Trial Outcomes & Findings for Study of Metformin Plus Paclitaxel/Carboplatin/Bevacizumab in Patients With Adenocarcinoma. (NCT NCT01578551)
NCT ID: NCT01578551
Last Updated: 2018-12-19
Results Overview
Number of months without evidence of progression after 1 year of the combination of metformin and standard chemotherapy in patients with previously untreated advanced or metastatic pulmonary adenocarcinoma.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
25 participants
Primary outcome timeframe
1 year
Results posted on
2018-12-19
Participant Flow
Participant milestones
| Measure |
Arm A
Metformin dose of 500 mg twice a day After one week, increase dose of metformin to 1000 mg as the first dose of the day and 500 mg as the second dose. After another week, increase to 1000 mg of metformin two times a day. Metformin tx initiated 1 week before beginning chemotherapy, chemotherapy not delayed for metformin loading.
Paclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle. Paclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy.
Carboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days
Bevacizumab: 15 mg/kg every 21 days, every 21 days until PD
|
Arm B
Paclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle.
Carboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days
Paclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy
Bevacizumab: All patients will receive the drug at 15 mg/kg every 21 days, given immediately after completion of chemotherapy, starting with Cycle 1. After induction chemotherapy is completed (4 cycles), bevacizumab will continue at 15 mg/kg every 21 days until PD (provided neither PD nor toxicity requiring discontinuation has occurred) measured from date of first dose of bevacizumab.
|
|---|---|---|
|
Overall Study
STARTED
|
19
|
6
|
|
Overall Study
COMPLETED
|
18
|
6
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Arm A
Metformin dose of 500 mg twice a day After one week, increase dose of metformin to 1000 mg as the first dose of the day and 500 mg as the second dose. After another week, increase to 1000 mg of metformin two times a day. Metformin tx initiated 1 week before beginning chemotherapy, chemotherapy not delayed for metformin loading.
Paclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle. Paclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy.
Carboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days
Bevacizumab: 15 mg/kg every 21 days, every 21 days until PD
|
Arm B
Paclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle.
Carboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days
Paclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy
Bevacizumab: All patients will receive the drug at 15 mg/kg every 21 days, given immediately after completion of chemotherapy, starting with Cycle 1. After induction chemotherapy is completed (4 cycles), bevacizumab will continue at 15 mg/kg every 21 days until PD (provided neither PD nor toxicity requiring discontinuation has occurred) measured from date of first dose of bevacizumab.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
Baseline Characteristics
Study of Metformin Plus Paclitaxel/Carboplatin/Bevacizumab in Patients With Adenocarcinoma.
Baseline characteristics by cohort
| Measure |
Arm A
n=19 Participants
Metformin starting at a dose of 500 mg twice a day, orally with meals. After one week, increase the dose of metformin to 1000 mg as the first dose of the day and 500 mg as the second dose. After another week, increase to 1000 mg of metformin two times a day. Metformin treatment will be initiated one week before beginning chemotherapy, if possible, but chemotherapy will not be delayed for metformin loading.
Paclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle.
.
Carboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days
Paclitaxel + Carbop
|
Arm B
n=6 Participants
Paclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle. Paclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy.
Carboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days
Paclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy
Bevacizumab: All patients will receive the drug at 15 mg/kg every 21 days, given immediately after completion of chemotherapy, starting with
|
Total
n=25 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
7 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
12 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Age, Continuous
|
58 years
n=5 Participants
|
64 years
n=7 Participants
|
61 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
19 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 1 yearNumber of months without evidence of progression after 1 year of the combination of metformin and standard chemotherapy in patients with previously untreated advanced or metastatic pulmonary adenocarcinoma.
Outcome measures
| Measure |
Arm A
n=18 Participants
Metformin 500 mg twice a day, orally with meals. After one week, increase 1000 mg as the first dose of the day and 500 mg as the second dose. After another week, increase to 1000 mg of metformin two times a day. Metformin treatment will be initiated one week before beginning chemotherapy, if possible, but chemotherapy will not be delayed for metformin loading.
Paclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle. Carboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days
Paclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy
Bevacizumab: 15 mg/kg every 21 days, Metformin: 1000 mg twice daily with food.
|
Arm B
n=6 Participants
Paclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle. Carboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days
Paclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy
Bevacizumab: All patients will receive the drug at 15 mg/kg every 21 days, given immediately after completion of chemotherapy, starting with Cycle 1. After induction chemotherapy is completed (4 cycles), bevacizumab will continue at 15 mg/kg every 21 days until PD (provided neither PD nor toxicity requiring discontinuation has occurred) measured from date of first dose of bevacizumab.
|
|---|---|---|
|
Progression Free Survival (PFS)
|
9.6 months
Interval 7.3 to
The upper limits for the respective 95% confidence intervals could not be computed, given the small numbers of patients and censoring pattern.
