants
Response (Phase II) Progressive disease	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: On receipt of tumor tissue blocks

Population: Investigators elected not to perform this analysis.

Secreted protein acidic and rich in cysteine (SPARC) gene expression in tumor specimens.

Outcome measures

Outcome data not reported

Adverse Events

Phase I

Serious events: 5 serious events

Other events: 10 other events

Deaths: 0 deaths

Phase II

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Vicki Keedy, MD

Vanderbilt-Ingram Cancer Center

Phone: 615-936-3524

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Phase I n=10 participants at risk Nab-paclitaxel in mg/m2 in combination with carboplatin AUC 2 with concurrent radiotherapy weekly for 7 weeks. Responding patients will be treated with consolidation chemotherapy of nab-paclitaxel 100 mg/m2 weekly for 3 weeks every 21 days followed by carboplatin on day 1 of each cycle. One cycle is 21 days. Patients receive 2 cycles of this consolidation chemotherapy.	Phase II n=2 participants at risk MTD of Nab-paclitaxel in mg/m2 in combination with carboplatin AUC 2 with concurrent radiotherapy weekly for 7 weeks. Responding patients will be treated with consolidation chemotherapy of nab-paclitaxel 100 mg/m2 weekly for 3 weeks every 21 days followed by carboplatin on day 1 of each cycle. One cycle is 21 days. Patients receive 2 cycles of this consolidation chemotherapy.
Blood and lymphatic system disorders hemoglobin	10.0% 1/10 • Number of events 2 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment	0.00% 0/2 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment
Blood and lymphatic system disorders neutrophils	40.0% 4/10 • Number of events 4 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment	0.00% 0/2 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment
Blood and lymphatic system disorders platelets	30.0% 3/10 • Number of events 3 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment	0.00% 0/2 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment
Skin and subcutaneous tissue disorders radiation dermatitis	10.0% 1/10 • Number of events 1 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment	0.00% 0/2 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment
Metabolism and nutrition disorders hyponatremia	10.0% 1/10 • Number of events 1 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment	0.00% 0/2 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment
Vascular disorders thrombosis	20.0% 2/10 • Number of events 2 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment	0.00% 0/2 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment
Blood and lymphatic system disorders febrile neutropenia	10.0% 1/10 • Number of events 1 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment	0.00% 0/2 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment
Cardiac disorders digoxin toxicity	10.0% 1/10 • Number of events 1 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment	0.00% 0/2 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment
Respiratory, thoracic and mediastinal disorders sore throat	10.0% 1/10 • Number of events 1 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment	0.00% 0/2 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment
General disorders fever in the absence of neutropenia (defined as ANC < 1.0 x 10e9/L)	10.0% 1/10 • Number of events 1 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment	0.00% 0/2 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment
Cardiac disorders hypotension	10.0% 1/10 • Number of events 1 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment	0.00% 0/2 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment
Respiratory, thoracic and mediastinal disorders hypoxia	20.0% 2/10 • Number of events 2 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment	0.00% 0/2 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment
Blood and lymphatic system disorders International Ratio of prothrombin time	10.0% 1/10 • Number of events 1 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment	0.00% 0/2 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment
Nervous system disorders speech impairment	10.0% 1/10 • Number of events 1 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment	0.00% 0/2 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment
Cardiac disorders atrial fibrillation	10.0% 1/10 • Number of events 1 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment	0.00% 0/2 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment
Cardiac disorders sinus tachycardia, probably related to pneumonia	0.00% 0/10 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment	50.0% 1/2 • Number of events 1 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment
General disorders pain-chest, thorax NOS	0.00% 0/10 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment	50.0% 1/2 • Number of events 1 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment
Respiratory, thoracic and mediastinal disorders dyspnea	0.00% 0/10 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment	50.0% 1/2 • Number of events 1 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment
Cardiac disorders tachypnea, probably related to pneumonia	0.00% 0/10 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment	50.0% 1/2 • Number of events 1 • This study began November 2007 through September 2011. Data were collected through April 2013. One patient withdrew before receiving treatment