Trial Outcomes & Findings for Bendamustine With Irinotecan Followed by Etoposide/Carboplatin for Patients With Extensive Stage Small Cell Lung Cancer (NCT NCT00856830)
NCT ID: NCT00856830
Last Updated: 2017-07-17
Results Overview
The determination of the dose limiting toxicity as defined by The National Cancer Institute Common Toxicity Criteria version 3 as follows: grade 4 neutropenia \>5 days; grade 3/4 febrile neutropenia; grade 4 thrombocytopenia; or grade \>2 non-hematologic toxicities (except for nausea/vomiting, alopecia, or fatigue).
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
30 participants
Primary outcome timeframe
9 weeks
Results posted on
2017-07-17
Participant Flow
Protocol Open to Accrual: April 2009, Primary Completion Date: May 2015 and Study Completion Date: May 2016. Recruitment location: University of Alabama at Birmingham and Georgia Cancer Specialists.
We are proposing a novel combination of bendamustine plus irinotecan followed by the standard regimen of etoposide with carboplatin. This will allow the investigation of response to the novel combination as well as any improvement in outcomes compared to historical controls.
Participant milestones
| Measure |
Phase I - Regimen A: Cohort I (80 mg/m2) - Bendamustine (B)
Participants were treated with irinotecan at 150 mg/m2 on day 1 followed by bendamustine (80 mg/m2) on days 1 and 2: every 21 days for a total of 3 cycles Participants with either objective response or stable disease after 3 cycles of Regimen A, received Regimen B as a consolidation. Carboplatin AUC6 (Day 1), Etoposide 100mg/m2 (Day 1,2,3) every 21 days for 3 cycles.
|
Phase I - Regimen A: Cohort II 100mg/m2) - (B)
Participants were treated with irinotecan at 150 mg/m2 on day 1 followed by bendamustine (100 mg/m2) on days 1 and 2: every 21 days for a total of 3 cycles.
Participants with either objective response or stable disease after 3 cycles of Regimen A, received Regimen B as a consolidation. Carboplatin AUC6 (Day 1), Etoposide 100mg/m2 (Day 1,2,3) every 21 days for 3 cycles.
|
Phase I - Regimen A: Cohort III (120 mg/M2) - (B)
Participants were treated with irinotecan at 150 mg/m2 on day 1 followed by bendamustine (120 mg/m2) on days 1 and 2: every 21 days for a total of 3 cycles.
Participants with either objective response or stable disease after 3 cycles of Regimen A, received Regimen B as a consolidation. Carboplatin AUC6 (Day 1), Etoposide 100mg/m2 (Day 1,2,3) every 21 days for 3 cycles.
|
Phase II - Regimen A: Cohort IV (B) 100 -120 mg/m2 (Day 1,2)
Participants were treated with irinotecan at 150 mg/m2 on day 1 followed by bendmustine on days 1 and 2 at bendamustine 100-120 mg/m2 (Day 1,2). This was repeated every 21 days for a total of 3 cycles.
Participants with either objective response or stable disease after 3 cycles of Regimen A, received Regimen B as a consolidation. Carboplatin AUC6 (Day 1), Etoposide 100mg/m2 (Day 1,2,3) every 21 days for 3 cycles.
|
|---|---|---|---|---|
|
Irinotecan & Bendamustine
STARTED
|
3
|
6
|
6
|
15
|
|
Irinotecan & Bendamustine
Maximum Tolerated Dose
|
3
|
6
|
6
|
12
|
|
Irinotecan & Bendamustine
COMPLETED
|
3
|
6
|
6
|
12
|
|
Irinotecan & Bendamustine
NOT COMPLETED
|
0
|
0
|
0
|
3
|
|
Regimen - B (Carboplatin & Etoposide)
STARTED
|
3
|
6
|
6
|
12
|
|
Regimen - B (Carboplatin & Etoposide)
COMPLETED
|
3
|
6
|
6
|
12
|
|
Regimen - B (Carboplatin & Etoposide)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Phase I - Regimen A: Cohort I (80 mg/m2) - Bendamustine (B)
Participants were treated with irinotecan at 150 mg/m2 on day 1 followed by bendamustine (80 mg/m2) on days 1 and 2: every 21 days for a total of 3 cycles Participants with either objective response or stable disease after 3 cycles of Regimen A, received Regimen B as a consolidation. Carboplatin AUC6 (Day 1), Etoposide 100mg/m2 (Day 1,2,3) every 21 days for 3 cycles.
|
Phase I - Regimen A: Cohort II 100mg/m2) - (B)
Participants were treated with irinotecan at 150 mg/m2 on day 1 followed by bendamustine (100 mg/m2) on days 1 and 2: every 21 days for a total of 3 cycles.
