Trial Outcomes & Findings for Pulsed Paclitaxel And Daily Thoracic Radiotherapy For Inoperable (Stage I/II) Or Unresectable Lung Cancer (NCT NCT00178256)

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

41 participants

Primary outcome timeframe

5 years

Results posted on

2015-08-21

Participant Flow

Participant milestones

Participant milestones
Measure	First Dose Cohort (15mg/m2 Taxol) MWF and Daily RT On Mondays, Wednesdays, and Fridays, paclitaxel infusion will given. On Monday, Tuesday, Wednesday, Thursday, Friday Thoracic XRT will be given. A minimum of three patients will be assigned at each dose level. If no DLTs are observed then the next three patients enrolled will receive a dose of 5 mg/m2 per dose more than the previous group. If one or two instances of DLT are observed then an additional three patients will be tested at the same dose. If DLT is observed in at most two of six patients then dose escalation will continue in the next three patients enrolled. Dose-limiting toxicity (DLT) is defined as grade 4 hematologic toxicity, or grade 3 and 4 non-hematologic toxicity excluding nausea and vomiting according to RTOG and Cooperative Group common toxicity criteria. The adverse event must be related to the treatment (paclitaxel or radiation) to be considered a DLT	Second Dose Cohort (20mg/m2 Taxol) MWF and Daily RT On Mondays, Wednesdays, and Fridays, paclitaxel infusion will given. On Monday, Tuesday, Wednesday, Thursday, Friday Thoracic XRT will be given. A minimum of three patients will be assigned at each dose level. If no DLTs are observed then the next three patients enrolled will receive a dose of 5 mg/m2 per dose more than the previous group. If one or two instances of DLT are observed then an additional three patients will be tested at the same dose. If DLT is observed in at most two of six patients then dose escalation will continue in the next three patients enrolled. Dose-limiting toxicity (DLT) is defined as grade 4 hematologic toxicity, or grade 3 and 4 non-hematologic toxicity excluding nausea and vomiting according to RTOG and Cooperative Group common toxicity criteria. The adverse event must be related to the treatment (paclitaxel or radiation) to be considered a DLT	Third Dose Cohort (25mg/m2 Taxol) MWF and Daily RT A minimum of three patients will be assigned at each dose level. If no DLTs are observed then the next three patients enrolled will receive a dose of 5 mg/m2 per dose more than the previous group. If one or two instances of DLT are observed then an additional three patients will be tested at the same dose. If DLT is observed in at most two of six patients then dose escalation will continue in the next three patients enrolled. Dose-limiting toxicity (DLT) is defined as grade 4 hematologic toxicity, or grade 3 and 4 non-hematologic toxicity excluding nausea and vomiting according to RTOG and Cooperative Group common toxicity criteria. The adverse event must be related to the treatment (paclitaxel or radiation) to be considered a DLT	Phase II Group (20mg/m2 Taxol) Once the MTD has been determined and confirmed with a total of six patients, up to 19 additional patients with measurable disease will be enrolled at that dose in order to obtain estimates of response rate and more information about toxicity Phase II enrollment will be in two stages. Initially 9 or 12 patients (depending on how many were tested at the MTD dose in the Phase I study) will be tested, for a total of 15 patients at the MTD. If fewer than 4 responses are observed, the study will end with 90% confidence that the true response rate is no greater than 40%, which is the minimum clinically interesting response rate. If four or more responses are observed, additional patients will be enrolled to obtain 25 evaluable patients at the MTD. This will allow estimation of the true response rate and toxicity rates with standard errors of no more than 0.1.
Overall Study STARTED	10	7	6	18
Overall Study COMPLETED	6	6	6	16
Overall Study NOT COMPLETED	4	1	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	First Dose Cohort (15mg/m2 Taxol) MWF and Daily RT On Mondays, Wednesdays, and Fridays, paclitaxel infusion will given. On Monday, Tuesday, Wednesday, Thursday, Friday Thoracic XRT will be given. A minimum of three patients will be assigned at each dose level. If no DLTs are observed then the next three patients enrolled will receive a dose of 5 mg/m2 per dose more than the previous group. If one or two instances of DLT are observed then an additional three patients will be tested at the same dose. If DLT is observed in at most two of six patients then dose escalation will continue in the next three patients enrolled. Dose-limiting toxicity (DLT) is defined as grade 4 hematologic toxicity, or grade 3 and 4 non-hematologic toxicity excluding nausea and vomiting according to RTOG and Cooperative Group common toxicity criteria. The adverse event must be related to the treatment (paclitaxel or radiation) to be considered a DLT	Second Dose Cohort (20mg/m2 Taxol) MWF and Daily RT On Mondays, Wednesdays, and Fridays, paclitaxel infusion will given. On Monday, Tuesday, Wednesday, Thursday, Friday Thoracic XRT will be given. A minimum of three patients will be assigned at each dose level. If no DLTs are observed then the next three patients enrolled will receive a dose of 5 mg/m2 per dose more than the previous group. If one or two instances of DLT are observed then an additional three patients will be tested at the same dose. If DLT is observed in at most two of six patients then dose escalation will continue in the next three patients enrolled. Dose-limiting toxicity (DLT) is defined as grade 4 hematologic toxicity, or grade 3 and 4 non-hematologic toxicity excluding nausea and vomiting according to RTOG and Cooperative Group common toxicity criteria. The adverse event must be related to the treatment (paclitaxel or radiation) to be considered a DLT	Phase II Group (20mg/m2 Taxol) Once the MTD has been determined and confirmed with a total of six patients, up to 19 additional patients with measurable disease will be enrolled at that dose in order to obtain estimates of response rate and more information about toxicity Phase II enrollment will be in two stages. Initially 9 or 12 patients (depending on how many were tested at the MTD dose in the Phase I study) will be tested, for a total of 15 patients at the MTD. If fewer than 4 responses are observed, the study will end with 90% confidence that the true response rate is no greater than 40%, which is the minimum clinically interesting response rate. If four or more responses are observed, additional patients will be enrolled to obtain 25 evaluable patients at the MTD. This will allow estimation of the true response rate and toxicity rates with standard errors of no more than 0.1.
Overall Study Adverse Event	2	0	0
Overall Study Death	0	1	1
Overall Study Cancer progression	2	0	1

