STAGE IIIA/B NSCLC / INOPERABLE LUNG CANCER
Conditions
Keywords
STAGE IIIA/B NSCLC / INOPERABLE LUNG CANCER
Brief summary
The investigators propose this phase I/II study to use weekly Nab-Paclitaxel (Abraxane) and carboplatin with concurrent radiation in local-regionally advanced lung cancer. There are no published human studies combining Nab-Paclitaxel (Abraxane) with radiation. The investigators will first confirm the tolerated dose (TD) of concurrent Nab-Paclitaxel (Abraxane) at 50mg/m2, and then will begin enrolling patients into the phase II component using either Nab-Paclitaxel (Abraxane) at the TD with carboplatin concurrent with daily radiation or paclitaxel with carboplatin concurrent with daily radiation.
Interventions
DRUGNAB-PACLITAXEL
nab-Paclitaxel 50 mg/m2 IV/30min/wk x6 wks
DRUGPACLITAXEL
Sponsors
Celgene
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is Phase I/II study. Phase I has 1 arm and Phase II has 2 arms (total 3 arms)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically documented NSCLC; Patients must be M0. Patients with T1-T2 with N2 or T3N1-2 are eligible, if inoperable. Patients with T4 with any N or any T with N2 or N3 disease are eligible if unresectable. * Patients with tumors adjacent to a vertebral body are eligible as long as all gross disease can be encompassed in the radiation boost field. The boost volume must be limited to \< 50% of the ipsilateral lung volume. * Patients with Zubrod performance status 0-1 * Adequate hematologic function * FEV1 with ≥ 1200 cc or ≥ 50% predicted
Exclusion criteria
* Prior systemic chemotherapy (for lung cancer) and/or thoracic/neck radiotherapy for any reason and/or surgical resection of present cancer * Exudative, bloody, or cytologically malignant effusions * Prior therapy with any molecular targeted drugs (for lung cancer) * Active pulmonary infection not responsive to conventional antibiotics * Clinically significant cardiovascular event (e.g. myocardial infarction, superior vena cava syndrome (SVC), New York Heart Association (NYHA) classification of heart disease \>2 (see Appendix B) within 3 months before entry; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia. * Patients with \> grade 1 neuropathy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2-year Overall Survival (Phase II) | 2 years | 2-year overall survival, as measured (by Kaplan-Meir method) as the percentage of patients who were randomized and received carboplatin/paclitaxel or carboplatin/nab-paclitaxel with radiation therapy survived for 2 years. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate for the Patients Receiving Carboplatin/ Paclitaxel or Carboplatin/ Nab-paclitaxel With Radiation Therapy | 1,6,12,18,24 month | The objective response rate (ORR) is defined as the percentage of participants achieving complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST1.1) criteria |
| Proportion of Participants With Progression-free Survival (Phase II) | 2 years | Proportion of participants with progression free survival at 2 years is computed as the percentage of participants between randomization and local or regional progression, distant metastases, death, or last known follow-up. Estimates of progression free survival will be calculated using the Kaplan-Meir method. |
| Median Overall Survival (Phase II) | every 6 months up to 24 months (approx. 22 months) | Median overall survival was based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive. |
| EuroQol-5Dimension (EQ-5D) MUS Score at Baseline | Baseline | EQ-5D is a two-part questionnaire. The first part of mean utility score (MUS) consists of five items addressing five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension can be graded on three levels: 1-no problems, 2- slight problems, and 3-moderate problems, 4-severe problems, 5-extreme problems. Possible score ranges from 5-25 with higher scores indicating worse outcome.Both the five-item index score and the VAS score are transformed into a utility score between 0-worst health state and 1-best health state. |
| The Feasibility of Concurrent Carboplatin/Nab-Paclitaxel and Radiation Therapy | 60 days of the start of treatment | The feasibility as measured by the number of participants who had grade 3 or higher radiation related esophagitis or pulmonary toxicity or chemotherapy related grade 4 hematological or other non-hematological toxicities occurring within 60 days of the start of treatment; compliance us defined as the completion of the treatment regimen with no more than minor variations. |
| EuroQol-5Dimension (EQ-5D) VAS Score at Baseline | Baseline | The second part of the EQ-5D is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm 10-point-interval scale. Worst imaginable health state is scored as 0 at the bottom of the scale, and best imaginable health state is scored as 100 at the top. Possible score ranges from 0-100 with higher scores indicating better outcome. |