|
6.7 months
Interval 4.4 to
The upper limits for the respective 95% confidence intervals could not be computed, given the small numbers of patients and censoring pattern.
|
SECONDARY outcome
Timeframe: 2 yearsPercentage of participants with complete or partial response to combination of metformin with standard chemotherapy in patients with previously untreated advanced or metastatic pulmonary adenocarcinoma as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Outcome measures
| Measure |
Arm A
n=18 Participants
Metformin 500 mg twice a day, orally with meals. After one week, increase 1000 mg as the first dose of the day and 500 mg as the second dose. After another week, increase to 1000 mg of metformin two times a day. Metformin treatment will be initiated one week before beginning chemotherapy, if possible, but chemotherapy will not be delayed for metformin loading.
Paclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle. Carboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days
Paclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy
Bevacizumab: 15 mg/kg every 21 days, Metformin: 1000 mg twice daily with food.
|
Arm B
n=6 Participants
Paclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle. Carboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days
Paclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy
Bevacizumab: All patients will receive the drug at 15 mg/kg every 21 days, given immediately after completion of chemotherapy, starting with Cycle 1. After induction chemotherapy is completed (4 cycles), bevacizumab will continue at 15 mg/kg every 21 days until PD (provided neither PD nor toxicity requiring discontinuation has occurred) measured from date of first dose of bevacizumab.
|
|---|---|---|
|
Response to Therapy
|
56 percentage of participants
Interval 31.0 to 78.0
|
33 percentage of participants
Interval 6.0 to 76.0
|
SECONDARY outcome
Timeframe: up to 2 yearsNumber of months alive after 1 year of the combination of metformin with standard chemotherapy in patients with previously untreated advanced or metastatic pulmonary adenocarcinoma.
Outcome measures
| Measure |
Arm A
n=18 Participants
Metformin 500 mg twice a day, orally with meals. After one week, increase 1000 mg as the first dose of the day and 500 mg as the second dose. After another week, increase to 1000 mg of metformin two times a day. Metformin treatment will be initiated one week before beginning chemotherapy, if possible, but chemotherapy will not be delayed for metformin loading.
Paclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle. Carboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days
Paclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy
Bevacizumab: 15 mg/kg every 21 days, Metformin: 1000 mg twice daily with food.
|
Arm B
n=6 Participants
Paclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle. Carboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days
Paclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy
Bevacizumab: All patients will receive the drug at 15 mg/kg every 21 days, given immediately after completion of chemotherapy, starting with Cycle 1. After induction chemotherapy is completed (4 cycles), bevacizumab will continue at 15 mg/kg every 21 days until PD (provided neither PD nor toxicity requiring discontinuation has occurred) measured from date of first dose of bevacizumab.
|
|---|---|---|
|
Overall Survial
|
15.9 months
Interval 8.4 to
The upper limits for the respective 95% confidence intervals could not be computed, given the small numbers of patients and censoring pattern.
|
13.9 months
Interval 12.7 to
The upper limits for the respective 95% confidence intervals could not be computed, given the small numbers of patients and censoring pattern.
|
Adverse Events
Arm A
Serious events: 1 serious events
Other events: 19 other events
Deaths: 0 deaths
Arm B
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Arm A
n=19 participants at risk
Metformin starting at a dose of 500 mg twice a day, orally with meals. After one week, increase the dose of metformin to 1000 mg as the first dose of the day and 500 mg as the second dose. After another week, increase to 1000 mg of metformin two times a day. Metformin treatment will be initiated one week before beginning chemotherapy, if possible, but chemotherapy will not be delayed for metformin loading.
Paclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle.
Carboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days
Bevacizumab: 15 mg/kg every 21 days, Metformin: 1000 mg twice daily with food.
|
Arm B
n=6 participants at risk
Paclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle.
Carboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days
Paclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy
Bevacizumab: All patients will receive the drug at 15 mg/kg every 21 days, given immediately after completion of chemotherapy, starting with Cycle 1. After induction chemotherapy is completed (4 cycles), bevacizumab will continue at 15 mg/kg every 21 days until PD (provided neither PD nor toxicity requiring discontinuation has occurred) measured from date of first dose of bevacizumab.
|
|---|---|---|
|
Gastrointestinal disorders
Colonic perforation
|
5.3%
1/19 • Number of events 1 • up to 1 year
|
0.00%
0/6 • up to 1 year
|
Other adverse events
| Measure |
Arm A
n=19 participants at risk
Metformin starting at a dose of 500 mg twice a day, orally with meals. After one week, increase the dose of metformin to 1000 mg as the first dose of the day and 500 mg as the second dose. After another week, increase to 1000 mg of metformin two times a day. Metformin treatment will be initiated one week before beginning chemotherapy, if possible, but chemotherapy will not be delayed for metformin loading.
Paclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle.
Carboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days
Bevacizumab: 15 mg/kg every 21 days, Metformin: 1000 mg twice daily with food.
|
Arm B
n=6 participants at risk
Paclitaxel: 200 mg/m² IV over 3 hours, day 1 of each cycle.
Carboplatin: Carboplatin is administered at AUC= 6 mg/ml X min IV over 15-30 minutes, immediately following Paclitaxel infusion every 21 days
Paclitaxel + Carboplatin + Bevacizumab will be administered once every 21 days (Day 1) for up to 6 cycles. If subject has complete response, partial response, stable disease, or unacceptable toxicity. Bevacizumab with Metformin (Arm A) or Bevacizumab alone (Arm B) may continue as maintenance therapy
Bevacizumab: All patients will receive the drug at 15 mg/kg every 21 days, given immediately after completion of chemotherapy, starting with Cycle 1. After induction chemotherapy is completed (4 cycles), bevacizumab will continue at 15 mg/kg every 21 days until PD (provided neither PD nor toxicity requiring discontinuation has occurred) measured from date of first dose of bevacizumab.
|
|---|---|---|
|
Blood and lymphatic system disorders
White blood cell count decreased
|
15.8%
3/19 • Number of events 3 • up to 1 year
|
0.00%
0/6 • up to 1 year
|
|
Blood and lymphatic system disorders
Neutrophil count decreased
|
52.6%
10/19 • Number of events 10 • up to 1 year
|
33.3%
2/6 • Number of events 2 • up to 1 year
|
|
Blood and lymphatic system disorders
Lymphocyte count decreased
|
21.1%
4/19 • Number of events 4 • up to 1 year
|
16.7%
1/6 • Number of events 1 • up to 1 year
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
5.3%
1/19 • Number of events 1 • up to 1 year
|
16.7%
1/6 • Number of events 1 • up to 1 year
|
|
Infections and infestations
Sepsis
|
5.3%
1/19 • Number of events 1 • up to 1 year
|
0.00%
0/6 • up to 1 year
|
|
Infections and infestations
Appendicitis
|
0.00%
0/19 • up to 1 year
|
16.7%
1/6 • Number of events 1 • up to 1 year
|
|
Infections and infestations
Catheter-related infection
|
5.3%
1/19 • Number of events 1 • up to 1 year
|
0.00%
0/6 • up to 1 year
|
|
Blood and lymphatic system disorders
Hyponatremia
|
5.3%
1/19 • Number of events 1 • up to 1 year
|
16.7%
1/6 • Number of events 1 • up to 1 year
|
|
Blood and lymphatic system disorders
Hypokalemia
|
5.3%
1/19 • Number of events 1 • up to 1 year
|
16.7%
1/6 • Number of events 1 • up to 1 year
|
|
Blood and lymphatic system disorders
Hypophosphatemia
|
10.5%
2/19 • Number of events 2 • up to 1 year
|
0.00%
0/6 • up to 1 year
|
|
Blood and lymphatic system disorders
Hyperglycemia
|
5.3%
1/19 • Number of events 1 • up to 1 year
|
16.7%
1/6 • Number of events 1 • up to 1 year
|
|
Gastrointestinal disorders
Nausea
|
5.3%
1/19 • Number of events 1 • up to 1 year
|
0.00%
0/6 • up to 1 year
|
|
Gastrointestinal disorders
Vomiting
|
15.8%
3/19 • Number of events 3 • up to 1 year
|
0.00%
0/6 • up to 1 year
|
|
Gastrointestinal disorders
Dehydration
|
10.5%
2/19 • Number of events 2 • up to 1 year
|
16.7%
1/6 • Number of events 1 • up to 1 year
|
|
Investigations
Infusion related reaction
|
5.3%
1/19 • Number of events 1 • up to 1 year
|
33.3%
2/6 • Number of events 2 • up to 1 year
|
|
Investigations
Headache
|
5.3%
1/19 • Number of events 1 • up to 1 year
|
0.00%
0/6 • up to 1 year
|
|
Investigations
Neuropathy
|
0.00%
0/19 • up to 1 year
|
16.7%
1/6 • Number of events 1 • up to 1 year
|
|
General disorders
Arthralgia
|
5.3%
1/19 • Number of events 1 • up to 1 year
|
0.00%
0/6 • up to 1 year
|
|
General disorders
Pain in extremity
|
0.00%
0/19 • up to 1 year
|
16.7%
1/6 • Number of events 1 • up to 1 year
|
|
General disorders
Bone pain
|
5.3%
1/19 • Number of events 1 • up to 1 year
|
0.00%
0/6 • up to 1 year
|
|
Cardiac disorders
Hypertension
|
15.8%
3/19 • Number of events 3 • up to 1 year
|
0.00%
0/6 • up to 1 year
|
|
Cardiac disorders
Thomboembolic event
|
10.5%
2/19 • Number of events 2 • up to 1 year
|
0.00%
0/6 • up to 1 year
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place