Baseline Characteristics

Pulsed Paclitaxel And Daily Thoracic Radiotherapy For Inoperable (Stage I/II) Or Unresectable Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Daily RT Plus Chemo on MWF n=41 Participants Paclitaxel On Mondays, Wednesdays, and Fridays, paclitaxel infusion will begin early in the morning and complete before 10:30 am. On Monday, Tuesday, Wednesday, Thursday, Friday Thoracic XRT will be given in late afternoon, after 4:00 PM, if possible Radiation Therapy : Thoracic XRT will be given in late afternoon, after 4:00 PM, if possible Paclitaxel : On Mondays, Wednesdays, and Fridays, paclitaxel infusion will begin early in the morning and complete before 10:30 am.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	18 Participants n=5 Participants
Age, Categorical >=65 years	23 Participants n=5 Participants
Age, Continuous	63.3 years STANDARD_DEVIATION 11.3 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants
Region of Enrollment United States	41 participants n=5 Participants

PRIMARY outcome

Timeframe: 5 years

Outcome measures

Outcome measures
Measure	1st Dose Cohort 15mg/m2 Taxol Plus RT n=10 Participants 15 mg/m2 Paclitaxel On Mondays, Wednesdays, and Fridays, paclitaxel infusion will begin early in the morning and complete before 10:30 am. On Monday, Tuesday, Wednesday, Thursday, Friday Thoracic XRT will be given in late afternoon, after 4:00 PM, if possible Paclitaxel: On Mondays, Wednesdays, and Fridays, paclitaxel infusion will begin early in the morning and complete before 10:30 am. Radiation Therapy: Thoracic XRT will be given in late afternoon, after 4:00 PM, if possible	2nd Dose cohort20 mg/m2 Taxol Plus Daily RT n=7 Participants Paclitaxel: On Mondays, Wednesdays, and Fridays, paclitaxel infusion will begin early in the morning and complete before 10:30 am. Radiation Therapy: Thoracic XRT will be given in late afternoon, after 4:00 PM, if possible	3rd Dose Cohort --25mg/m2 Taxol Plus RT n=6 Participants Paclitaxel: On Mondays, Wednesdays, and Fridays, paclitaxel infusion will begin early in the morning and complete before 10:30 am. Radiation Therapy: Thoracic XRT will be given in late afternoon, after 4:00 PM, if possible
Define the Maximum Tolerated Dose (MTD) Using This Dose Schedule.	20 Percentage subj w dose limiting toxicity	28.6 Percentage subj w dose limiting toxicity	33.3 Percentage subj w dose limiting toxicity

SECONDARY outcome

Timeframe: 86 months

This is median survival for all subjects enrolled.

Outcome measures

Outcome measures
Measure	1st Dose Cohort 15mg/m2 Taxol Plus RT n=41 Participants 15 mg/m2 Paclitaxel On Mondays, Wednesdays, and Fridays, paclitaxel infusion will begin early in the morning and complete before 10:30 am. On Monday, Tuesday, Wednesday, Thursday, Friday Thoracic XRT will be given in late afternoon, after 4:00 PM, if possible Paclitaxel: On Mondays, Wednesdays, and Fridays, paclitaxel infusion will begin early in the morning and complete before 10:30 am. Radiation Therapy: Thoracic XRT will be given in late afternoon, after 4:00 PM, if possible	2nd Dose cohort20 mg/m2 Taxol Plus Daily RT Paclitaxel: On Mondays, Wednesdays, and Fridays, paclitaxel infusion will begin early in the morning and complete before 10:30 am. Radiation Therapy: Thoracic XRT will be given in late afternoon, after 4:00 PM, if possible	3rd Dose Cohort --25mg/m2 Taxol Plus RT Paclitaxel: On Mondays, Wednesdays, and Fridays, paclitaxel infusion will begin early in the morning and complete before 10:30 am. Radiation Therapy: Thoracic XRT will be given in late afternoon, after 4:00 PM, if possible
Median Survival	10.2 months Interval 1.4 to 85.6	—	—

Adverse Events

All Subjects Enrolled

Serious events: 7 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	All Subjects Enrolled n=18 participants at risk；n=41 participants at risk
Gastrointestinal disorders Esophagitis	2.4% 1/41 • Number of events 1
Respiratory, thoracic and mediastinal disorders Adult Respiratory distress syndrome	4.9% 2/41 • Number of events 2
Infections and infestations Infection	2.4% 1/41 • Number of events 1
Vascular disorders Thromboembolic event	2.4% 1/41 • Number of events 1
Respiratory, thoracic and mediastinal disorders bronchopulmonary hemorrhage	2.4% 1/41 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	2.4% 1/41 • Number of events 1

Other adverse events

Other adverse events
Measure	All Subjects Enrolled n=18 participants at risk；n=41 participants at risk
Respiratory, thoracic and mediastinal disorders pneumonitis	16.7% 3/18 • Number of events 3
Gastrointestinal disorders Esophagitis	16.7% 3/18 • Number of events 3

Additional Information

Yuhchyau Chen MD, PhD

University of Rochester

Phone: 585-275-5575

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place