Trial Outcomes & Findings for Comparing Efficacy and Safety of Stivant (AryoGen Bevacizumab) Versus Avastin in Metastatic Colorectal Cancer (NCT NCT03288987)

Last Updated: 2021-01-22

Results Overview

PFS is defined as the time from the date of randomization to the first date of documentation progression (per investigator assessment) or death as a result of any cause.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

126 participants

Primary outcome timeframe

PFS was measured from the start of chemotherapy to the date of disease progression or to the date of death if no progression whichever came first, assessed up to 12 months

Results posted on

2021-01-22

Participant Flow

Participant milestones

Participant milestones
Measure	Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (AryoGen) 5 mg/kg will be administered every 2 weeks. Bevacizumab + FOLFIRI-3: Bevacizumab 5 mg/kg will be administered at day 1 every 2 weeks. Initially, it will be administered as a 90-min infusion. If the first infusion is well tolerated, the second will be delivered as a 60-min infusion, and if the 60-min infusion is well tolerated, all subsequent infusions will be given over 30 minutes. FOLFIRI-3 regimen consists of irinotecan 100 mg/m2 over 1 hour at day 1, leucovorin 400 mg/m2 at day 1 followed by a 46 hour 5-FU continuous infusion (2000 mg/m2) and irinotecan 100 mg/m2 over 1 hour on day 3 will administer. Induction treatment was administrated every 2 weeks until disease progression, unacceptable toxicities, surgical intervention, or withdrawal of consent.	Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (Avastin®) 5 mg/kg will be administered every 2 weeks. Bevacizumab + FOLFIRI-3: Bevacizumab 5 mg/kg will be administered at day 1 every 2 weeks. Initially, it will be administered as a 90-min infusion. If the first infusion is well tolerated, the second will be delivered as a 60-min infusion, and if the 60-min infusion is well tolerated, all subsequent infusions will be given over 30 minutes. FOLFIRI-3 regimen consists of irinotecan 100 mg/m2 over 1 hour at day 1, leucovorin 400 mg/m2 at day 1 followed by a 46 hour 5-FU continuous infusion (2000 mg/m2) and irinotecan 100 mg/m2 over 1 hour on day 3 will administer. Induction treatment was administrated every 2 weeks until disease progression, unacceptable toxicities, surgical intervention, or withdrawal of consent.
Overall Study STARTED	82	44
Overall Study Patients Receiving Medication	80	44
Overall Study COMPLETED	72	40
Overall Study NOT COMPLETED	10	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (AryoGen) 5 mg/kg will be administered every 2 weeks. Bevacizumab + FOLFIRI-3: Bevacizumab 5 mg/kg will be administered at day 1 every 2 weeks. Initially, it will be administered as a 90-min infusion. If the first infusion is well tolerated, the second will be delivered as a 60-min infusion, and if the 60-min infusion is well tolerated, all subsequent infusions will be given over 30 minutes. FOLFIRI-3 regimen consists of irinotecan 100 mg/m2 over 1 hour at day 1, leucovorin 400 mg/m2 at day 1 followed by a 46 hour 5-FU continuous infusion (2000 mg/m2) and irinotecan 100 mg/m2 over 1 hour on day 3 will administer. Induction treatment was administrated every 2 weeks until disease progression, unacceptable toxicities, surgical intervention, or withdrawal of consent.	Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (Avastin®) 5 mg/kg will be administered every 2 weeks. Bevacizumab + FOLFIRI-3: Bevacizumab 5 mg/kg will be administered at day 1 every 2 weeks. Initially, it will be administered as a 90-min infusion. If the first infusion is well tolerated, the second will be delivered as a 60-min infusion, and if the 60-min infusion is well tolerated, all subsequent infusions will be given over 30 minutes. FOLFIRI-3 regimen consists of irinotecan 100 mg/m2 over 1 hour at day 1, leucovorin 400 mg/m2 at day 1 followed by a 46 hour 5-FU continuous infusion (2000 mg/m2) and irinotecan 100 mg/m2 over 1 hour on day 3 will administer. Induction treatment was administrated every 2 weeks until disease progression, unacceptable toxicities, surgical intervention, or withdrawal of consent.
Overall Study Protocol Violation	10	4