Participants with either objective response or stable disease after 3 cycles of Regimen A, received Regimen B as a consolidation. Carboplatin AUC6 (Day 1), Etoposide 100mg/m2 (Day 1,2,3) every 21 days for 3 cycles.
|
Phase I - Regimen A: Cohort III (120 mg/M2) - (B)
Participants were treated with irinotecan at 150 mg/m2 on day 1 followed by bendamustine (120 mg/m2) on days 1 and 2: every 21 days for a total of 3 cycles.
Participants with either objective response or stable disease after 3 cycles of Regimen A, received Regimen B as a consolidation. Carboplatin AUC6 (Day 1), Etoposide 100mg/m2 (Day 1,2,3) every 21 days for 3 cycles.
|
Phase II - Regimen A: Cohort IV (B) 100 -120 mg/m2 (Day 1,2)
Participants were treated with irinotecan at 150 mg/m2 on day 1 followed by bendmustine on days 1 and 2 at bendamustine 100-120 mg/m2 (Day 1,2). This was repeated every 21 days for a total of 3 cycles.
Participants with either objective response or stable disease after 3 cycles of Regimen A, received Regimen B as a consolidation. Carboplatin AUC6 (Day 1), Etoposide 100mg/m2 (Day 1,2,3) every 21 days for 3 cycles.
|
|---|---|---|---|---|
|
Irinotecan & Bendamustine
Death
|
0
|
0
|
0
|
2
|
|
Irinotecan & Bendamustine
Physician Decision
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Bendamustine With Irinotecan Followed by Etoposide/Carboplatin for Patients With Extensive Stage Small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Regimen A: Cohort I Bendamustine 80 mg/m2 (Day 1,2)
n=3 Participants
Participants were treated with irinotecan at 150 mg/m2 on day 1 followed by bendmustine on days 1 and 2 at increasing dose levels using a 3 + 3 design. The initial dose of bendamustine was 80 mg/m2 with incremental 20 mg/m2 dose escalation to a maximum of 120 mg/m2. This was repeated every 21 days for a total of 3 cycles.
|
Regimen A: Cohort II Bendamustine 100 mg/m2 (Day 1,2)
n=6 Participants
Participants were treated with irinotecan at 150 mg/m2 on day 1 followed by bendmustine on days 1 and 2 at increasing dose levels using a 3 + 3 design. The initial dose of bendamustine was 100 mg/m2 with incremental 20 mg/m2 dose escalation to a maximum of 120 mg/m2. This was repeated every 21 days for a total of 3 cycles.
|
Regimen A: Cohort III Bendamustine 120 mg/m2 (Day 1,2)
n=6 Participants
Participants were treated with irinotecan at 150 mg/m2 on day 1 followed by bendmustine on days 1 and 2 at increasing dose levels using a 3 + 3 design. The initial dose of bendamustine was 120 mg/m2 with incremental 20 mg/m2 dose escalation to a maximum of 120 mg/m2. This was repeated every 21 days for a total of 3 cycles.
|
Regimen A: Cohort IV Bendamustine 100 -120 mg/m2 (Day 1,2)
n=15 Participants
Participants were treated with irinotecan at 150 mg/m2 on day 1 followed by bendmustine on days 1 and 2 at increasing dose levels using a 3 + 3 design. Bendamustine was given at 100 - 120 mg/m2. This was repeated every 21 days for a total of 3 cycles.
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=157 Participants
|
0 Participants
n=390 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
13 Participants
n=157 Participants
|
27 Participants
n=390 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
2 Participants
n=157 Participants
|
3 Participants
n=390 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
7 Participants
n=157 Participants
|
14 Participants
n=390 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
8 Participants
n=157 Participants
|
16 Participants
n=390 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=99 Participants
|
6 participants
n=107 Participants
|
6 participants
n=206 Participants
|
15 participants
n=157 Participants
|
30 participants
n=390 Participants
|
PRIMARY outcome
Timeframe: 9 weeksThe determination of the dose limiting toxicity as defined by The National Cancer Institute Common Toxicity Criteria version 3 as follows: grade 4 neutropenia \>5 days; grade 3/4 febrile neutropenia; grade 4 thrombocytopenia; or grade \>2 non-hematologic toxicities (except for nausea/vomiting, alopecia, or fatigue).
Outcome measures
| Measure |
Novel Drug Combination
n=15 Participants
There is only one arm but it incorporates two phases. Phase I utilizes a combination of bendamustine and irinotecan for Regimen A followed by etoposide and carboplatin for Regimen B.
Bendamustine, Irinotecan, Etoposide/Carboplatin (Novel drug combination): Subjects will be treated with irinotecan (150 mg/m2) infusion on Day 1 followed by infusion of bendamustine on Days 1 and 2 at increasing dose levels using a 3+3 design (starting dose of 80-mg/m2/d with 20 mg/mg/d incremental increase to max 120 mg/m2/d) (Regimen A). This will be repeated every 3 weeks for a total of 3 cycles. Restaging for response will be performed prior to the next regimen.
* All subjects will then be given carboplatin (AUC 6) on day 1 and etoposide (100 mg/m2) on days 1, 2 and 3 (Regimen B). They will receive 3 cycles of this regimen every 3 weeks prior to restaging.
* At the end (3 weeks after) of the sixth total round of chemotherapy, subjects will be re-evaluated for response, and will be followed
|
|---|---|
|
Number of Participants Experiencing Dose Limiting Toxicity Regimen A - Phase I
Phase I - Cohort I
|
0 participants
|
|
Number of Participants Experiencing Dose Limiting Toxicity Regimen A - Phase I
Phase I - Cohort II
|
1 participants
|
|
Number of Participants Experiencing Dose Limiting Toxicity Regimen A - Phase I
Phase I - Cohort III
|
1 participants
|
PRIMARY outcome
Timeframe: 9 weeksThe degree of toxicity as defined by The National Cancer Institute Common Toxicity Criteria version 3.
Outcome measures
| Measure |
Novel Drug Combination
n=15 Participants
There is only one arm but it incorporates two phases. Phase I utilizes a combination of bendamustine and irinotecan for Regimen A followed by etoposide and carboplatin for Regimen B.
Bendamustine, Irinotecan, Etoposide/Carboplatin (Novel drug combination): Subjects will be treated with irinotecan (150 mg/m2) infusion on Day 1 followed by infusion of bendamustine on Days 1 and 2 at increasing dose levels using a 3+3 design (starting dose of 80-mg/m2/d with 20 mg/mg/d incremental increase to max 120 mg/m2/d) (Regimen A). This will be repeated every 3 weeks for a total of 3 cycles. Restaging for response will be performed prior to the next regimen.
* All subjects will then be given carboplatin (AUC 6) on day 1 and etoposide (100 mg/m2) on days 1, 2 and 3 (Regimen B). They will receive 3 cycles of this regimen every 3 weeks prior to restaging.
* At the end (3 weeks after) of the sixth total round of chemotherapy, subjects will be re-evaluated for response, and will be followed
|
|---|---|
|
Number of Patients With Adverse Events - Phase II
|
8 participants
|
SECONDARY outcome
Timeframe: 7 monthsUsing the Response Evaluation Criteria in Solid Tumors (RECIST 2000), progression is defined as 20% or greater increase from the baseline tumor parameters or new lesions.
Outcome measures
| Measure |
Novel Drug Combination
n=27 Participants
There is only one arm but it incorporates two phases. Phase I utilizes a combination of bendamustine and irinotecan for Regimen A followed by etoposide and carboplatin for Regimen B.
Bendamustine, Irinotecan, Etoposide/Carboplatin (Novel drug combination): Subjects will be treated with irinotecan (150 mg/m2) infusion on Day 1 followed by infusion of bendamustine on Days 1 and 2 at increasing dose levels using a 3+3 design (starting dose of 80-mg/m2/d with 20 mg/mg/d incremental increase to max 120 mg/m2/d) (Regimen A). This will be repeated every 3 weeks for a total of 3 cycles. Restaging for response will be performed prior to the next regimen.
* All subjects will then be given carboplatin (AUC 6) on day 1 and etoposide (100 mg/m2) on days 1, 2 and 3 (Regimen B). They will receive 3 cycles of this regimen every 3 weeks prior to restaging.
* At the end (3 weeks after) of the sixth total round of chemotherapy, subjects will be re-evaluated for response, and will be followed
|
|---|---|
|
Progression Free Survival
|
6.0 months
Interval 4.0 to 7.0
|
Adverse Events
Novel Drug Combination
Serious events: 15 serious events
Other events: 15 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Novel Drug Combination
n=30 participants at risk
This novel drug combination includes: Bendamustine, Irinotecan, and Etoposide/Carboplatin.This study has only one arm but it incorporates two phases. Phase I utilizes a combination of bendamustine and irinotecan for Regimen A followed by etoposide and carboplatin for Regimen B.
Novel Drug Combination: This novel drug combination includes: Bendamustine, Irinotecan, and Etoposide/Carboplatin. Subjects will be treated with irinotecan (150 mg/m2) infusion on Day 1 followed by infusion of bendamustine on Days 1 and 2 at increasing dose levels using a 3+3 design (starting dose of 80-mg/m2/d with 20 mg/mg/d incremental increase to max 120 mg/m2/d) (Regimen A). This will be repeated every 3 weeks for a total of 3 cycles. Restaging for response will be performed prior to the next regimen.
•All subjects will then be given carboplatin (AUC 6) on day 1 and etoposide (100 mg/m2) on days 1, 2 and 3 (Regimen B). They will receive 3 cycles of this regimen every 3 weeks prior to restaging.
|
|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
50.0%
15/30 • Number of events 15 • 9 Weeks
|
|
Gastrointestinal disorders
Diarrhea
|
50.0%
15/30 • Number of events 15 • 9 Weeks
|
|
General disorders
Fatigue
|
33.3%
10/30 • Number of events 10 • 9 Weeks
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
20.0%
6/30 • Number of events 6 • 9 Weeks
|
|
Metabolism and nutrition disorders
Hyponatremia
|
6.7%
2/30 • Number of events 2 • 9 Weeks
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
3.3%
1/30 • Number of events 1 • 9 Weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
3.3%
1/30 • Number of events 1 • 9 Weeks
|
|
Infections and infestations
Febrile Neutropenia
|
13.3%
4/30 • Number of events 4 • 9 Weeks
|
Other adverse events
| Measure |
Novel Drug Combination
n=30 participants at risk
This novel drug combination includes: Bendamustine, Irinotecan, and Etoposide/Carboplatin.This study has only one arm but it incorporates two phases. Phase I utilizes a combination of bendamustine and irinotecan for Regimen A followed by etoposide and carboplatin for Regimen B.
Novel Drug Combination: This novel drug combination includes: Bendamustine, Irinotecan, and Etoposide/Carboplatin. Subjects will be treated with irinotecan (150 mg/m2) infusion on Day 1 followed by infusion of bendamustine on Days 1 and 2 at increasing dose levels using a 3+3 design (starting dose of 80-mg/m2/d with 20 mg/mg/d incremental increase to max 120 mg/m2/d) (Regimen A). This will be repeated every 3 weeks for a total of 3 cycles. Restaging for response will be performed prior to the next regimen.
•All subjects will then be given carboplatin (AUC 6) on day 1 and etoposide (100 mg/m2) on days 1, 2 and 3 (Regimen B). They will receive 3 cycles of this regimen every 3 weeks prior to restaging.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
16.7%
5/30 • Number of events 5 • 9 Weeks
|
|
Blood and lymphatic system disorders
Neutropenia
|
3.3%
1/30 • Number of events 1 • 9 Weeks
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
6.7%
2/30 • Number of events 2 • 9 Weeks
|
|
Gastrointestinal disorders
Nausea & Vomiting
|
33.3%
10/30 • Number of events 10 • 9 Weeks
|
|
Gastrointestinal disorders
Diarrhea
|
36.7%
11/30 • Number of events 11 • 9 Weeks
|
|
General disorders
Fatigue
|
50.0%
15/30 • Number of events 15 • 9 Weeks
|
|
Nervous system disorders
Neuropathy
|
10.0%
3/30 • Number of events 3 • 9 Weeks
|
|
Metabolism and nutrition disorders
HyperKalemia
|
3.3%
1/30 • Number of events 1 • 9 Weeks
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
3.3%
1/30 • Number of events 1 • 9 Weeks
|
Additional Information
Francisco Robert, MD, Department of Medicine, Division of Hematology and Oncology
Univeristy of Alabama at Birmingham
Phone: 205-934-5077
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place