| EuroQol-5Dimension (EQ-5D) VAS Score at End of Treatment | End of Treatment (6 weeks) | The second part of the EQ-5D is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm 10-point-interval scale. Worst imaginable health state is scored as 0 at the bottom of the scale, and best imaginable health state is scored as 100 at the top. Possible score ranges from 0-100 with higher scores indicating better outcome. |
| EuroQol-5Dimension (EQ-5D) VAS Score at 24 Month Follow up | 24 month follow up | The second part of the EQ-5D is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm 10-point-interval scale. Worst imaginable health state is scored as 0 at the bottom of the scale, and best imaginable health state is scored as 100 at the top. Possible score ranges from 0-100 with higher scores indicating better outcome. |
| EuroQol-5Dimension (EQ-5D) MUS Score at 24 Month | 24 month follow up | EQ-5D is a two-part questionnaire. The first part of mean utility score (MUS) consists of five items addressing five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension can be graded on three levels: 1-no problems, 2- slight problems, and 3-moderate problems, 4-severe problems, 5-extreme problems. Possible score ranges from 5-25 with higher scores indicating worse outcome.Both the five-item index score and the VAS score are transformed into a utility score between 0-worst health state and 1-best health state. |
| EuroQol-5Dimension (EQ-5D) MUS Score at End of Treatment | End of treatment (6 weeks) | EQ-5D is a two-part questionnaire. The first part of mean utility score (MUS) consists of five items addressing five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension can be graded on three levels: 1-no problems, 2- slight problems, and 3-moderate problems, 4-severe problems, 5-extreme problems. Possible score ranges from 5-25 with higher scores indicating worse outcome. Both the five-item index score and the VAS score are transformed into a utility score between 0-worst health state and 1-best health state. |
Countries
United States
Participant flow
Pre-assignment details
6 patients enrolled in phase I and 92 patients enrolled in phase II, 46 patints were randomized to Arm A, and 46 patients to Arm B.
Participants by arm
| Arm | Count |
|---|---|
| NAB-PACLITAXEL (Phase I) NAB-PACLITAXEL PLUS CARBOPLATIN WITH CONCURRENT RADIATION THERAPY nab-Paclitaxel 50 mg/m2 IV/30min/wk x6 wks
NAB-PACLITAXEL: nab-Paclitaxel 50 mg/m2 IV/30min/wk x6 wks | 6 |
| PACLITAXEL (Phase II, Arm A) PACLITAXEL PLUS CARBOPLATIN WITH CONCURRENT RADIATION THERAPY Paclitaxel 50 mg/m2 IV/1h/wk\* x6 wks Carboplatin AUC \*\*2 IV/30 min/wk x6 wks XRT 6000 cGy | 46 |
| NAB-PACLITAXEL (Phase II, Arm B) NAB-PACLITAXEL PLUS CARBOPLATIN WITH CONCURRENT RADIATION THERAPY nab-Paclitaxel 40 mg/m2 IV/30min/wk x6 wks Carboplatin AUC \*\*2 IV/30 min/wk x6 wks XRT 6000 cGy | 46 |
| Total | 98 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | >2 weeks treatment break | 0 | 0 | 1 |
| Overall Study | Consent withdrawal | 0 | 4 | 4 |
| Overall Study | Liver metastasis identified at CT simulation | 0 | 1 | 0 |
| Overall Study | Mulitple hospitalization ( after first week of CRT) | 0 | 0 | 1 |
| Overall Study | Multiple missed appointments | 0 | 1 | 0 |
| Overall Study | Not meeting protocol constraints | 0 | 1 | 1 |
| Overall Study | Patient death prior to starting treatment | 0 | 0 | 1 |
| Overall Study | Patient off study, IRB hold. | 0 | 0 | 1 |
| Overall Study | Wrong medication administered | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | NAB-PACLITAXEL (Phase I) | PACLITAXEL (Phase II, Arm A) | NAB-PACLITAXEL (Phase II, Arm B) | Total |
|---|---|---|---|---|
| Age, Customized Median age, years | 64 months,years | 65.5 months,years | 66.5 months,years | 66 months,years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 45 Participants | 45 Participants | 96 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 6 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 6 Participants | 41 Participants | 38 Participants | 85 Participants |
| Sex: Female, Male Female | 2 Participants | 26 Participants | 20 Participants | 48 Participants |
| Sex: Female, Male Male | 4 Participants | 20 Participants | 26 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 2 / 38 | 3 / 37 |
| other Total, other adverse events | 0 / 6 | 38 / 38 | 37 / 37 |
| serious Total, serious adverse events | 0 / 6 | 0 / 38 | 0 / 37 |
Outcome results
Primary
2-year Overall Survival (Phase II)
2-year overall survival, as measured (by Kaplan-Meir method) as the percentage of patients who were randomized and received carboplatin/paclitaxel or carboplatin/nab-paclitaxel with radiation therapy survived for 2 years.
Time frame: 2 years
Population: This outcome was collected for Phase II participants only 2- year overall survival.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| PACLITAXEL (Phase II, Arm A) | 2-year Overall Survival (Phase II) | 66.5 percentage of participants |
| NAB-PACLITAXEL (Phase II, Arm B) | 2-year Overall Survival (Phase II) | 55.5 percentage of participants |
Secondary
EuroQol-5Dimension (EQ-5D) MUS Score at 24 Month
EQ-5D is a two-part questionnaire. The first part of mean utility score (MUS) consists of five items addressing five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension can be graded on three levels: 1-no problems, 2- slight problems, and 3-moderate problems, 4-severe problems, 5-extreme problems. Possible score ranges from 5-25 with higher scores indicating worse outcome.Both the five-item index score and the VAS score are transformed into a utility score between 0-worst health state and 1-best health state.
Time frame: 24 month follow up
Population: This outcome measure was only collected for one participant a 24 months due t oall other participants not completing the QOL timepoint
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PACLITAXEL (Phase II, Arm A) | EuroQol-5Dimension (EQ-5D) MUS Score at 24 Month | 0.47 score on a scale |
Secondary
EuroQol-5Dimension (EQ-5D) MUS Score at Baseline
EQ-5D is a two-part questionnaire. The first part of mean utility score (MUS) consists of five items addressing five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension can be graded on three levels: 1-no problems, 2- slight problems, and 3-moderate problems, 4-severe problems, 5-extreme problems. Possible score ranges from 5-25 with higher scores indicating worse outcome.Both the five-item index score and the VAS score are transformed into a utility score between 0-worst health state and 1-best health state.
Time frame: Baseline
Population: This outcome was measure from Phase II participants only
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PACLITAXEL (Phase II, Arm A) | EuroQol-5Dimension (EQ-5D) MUS Score at Baseline | 0.49 score on a scale |
| NAB-PACLITAXEL (Phase II, Arm B) | EuroQol-5Dimension (EQ-5D) MUS Score at Baseline | 0.44 score on a scale |
Secondary
EuroQol-5Dimension (EQ-5D) MUS Score at End of Treatment
EQ-5D is a two-part questionnaire. The first part of mean utility score (MUS) consists of five items addressing five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension can be graded on three levels: 1-no problems, 2- slight problems, and 3-moderate problems, 4-severe problems, 5-extreme problems. Possible score ranges from 5-25 with higher scores indicating worse outcome. Both the five-item index score and the VAS score are transformed into a utility score between 0-worst health state and 1-best health state.
Time frame: End of treatment (6 weeks)
Population: This outcome was measure from Phase II participants only
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PACLITAXEL (Phase II, Arm A) | EuroQol-5Dimension (EQ-5D) MUS Score at End of Treatment | 0.55 score on a scale |
| NAB-PACLITAXEL (Phase II, Arm B) | EuroQol-5Dimension (EQ-5D) MUS Score at End of Treatment | 0.45 score on a scale |
Secondary
EuroQol-5Dimension (EQ-5D) VAS Score at 24 Month Follow up
The second part of the EQ-5D is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm 10-point-interval scale. Worst imaginable health state is scored as 0 at the bottom of the scale, and best imaginable health state is scored as 100 at the top. Possible score ranges from 0-100 with higher scores indicating better outcome.
Time frame: 24 month follow up
Population: This outcome measure was only collected for one participant a 24 months due to all other participants not completing the QOL timepoint
| Arm | Measure | Value (MEAN) |
|---|---|---|
| PACLITAXEL (Phase II, Arm A) | EuroQol-5Dimension (EQ-5D) VAS Score at 24 Month Follow up | 0.6 score on a scale |
Secondary
EuroQol-5Dimension (EQ-5D) VAS Score at Baseline
The second part of the EQ-5D is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm 10-point-interval scale. Worst imaginable health state is scored as 0 at the bottom of the scale, and best imaginable health state is scored as 100 at the top. Possible score ranges from 0-100 with higher scores indicating better outcome.
Time frame: Baseline
Population: This outcome was measure from Phase II participants only
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PACLITAXEL (Phase II, Arm A) | EuroQol-5Dimension (EQ-5D) VAS Score at Baseline | 0.80 score on a scale |
| NAB-PACLITAXEL (Phase II, Arm B) | EuroQol-5Dimension (EQ-5D) VAS Score at Baseline | 0.79 score on a scale |
Secondary
EuroQol-5Dimension (EQ-5D) VAS Score at End of Treatment
The second part of the EQ-5D is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm 10-point-interval scale. Worst imaginable health state is scored as 0 at the bottom of the scale, and best imaginable health state is scored as 100 at the top. Possible score ranges from 0-100 with higher scores indicating better outcome.
Time frame: End of Treatment (6 weeks)
Population: This outcome was measure from Phase II participants only
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PACLITAXEL (Phase II, Arm A) | EuroQol-5Dimension (EQ-5D) VAS Score at End of Treatment | 0.64 score on a scale |
| NAB-PACLITAXEL (Phase II, Arm B) | EuroQol-5Dimension (EQ-5D) VAS Score at End of Treatment | 0.78 score on a scale |
Secondary
Median Overall Survival (Phase II)
Median overall survival was based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.