Baseline Characteristics

Comparing Efficacy and Safety of Stivant (AryoGen Bevacizumab) Versus Avastin in Metastatic Colorectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) n=82 Participants Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (AryoGen) 5 mg/kg will be administered every 2 weeks. Bevacizumab + FOLFIRI-3: Bevacizumab 5 mg/kg will be administered at day 1 every 2 weeks. Initially, it will be administered as a 90-min infusion. If the first infusion is well tolerated, the second will be delivered as a 60-min infusion, and if the 60-min infusion is well tolerated, all subsequent infusions will be given over 30 minutes. FOLFIRI-3 regimen consists of irinotecan 100 mg/m2 over 1 hour at day 1, leucovorin 400 mg/m2 at day 1 followed by a 46 hour 5-FU continuous infusion (2000 mg/m2) and irinotecan 100 mg/m2 over 1 hour on day 3 will administer. Induction treatment was administrated every 2 weeks until disease progression, unacceptable toxicities, surgical intervention, or withdrawal of consent.	Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) n=44 Participants Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (Avastin®) 5 mg/kg will be administered every 2 weeks. Bevacizumab + FOLFIRI-3: Bevacizumab 5 mg/kg will be administered at day 1 every 2 weeks. Initially, it will be administered as a 90-min infusion. If the first infusion is well tolerated, the second will be delivered as a 60-min infusion, and if the 60-min infusion is well tolerated, all subsequent infusions will be given over 30 minutes. FOLFIRI-3 regimen consists of irinotecan 100 mg/m2 over 1 hour at day 1, leucovorin 400 mg/m2 at day 1 followed by a 46 hour 5-FU continuous infusion (2000 mg/m2) and irinotecan 100 mg/m2 over 1 hour on day 3 will administer. Induction treatment was administrated every 2 weeks until disease progression, unacceptable toxicities, surgical intervention, or withdrawal of consent.	Total n=126 Participants Total of all reporting groups
Age, Continuous	56.26 years STANDARD_DEVIATION 11.94 • n=5 Participants	56.27 years STANDARD_DEVIATION 13.12 • n=7 Participants	56.26 years STANDARD_DEVIATION 12.31 • n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	15 Participants n=7 Participants	46 Participants n=5 Participants
Sex: Female, Male Male	51 Participants n=5 Participants	29 Participants n=7 Participants	80 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	82 Participants n=5 Participants	44 Participants n=7 Participants	126 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: PFS was measured from the start of chemotherapy to the date of disease progression or to the date of death if no progression whichever came first, assessed up to 12 months

Population: The population assessable for PFS was per protocol.

PFS is defined as the time from the date of randomization to the first date of documentation progression (per investigator assessment) or death as a result of any cause.

Outcome measures

Outcome measures
Measure	Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) n=72 Participants Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (AryoGen) 5 mg/kg will be administered every 2 weeks. Bevacizumab + FOLFIRI-3: Bevacizumab 5 mg/kg will be administered at day 1 every 2 weeks. Initially, it will be administered as a 90-min infusion. If the first infusion is well tolerated, the second will be delivered as a 60-min infusion, and if the 60-min infusion is well tolerated, all subsequent infusions will be given over 30 minutes. FOLFIRI-3 regimen consists of irinotecan 100 mg/m2 over 1 hour at day 1, leucovorin 400 mg/m2 at day 1 followed by a 46 hour 5-FU continuous infusion (2000 mg/m2) and irinotecan 100 mg/m2 over 1 hour on day 3 will administer. Induction treatment was administrated every 2 weeks until disease progression, unacceptable toxicities, surgical intervention, or withdrawal of consent.	Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) n=40 Participants Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (Avastin®) 5 mg/kg will be administered every 2 weeks. Bevacizumab + FOLFIRI-3: Bevacizumab 5 mg/kg will be administered at day 1 every 2 weeks. Initially, it will be administered as a 90-min infusion. If the first infusion is well tolerated, the second will be delivered as a 60-min infusion, and if the 60-min infusion is well tolerated, all subsequent infusions will be given over 30 minutes. FOLFIRI-3 regimen consists of irinotecan 100 mg/m2 over 1 hour at day 1, leucovorin 400 mg/m2 at day 1 followed by a 46 hour 5-FU continuous infusion (2000 mg/m2) and irinotecan 100 mg/m2 over 1 hour on day 3 will administer. Induction treatment was administrated every 2 weeks until disease progression, unacceptable toxicities, surgical intervention, or withdrawal of consent.
Progression Free Survival (PFS)	232 Day Standard Error NA The median has been obtained from the KM (SPSS) using the 50th percentile and the standard error from the 45th percentile. However, it was not possible to compute the standard error (45th percentile) for AryoGen Bevacizumab because the data from the survival function did not reach the 45th percentile. This was possible for the Bevacizumab of Roche. Data should be seen in the publication of study results.	210 Day Standard Error 12.21

SECONDARY outcome

Timeframe: Up to 12 months

Population: ITT population was used in this outcome analysis. The probability of overall survival in this study was higher than 50% in one year, so the calculation of median was not applicant. The number of death in both arms is reported.

Overall survival OS was defined as the time from date of randomization to date of death due to any cause

Outcome measures

Outcome measures
Measure	Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) n=82 Participants Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (AryoGen) 5 mg/kg will be administered every 2 weeks. Bevacizumab + FOLFIRI-3: Bevacizumab 5 mg/kg will be administered at day 1 every 2 weeks. Initially, it will be administered as a 90-min infusion. If the first infusion is well tolerated, the second will be delivered as a 60-min infusion, and if the 60-min infusion is well tolerated, all subsequent infusions will be given over 30 minutes. FOLFIRI-3 regimen consists of irinotecan 100 mg/m2 over 1 hour at day 1, leucovorin 400 mg/m2 at day 1 followed by a 46 hour 5-FU continuous infusion (2000 mg/m2) and irinotecan 100 mg/m2 over 1 hour on day 3 will administer. Induction treatment was administrated every 2 weeks until disease progression, unacceptable toxicities, surgical intervention, or withdrawal of consent.	Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) n=44 Participants Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (Avastin®) 5 mg/kg will be administered every 2 weeks. Bevacizumab + FOLFIRI-3: Bevacizumab 5 mg/kg will be administered at day 1 every 2 weeks. Initially, it will be administered as a 90-min infusion. If the first infusion is well tolerated, the second will be delivered as a 60-min infusion, and if the 60-min infusion is well tolerated, all subsequent infusions will be given over 30 minutes. FOLFIRI-3 regimen consists of irinotecan 100 mg/m2 over 1 hour at day 1, leucovorin 400 mg/m2 at day 1 followed by a 46 hour 5-FU continuous infusion (2000 mg/m2) and irinotecan 100 mg/m2 over 1 hour on day 3 will administer. Induction treatment was administrated every 2 weeks until disease progression, unacceptable toxicities, surgical intervention, or withdrawal of consent.
Overall Survival (OS)	30 Participants	17 Participants

SECONDARY outcome

Timeframe: Up to 12 months

Population: Both baseline imaging and imaging at the time of withdrawal, could not be gathered in all patients. So ORR could be reported in the mentioned population in each treatment group.

Tumor response was defined as partial and complete responses, according to the RECIST criteria ( version 1.1). The definitions were as follows: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), decrease of at least 30% in the lesion that has the largest diameter; Objective Response Rate (ORR) = CR + PR.

Outcome measures

Outcome measures
Measure	Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) n=42 Participants Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (AryoGen) 5 mg/kg will be administered every 2 weeks. Bevacizumab + FOLFIRI-3: Bevacizumab 5 mg/kg will be administered at day 1 every 2 weeks. Initially, it will be administered as a 90-min infusion. If the first infusion is well tolerated, the second will be delivered as a 60-min infusion, and if the 60-min infusion is well tolerated, all subsequent infusions will be given over 30 minutes. FOLFIRI-3 regimen consists of irinotecan 100 mg/m2 over 1 hour at day 1, leucovorin 400 mg/m2 at day 1 followed by a 46 hour 5-FU continuous infusion (2000 mg/m2) and irinotecan 100 mg/m2 over 1 hour on day 3 will administer. Induction treatment was administrated every 2 weeks until disease progression, unacceptable toxicities, surgical intervention, or withdrawal of consent.	Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) n=23 Participants Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (Avastin®) 5 mg/kg will be administered every 2 weeks. Bevacizumab + FOLFIRI-3: Bevacizumab 5 mg/kg will be administered at day 1 every 2 weeks. Initially, it will be administered as a 90-min infusion. If the first infusion is well tolerated, the second will be delivered as a 60-min infusion, and if the 60-min infusion is well tolerated, all subsequent infusions will be given over 30 minutes. FOLFIRI-3 regimen consists of irinotecan 100 mg/m2 over 1 hour at day 1, leucovorin 400 mg/m2 at day 1 followed by a 46 hour 5-FU continuous infusion (2000 mg/m2) and irinotecan 100 mg/m2 over 1 hour on day 3 will administer. Induction treatment was administrated every 2 weeks until disease progression, unacceptable toxicities, surgical intervention, or withdrawal of consent.
Objective Response Rate	17 Participants	5 Participants

SECONDARY outcome

Timeframe: Up to 12 months

Time to treatment failure was defined as the time from the date of randomization to the date of each of the following, * The treatment modalities did not destroy or modify the cancer cells, * The tumor either became larger (disease progression) or stayed the same size after treatment, * Death due to any cause, * Discontinuation of treatment

Outcome measures

Outcome measures
Measure	Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) n=80 Participants Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (AryoGen) 5 mg/kg will be administered every 2 weeks. Bevacizumab + FOLFIRI-3: Bevacizumab 5 mg/kg will be administered at day 1 every 2 weeks. Initially, it will be administered as a 90-min infusion. If the first infusion is well tolerated, the second will be delivered as a 60-min infusion, and if the 60-min infusion is well tolerated, all subsequent infusions will be given over 30 minutes. FOLFIRI-3 regimen consists of irinotecan 100 mg/m2 over 1 hour at day 1, leucovorin 400 mg/m2 at day 1 followed by a 46 hour 5-FU continuous infusion (2000 mg/m2) and irinotecan 100 mg/m2 over 1 hour on day 3 will administer. Induction treatment was administrated every 2 weeks until disease progression, unacceptable toxicities, surgical intervention, or withdrawal of consent.	Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) n=44 Participants Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (Avastin®) 5 mg/kg will be administered every 2 weeks. Bevacizumab + FOLFIRI-3: Bevacizumab 5 mg/kg will be administered at day 1 every 2 weeks. Initially, it will be administered as a 90-min infusion. If the first infusion is well tolerated, the second will be delivered as a 60-min infusion, and if the 60-min infusion is well tolerated, all subsequent infusions will be given over 30 minutes. FOLFIRI-3 regimen consists of irinotecan 100 mg/m2 over 1 hour at day 1, leucovorin 400 mg/m2 at day 1 followed by a 46 hour 5-FU continuous infusion (2000 mg/m2) and irinotecan 100 mg/m2 over 1 hour on day 3 will administer. Induction treatment was administrated every 2 weeks until disease progression, unacceptable toxicities, surgical intervention, or withdrawal of consent.
Time to Treatment Failure	73 Day Standard Error 9.39	73 Day Standard Error 9.12

SECONDARY outcome

Timeframe: Up to 12 months

Population: A total of 124 patients were analyzed for AEs. since two patients did not receive study medication and were not included in the safety population.

Safety was assessed on the basis of reports of adverse events, laboratory-test results, and vital sign measurements. Adverse events were categorized According to the Common Toxicity Criteria of the National Cancer Institute, version 5.0, in which a grade of 1 indicates mild adverse events, a grade of 2 moderate adverse events, a grade of 3 serious adverse events, and a grade of 4 life-threatening adverse events

Outcome measures

Outcome measures
Measure	Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) n=80 Participants Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (AryoGen) 5 mg/kg will be administered every 2 weeks. Bevacizumab + FOLFIRI-3: Bevacizumab 5 mg/kg will be administered at day 1 every 2 weeks. Initially, it will be administered as a 90-min infusion. If the first infusion is well tolerated, the second will be delivered as a 60-min infusion, and if the 60-min infusion is well tolerated, all subsequent infusions will be given over 30 minutes. FOLFIRI-3 regimen consists of irinotecan 100 mg/m2 over 1 hour at day 1, leucovorin 400 mg/m2 at day 1 followed by a 46 hour 5-FU continuous infusion (2000 mg/m2) and irinotecan 100 mg/m2 over 1 hour on day 3 will administer. Induction treatment was administrated every 2 weeks until disease progression, unacceptable toxicities, surgical intervention, or withdrawal of consent.	Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) n=44 Participants Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (Avastin®) 5 mg/kg will be administered every 2 weeks. Bevacizumab + FOLFIRI-3: Bevacizumab 5 mg/kg will be administered at day 1 every 2 weeks. Initially, it will be administered as a 90-min infusion. If the first infusion is well tolerated, the second will be delivered as a 60-min infusion, and if the 60-min infusion is well tolerated, all subsequent infusions will be given over 30 minutes. FOLFIRI-3 regimen consists of irinotecan 100 mg/m2 over 1 hour at day 1, leucovorin 400 mg/m2 at day 1 followed by a 46 hour 5-FU continuous infusion (2000 mg/m2) and irinotecan 100 mg/m2 over 1 hour on day 3 will administer. Induction treatment was administrated every 2 weeks until disease progression, unacceptable toxicities, surgical intervention, or withdrawal of consent.
Incidence of the Adverse Events	76 Participants	44 Participants

SECONDARY outcome

Timeframe: Up to 12 months

Population: Positive ADA was reported in two patients.

Anti-drug antibody assessment

Outcome measures

Outcome measures
Measure	Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) n=82 Participants Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (AryoGen) 5 mg/kg will be administered every 2 weeks. Bevacizumab + FOLFIRI-3: Bevacizumab 5 mg/kg will be administered at day 1 every 2 weeks. Initially, it will be administered as a 90-min infusion. If the first infusion is well tolerated, the second will be delivered as a 60-min infusion, and if the 60-min infusion is well tolerated, all subsequent infusions will be given over 30 minutes. FOLFIRI-3 regimen consists of irinotecan 100 mg/m2 over 1 hour at day 1, leucovorin 400 mg/m2 at day 1 followed by a 46 hour 5-FU continuous infusion (2000 mg/m2) and irinotecan 100 mg/m2 over 1 hour on day 3 will administer. Induction treatment was administrated every 2 weeks until disease progression, unacceptable toxicities, surgical intervention, or withdrawal of consent.	Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) n=44 Participants Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (Avastin®) 5 mg/kg will be administered every 2 weeks. Bevacizumab + FOLFIRI-3: Bevacizumab 5 mg/kg will be administered at day 1 every 2 weeks. Initially, it will be administered as a 90-min infusion. If the first infusion is well tolerated, the second will be delivered as a 60-min infusion, and if the 60-min infusion is well tolerated, all subsequent infusions will be given over 30 minutes. FOLFIRI-3 regimen consists of irinotecan 100 mg/m2 over 1 hour at day 1, leucovorin 400 mg/m2 at day 1 followed by a 46 hour 5-FU continuous infusion (2000 mg/m2) and irinotecan 100 mg/m2 over 1 hour on day 3 will administer. Induction treatment was administrated every 2 weeks until disease progression, unacceptable toxicities, surgical intervention, or withdrawal of consent.
Number of Positive Anti-drug Antibody (ADA) Samples Among Patients (Immunogenicity)	1 Participants	1 Participants

Adverse Events

Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab)

Serious events: 31 serious events

Other events: 75 other events

Deaths: 30 deaths

Bevacizumab + FOLFIRI-3 (Roche Bevacizumab)

Serious events: 17 serious events

Other events: 42 other events

Deaths: 17 deaths

Serious adverse events

Serious adverse events
Measure	Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) n=80 participants at risk Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (AryoGen) 5 mg/kg will be administered every 2 weeks. Bevacizumab + FOLFIRI-3: Bevacizumab 5 mg/kg will be administered at day 1 every 2 weeks. Initially, it will be administered as a 90-min infusion. If the first infusion is well tolerated, the second will be delivered as a 60-min infusion, and if the 60-min infusion is well tolerated, all subsequent infusions will be given over 30 minutes. FOLFIRI-3 regimen consists of irinotecan 100 mg/m2 over 1 hour at day 1, leucovorin 400 mg/m2 at day 1 followed by a 46 hour 5-FU continuous infusion (2000 mg/m2) and irinotecan 100 mg/m2 over 1 hour on day 3 will administer. Induction treatment was administrated every 2 weeks until disease progression, unacceptable toxicities, surgical intervention, or withdrawal of consent.	Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) n=44 participants at risk Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (Avastin®) 5 mg/kg will be administered every 2 weeks. Bevacizumab + FOLFIRI-3: Bevacizumab 5 mg/kg will be administered at day 1 every 2 weeks. Initially, it will be administered as a 90-min infusion. If the first infusion is well tolerated, the second will be delivered as a 60-min infusion, and if the 60-min infusion is well tolerated, all subsequent infusions will be given over 30 minutes. FOLFIRI-3 regimen consists of irinotecan 100 mg/m2 over 1 hour at day 1, leucovorin 400 mg/m2 at day 1 followed by a 46 hour 5-FU continuous infusion (2000 mg/m2) and irinotecan 100 mg/m2 over 1 hour on day 3 will administer. Induction treatment was administrated every 2 weeks until disease progression, unacceptable toxicities, surgical intervention, or withdrawal of consent.
Cardiac disorders Myocardial infarction	1.2% 1/80 • