Trial Outcomes & Findings for Bortezomib, Paclitaxel, Carboplatin and Radiation Therapy for Non-Small Cell Lung Cancer (NCT NCT00093756)
NCT ID: NCT00093756
Last Updated: 2017-12-07
Results Overview
The primary endpoint of this trial is the proportion of patients alive at 1 year (i.e., 365 days) after study registration. Proportion of successes, defined as the number of patients alive at one year divided by the total number of evaluable patients.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
52 participants
Primary outcome timeframe
At 1 year
Results posted on
2017-12-07
Participant Flow
Fifty two (52) patients were accrued, out of which 4 were cancels. Twenty one (21) patients were accrued for phase I portion of the study. Twenty Seven (27) patients are accrued for phase II portion of the study. Twenty Seven (27) Phase II patients are evaluable for primary outcome measure.
Participant milestones
| Measure |
Phase I
PHASE I: Cohorts of 3-6 patients receive escalating doses of study medications until the maximum tolerated dose (MTD) is determined. 3-dimensional conformal radiation therapy, bortezomib: Given IV, paclitaxel: Given IV, carboplatin: Given IV.
|
Phase II
PHASE II: Patients receive as in phase I at the MTD. Patients also undergo radiotherapy as in phase I. 3-dimensional conformal radiation therapy, bortezomib: Given IV, paclitaxel: Given IV, , carboplatin: Given IV.
|
|---|---|---|
|
Overall Study
STARTED
|
27
|
21
|
|
Overall Study
COMPLETED
|
27
|
21
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Bortezomib, Paclitaxel, Carboplatin and Radiation Therapy for Non-Small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
PhaseI
n=27 Participants
PHASE I: Cohorts of 3-6 patients receive escalating doses of study medications until the maximum tolerated dose (MTD) is determined. 3-dimensional conformal radiation therapy\> bortezomib: Given IV\> paclitaxel: Given IV\> carboplatin: Given IV
|
PhaseII
n=21 Participants
PHASE II: Patients receive as in phase I at the MTD. Patients also undergo radiotherapy as in phase I. 3-dimensional conformal radiation therapy\> bortezomib: Given IV\> paclitaxel: Given IV\> carboplatin: Given IV
|
Total
n=48 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63 years
n=5 Participants
|
58 years
n=7 Participants
|
58 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
21 participants
n=5 Participants
|
27 participants
n=7 Participants
|
48 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: At 1 yearPopulation: This analysis included all 21 patients enrolled in the Phase II portion of the study and 6 patients enrolled in the Phase I who were treated at the Phase II dose level.
The primary endpoint of this trial is the proportion of patients alive at 1 year (i.e., 365 days) after study registration. Proportion of successes, defined as the number of patients alive at one year divided by the total number of evaluable patients.
Outcome measures
| Measure |
PhaseII
n=27 Participants
PHASE II: Patients receive as in phase I at the MTD. Patients also undergo radiotherapy as in phase I. 3-dimensional conformal radiation therapy, bortezomib: Given IV, paclitaxel: Given IV, carboplatin: Given IV.
|
|---|---|
|
The Primary Endpoint of This Trial is the Proportion of Patients Alive at 1 Year. Phase II Patients Only.
|
0.73 proportion of Participants
|
SECONDARY outcome
Timeframe: Up to 5 yearsPopulation: All 21 patients from Phase II and 6 patients registered to the Phase II dose level of Phase I were included in this analysis.
Response was assessed using the RECIST v1.1 criteria. Patients were evaluated at 4 weeks post-RT, 3 months post-RT, every 3 months for 1 year post-RT, and every 6 months thereafter for a maximum of 5 years from time of registration. A Complete Response (CR) is defined as the disappearance of all target lesions. A Partial Response (PR) is defined as at least a 20% decrease in the sum of the longest diameter of target lesions from baseline. A confirmed response is defined as a CR or PR as the objective status on 2 consecutive evaluations at least 4 weeks apart.
Outcome measures
| Measure |
PhaseII
n=27 Participants
PHASE II: Patients receive as in phase I at the MTD. Patients also undergo radiotherapy as in phase I. 3-dimensional conformal radiation therapy, bortezomib: Given IV, paclitaxel: Given IV, carboplatin: Given IV.
|
|---|---|
|
Confirmed Tumor Response
Complete Response (CR)
|
3 Participants
|
|
Confirmed Tumor Response
Partial Response (PR)
|
4 Participants
|
SECONDARY outcome
Timeframe: From study registration to date of disease progression or date of last follow-up, up to 5 yearsPopulation: Study team decision not to run this analysis.
The distribution of time to progression will be estimated using the method of Kaplan-Meier.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From study registration to the first of either death due to any cause or progression, up to 5 yearsPopulation: All 21 patients from Phase II and 6 patients registered to the Phase II dose level of Phase I were included in this analysis.
The distribution of progression-free survival (PFS) is defined as the time from registration to the time of progression or death, whichever comes first. The PFS will be estimated using the method of Kaplan-Meier.
Outcome measures
| Measure |
PhaseII
n=27 Participants
PHASE II: Patients receive as in phase I at the MTD. Patients also undergo radiotherapy as in phase I. 3-dimensional conformal radiation therapy, bortezomib: Given IV, paclitaxel: Given IV, carboplatin: Given IV.
|
|---|---|
|
Progression-free Survival
|
8.4 months
Interval 4.1 to 10.5
|
SECONDARY outcome
Timeframe: From registration to death due to any cause, up to 5 yearsPopulation: All 21 patients from Phase II and 6 patients registered to the Phase II dose level of Phase I were included in this analysis.
Overall Survival is defined as the time from registration to the time to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.
Outcome measures
| Measure |
PhaseII
n=27 Participants
PHASE II: Patients receive as in phase I at the MTD. Patients also undergo radiotherapy as in phase I. 3-dimensional conformal radiation therapy, bortezomib: Given IV, paclitaxel: Given IV, carboplatin: Given IV.
|
|---|---|
|
Overall Survival
|
25 months
Interval 15.6 to 35.8
|
SECONDARY outcome
Timeframe: Up to 5 yearsPopulation: All 21 patients from Phase II and 6 patients registered to the Phase II dose level of Phase I were included in this analysis.
Toxicity was reported after the first 21 days of treatment and after each 28 day cycle thereafter. Events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. The number of patients reporting grade 3 and higher are tabulated.
Outcome measures
| Measure |
PhaseII
n=27 Participants
PHASE II: Patients receive as in phase I at the MTD. Patients also undergo radiotherapy as in phase I. 3-dimensional conformal radiation therapy, bortezomib: Given IV, paclitaxel: Given IV, carboplatin: Given IV.
|
|---|---|
|
Frequency and Severity of Observed Toxicity, Graded by Common Terminology Criteria for Adverse Events (CTCAE)
Grade 3 Adverse Event
|
22 Participants
|
|
Frequency and Severity of Observed Toxicity, Graded by Common Terminology Criteria for Adverse Events (CTCAE)
Grade 4 Adverse Event
|
15 Participants
|
Adverse Events
PhaseI
Serious events: 9 serious events
Other events: 21 other events
Deaths: 0 deaths
PhaseII
Serious events: 12 serious events
Other events: 27 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
PhaseI
n=21 participants at risk
PHASE I: Cohorts of 3-6 patients receive escalating doses of study medications until the maximum tolerated dose (MTD) is determined. 3-dimensional conformal radiation therapy, bortezomib: Given IV, paclitaxel: Given IV, carboplatin: Given IV.
|
PhaseII
n=27 participants at risk
PHASE II: Patients receive as in phase I at the MTD. Patients also undergo radiotherapy as in phase I. 3-dimensional conformal radiation therapy, bortezomib: Given IV, paclitaxel: Given IV, carboplatin: Given IV.
|
|---|---|---|
|
Cardiac disorders
Arrhythmia supraventricular
|
4.8%
1/21 • Number of events 1
|
0.00%
0/27
|
|
Cardiac disorders
Left ventricular failure
|
4.8%
1/21 • Number of events 1
|
0.00%
0/27
|
|
Cardiac disorders
Myocardial ischemia
|
9.5%
2/21 • Number of events 2
|
0.00%
0/27
|
|
Gastrointestinal disorders
Nausea
|
4.8%
1/21 • Number of events 1
|
7.4%
2/27 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
4.8%
1/21 • Number of events 1
|
0.00%
0/27
|
|
General disorders
Chest pain
|
4.8%
1/21 • Number of events 1
|
0.00%
0/27
|
|
General disorders
Fatigue
|
4.8%
1/21 • Number of events 1
|
7.4%
2/27 • Number of events 2
|
|
Infections and infestations
Pneumonia
|
4.8%
1/21 • Number of events 1
|
0.00%
0/27
|
|
Investigations
Cardiac troponin I increased
|
4.8%
1/21 • Number of events 1
|
0.00%
0/27
|
|
Investigations
Leukocyte count decreased
|
4.8%
1/21 • Number of events 1
|
18.5%
5/27 • Number of events 5
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/21
|
3.7%
1/27 • Number of events 2
|
|
Investigations
Neutrophil count decreased
|
4.8%
1/21 • Number of events 1
|
22.2%
6/27 • Number of events 6
|
|
Investigations
Platelet count decreased
|
0.00%
0/21
|
33.3%
9/27 • Number of events 9
|
|
Metabolism and nutrition disorders
Anorexia
|
4.8%
1/21 • Number of events 1
|
3.7%
1/27 • Number of events 1
|
|
Metabolism and nutrition disorders
Dehydration
|
14.3%
3/21 • Number of events 3
|
0.00%
0/27
|
|
Metabolism and nutrition disorders
Serum albumin decreased
|
0.00%
0/21
|
3.7%
1/27 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum calcium decreased
|
0.00%
0/21
|
3.7%
1/27 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum phosphate decreased
|
0.00%
0/21
|
3.7%
1/27 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum potassium decreased
|
0.00%
0/21
|
3.7%
1/27 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum sodium decreased
|
0.00%
0/21
|
3.7%
1/27 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/21
|
3.7%
1/27 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/21
|
3.7%
1/27 • Number of events 1
|
|
Nervous system disorders
Ataxia
|
0.00%
0/21
|
3.7%
1/27 • Number of events 1
|
|
Nervous system disorders
Depressed level of consciousness
|
0.00%
0/21
|
7.4%
2/27 • Number of events 2
|
|
Nervous system disorders
Dizziness
|
4.8%
1/21 • Number of events 1
|
0.00%
0/27
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/21
|
3.7%
1/27 • Number of events 1
|
|
Nervous system disorders
Syncope
|
4.8%
1/21 • Number of events 1
|
3.7%
1/27 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
9.5%
2/21 • Number of events 2
|
7.4%
2/27 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
4.8%
1/21 • Number of events 1
|
3.7%
1/27 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/21
|
7.4%
2/27 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/21
|
3.7%
1/27 • Number of events 1
|
|
Vascular disorders
Hypotension
|
4.8%
1/21 • Number of events 1
|
3.7%
1/27 • Number of events 1
|
|
Vascular disorders
Thrombosis
|
9.5%
2/21 • Number of events 2
|
0.00%
0/27
|
Other adverse events
| Measure |
PhaseI
n=21 participants at risk
PHASE I: Cohorts of 3-6 patients receive escalating doses of study medications until the maximum tolerated dose (MTD) is determined. 3-dimensional conformal radiation therapy, bortezomib: Given IV, paclitaxel: Given IV, carboplatin: Given IV.
|
PhaseII
n=27 participants at risk
PHASE II: Patients receive as in phase I at the MTD. Patients also undergo radiotherapy as in phase I. 3-dimensional conformal radiation therapy, bortezomib: Given IV, paclitaxel: Given IV, carboplatin: Given IV.