Time frame: every 6 months up to 24 months (approx. 22 months)
Population: This outcome was measured from Phase II participants only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PACLITAXEL (Phase II, Arm A) | Median Overall Survival (Phase II) | NA months |
| NAB-PACLITAXEL (Phase II, Arm B) | Median Overall Survival (Phase II) | 27.8 months |
Secondary
Overall Response Rate for the Patients Receiving Carboplatin/ Paclitaxel or Carboplatin/ Nab-paclitaxel With Radiation Therapy
The objective response rate (ORR) is defined as the percentage of participants achieving complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST1.1) criteria
Time frame: 1,6,12,18,24 month
Population: This outcome was measured from Phase II participants only. Percent CR/PR rates by treatment arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PACLITAXEL (Phase II, Arm A) | Overall Response Rate for the Patients Receiving Carboplatin/ Paclitaxel or Carboplatin/ Nab-paclitaxel With Radiation Therapy | 6 month scan | 21.1 percentage of participants |
| PACLITAXEL (Phase II, Arm A) | Overall Response Rate for the Patients Receiving Carboplatin/ Paclitaxel or Carboplatin/ Nab-paclitaxel With Radiation Therapy | 18 month scan | 10.5 percentage of participants |
| PACLITAXEL (Phase II, Arm A) | Overall Response Rate for the Patients Receiving Carboplatin/ Paclitaxel or Carboplatin/ Nab-paclitaxel With Radiation Therapy | 12 month scan | 10.5 percentage of participants |
| PACLITAXEL (Phase II, Arm A) | Overall Response Rate for the Patients Receiving Carboplatin/ Paclitaxel or Carboplatin/ Nab-paclitaxel With Radiation Therapy | 24 month scan | 2.6 percentage of participants |
| PACLITAXEL (Phase II, Arm A) | Overall Response Rate for the Patients Receiving Carboplatin/ Paclitaxel or Carboplatin/ Nab-paclitaxel With Radiation Therapy | 1 month scan | 36.8 percentage of participants |
| NAB-PACLITAXEL (Phase II, Arm B) | Overall Response Rate for the Patients Receiving Carboplatin/ Paclitaxel or Carboplatin/ Nab-paclitaxel With Radiation Therapy | 24 month scan | 8.1 percentage of participants |
| NAB-PACLITAXEL (Phase II, Arm B) | Overall Response Rate for the Patients Receiving Carboplatin/ Paclitaxel or Carboplatin/ Nab-paclitaxel With Radiation Therapy | 1 month scan | 45.9 percentage of participants |
| NAB-PACLITAXEL (Phase II, Arm B) | Overall Response Rate for the Patients Receiving Carboplatin/ Paclitaxel or Carboplatin/ Nab-paclitaxel With Radiation Therapy | 6 month scan | 24.3 percentage of participants |
| NAB-PACLITAXEL (Phase II, Arm B) | Overall Response Rate for the Patients Receiving Carboplatin/ Paclitaxel or Carboplatin/ Nab-paclitaxel With Radiation Therapy | 12 month scan | 13.5 percentage of participants |
| NAB-PACLITAXEL (Phase II, Arm B) | Overall Response Rate for the Patients Receiving Carboplatin/ Paclitaxel or Carboplatin/ Nab-paclitaxel With Radiation Therapy | 18 month scan | 5.4 percentage of participants |
Secondary
Proportion of Participants With Progression-free Survival (Phase II)
Proportion of participants with progression free survival at 2 years is computed as the percentage of participants between randomization and local or regional progression, distant metastases, death, or last known follow-up. Estimates of progression free survival will be calculated using the Kaplan-Meir method.
Time frame: 2 years
Population: This outcome was collected from Phase II participants only
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PACLITAXEL (Phase II, Arm A) | Proportion of Participants With Progression-free Survival (Phase II) | 44.4 percentage of participants |
| NAB-PACLITAXEL (Phase II, Arm B) | Proportion of Participants With Progression-free Survival (Phase II) | 27.3 percentage of participants |
Secondary
The Feasibility of Concurrent Carboplatin/Nab-Paclitaxel and Radiation Therapy
The feasibility as measured by the number of participants who had grade 3 or higher radiation related esophagitis or pulmonary toxicity or chemotherapy related grade 4 hematological or other non-hematological toxicities occurring within 60 days of the start of treatment; compliance us defined as the completion of the treatment regimen with no more than minor variations.
Time frame: 60 days of the start of treatment
Population: This outcome was collected for Phase I participants only. (6 total).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NAB-PACLITAXEL (Phase I) | The Feasibility of Concurrent Carboplatin/Nab-Paclitaxel and Radiation Therapy | 0 Participants |