|
|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
9.5%
2/21 • Number of events 2
|
3.7%
1/27 • Number of events 1
|
|
Blood and lymphatic system disorders
Hemoglobin decreased
|
81.0%
17/21 • Number of events 36
|
85.2%
23/27 • Number of events 64
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/21
|
3.7%
1/27 • Number of events 2
|
|
Gastrointestinal disorders
Constipation
|
19.0%
4/21 • Number of events 5
|
14.8%
4/27 • Number of events 5
|
|
Gastrointestinal disorders
Diarrhea
|
52.4%
11/21 • Number of events 15
|
33.3%
9/27 • Number of events 16
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/21
|
7.4%
2/27 • Number of events 2
|
|
Gastrointestinal disorders
Dysphagia
|
81.0%
17/21 • Number of events 42
|
77.8%
21/27 • Number of events 40
|
|
Gastrointestinal disorders
Ear, nose and throat examination abnormal
|
28.6%
6/21 • Number of events 9
|
25.9%
7/27 • Number of events 8
|
|
Gastrointestinal disorders
Esophageal mucositis
|
28.6%
6/21 • Number of events 8
|
48.1%
13/27 • Number of events 17
|
|
Gastrointestinal disorders
Esophageal pain
|
0.00%
0/21
|
3.7%
1/27 • Number of events 1
|
|
Gastrointestinal disorders
Esophagitis
|
0.00%
0/21
|
3.7%
1/27 • Number of events 2
|
|
Gastrointestinal disorders
Mucositis oral
|
23.8%
5/21 • Number of events 8
|
33.3%
9/27 • Number of events 13
|
|
Gastrointestinal disorders
Nausea
|
71.4%
15/21 • Number of events 24
|
77.8%
21/27 • Number of events 35
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
7/21 • Number of events 10
|
44.4%
12/27 • Number of events 18
|
|
General disorders
Chest pain
|
4.8%
1/21 • Number of events 1
|
3.7%
1/27 • Number of events 1
|
|
General disorders
Fatigue
|
95.2%
20/21 • Number of events 60
|
96.3%
26/27 • Number of events 68
|
|
General disorders
Fever
|
19.0%
4/21 • Number of events 4
|
14.8%
4/27 • Number of events 5
|
|
General disorders
Pain
|
4.8%
1/21 • Number of events 2
|
0.00%
0/27
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/21
|
7.4%
2/27 • Number of events 2
|
|
Infections and infestations
Gingival infection
|
4.8%
1/21 • Number of events 1
|
3.7%
1/27 • Number of events 1
|
|
Infections and infestations
Paranasal sinus infection
|
0.00%
0/21
|
3.7%
1/27 • Number of events 1
|
|
Infections and infestations
Upper respiratory infection
|
4.8%
1/21 • Number of events 1
|
0.00%
0/27
|
|
Injury, poisoning and procedural complications
Radiation recall reaction (dermatologic)
|
47.6%
10/21 • Number of events 14
|
51.9%
14/27 • Number of events 21
|
|
Investigations
Alkaline phosphatase increased
|
4.8%
1/21 • Number of events 1
|
0.00%
0/27
|
|
Investigations
Creatinine increased
|
0.00%
0/21
|
3.7%
1/27 • Number of events 1
|
|
Investigations
INR increased
|
4.8%
1/21 • Number of events 2
|
0.00%
0/27
|
|
Investigations
Leukocyte count decreased
|
90.5%
19/21 • Number of events 36
|
81.5%
22/27 • Number of events 43
|
|
Investigations
Lymphocyte count decreased
|
14.3%
3/21 • Number of events 4
|
3.7%
1/27 • Number of events 1
|
|
Investigations
Neutrophil count decreased
|
81.0%
17/21 • Number of events 24
|
74.1%
20/27 • Number of events 34
|
|
Investigations
Platelet count decreased
|
61.9%
13/21 • Number of events 19
|
85.2%
23/27 • Number of events 31
|
|
Investigations
Weight loss
|
4.8%
1/21 • Number of events 1
|
3.7%
1/27 • Number of events 1
|
|
Metabolism and nutrition disorders
Anorexia
|
23.8%
5/21 • Number of events 5
|
14.8%
4/27 • Number of events 4
|
|
Metabolism and nutrition disorders
Blood glucose increased
|
9.5%
2/21 • Number of events 2
|
0.00%
0/27
|
|
Metabolism and nutrition disorders
Dehydration
|
19.0%
4/21 • Number of events 4
|
11.1%
3/27 • Number of events 3
|
|
Metabolism and nutrition disorders
Serum albumin decreased
|
4.8%
1/21 • Number of events 2
|
3.7%
1/27 • Number of events 2
|
|
Metabolism and nutrition disorders
Serum calcium decreased
|
4.8%
1/21 • Number of events 1
|
3.7%
1/27 • Number of events 2
|
|
Metabolism and nutrition disorders
Serum magnesium decreased
|
0.00%
0/21
|
3.7%
1/27 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum sodium decreased
|
4.8%
1/21 • Number of events 1
|
3.7%
1/27 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/21
|
3.7%
1/27 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/21
|
3.7%
1/27 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
0.00%
0/21
|
3.7%
1/27 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness
|
4.8%
1/21 • Number of events 1
|
3.7%
1/27 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
33.3%
7/21 • Number of events 10
|
44.4%
12/27 • Number of events 27
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
4.8%
1/21 • Number of events 1
|
3.7%
1/27 • Number of events 2
|
|
Nervous system disorders
Ataxia
|
0.00%
0/21
|
3.7%
1/27 • Number of events 1
|
|
Nervous system disorders
Depressed level of consciousness
|
4.8%
1/21 • Number of events 1
|
0.00%
0/27
|
|
Nervous system disorders
Dizziness
|
4.8%
1/21 • Number of events 1
|
3.7%
1/27 • Number of events 1
|
|
Nervous system disorders
Dysgeusia
|
4.8%
1/21 • Number of events 1
|
3.7%
1/27 • Number of events 1
|
|
Nervous system disorders
Extrapyramidal disorder
|
4.8%
1/21 • Number of events 1
|
0.00%
0/27
|
|
Nervous system disorders
Headache
|
4.8%
1/21 • Number of events 1
|
3.7%
1/27 • Number of events 2
|
|
Nervous system disorders
Neuralgia
|
4.8%
1/21 • Number of events 1
|
0.00%
0/27
|
|
Nervous system disorders
Peripheral motor neuropathy
|
4.8%
1/21 • Number of events 1
|
3.7%
1/27 • Number of events 3
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
52.4%
11/21 • Number of events 27
|
55.6%
15/27 • Number of events 38
|
|
Nervous system disorders
Syncope
|
0.00%
0/21
|
3.7%
1/27 • Number of events 1
|
|
Psychiatric disorders
Anxiety
|
4.8%
1/21 • Number of events 1
|
0.00%
0/27
|
|
Psychiatric disorders
Confusion
|
4.8%
1/21 • Number of events 1
|
0.00%
0/27
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/21
|
7.4%
2/27 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
0.00%
0/21
|
3.7%
1/27 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
9.5%
2/21 • Number of events 3
|
3.7%
1/27 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
66.7%
14/21 • Number of events 51
|
77.8%
21/27 • Number of events 45
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.00%
0/21
|
3.7%
1/27 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal stenosis
|
0.00%
0/21
|
3.7%
1/27 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal examination abnormal
|
19.0%
4/21 • Number of events 5
|
14.8%
4/27 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
23.8%
5/21 • Number of events 6
|
7.4%
2/27 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
4.8%
1/21 • Number of events 1
|
0.00%
0/27
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory disorder
|
4.8%
1/21 • Number of events 1
|
0.00%
0/27
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
19.0%
4/21 • Number of events 5
|
33.3%
9/27 • Number of events 13
|
|
Skin and subcutaneous tissue disorders
Rash desquamating
|
4.8%
1/21 • Number of events 1
|
3.7%
1/27 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Skin disorder
|
0.00%
0/21
|
3.7%
1/27 • Number of events 1
|
|
Vascular disorders
Hypotension
|
14.3%
3/21 • Number of events 4
|
3.7%
1/27 • Number of events 1
|
Additional Information
Alex A. Adjei, M.D., Ph.D.
Roswell Park Cancer Institute
Phone: 507/284- 9265
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60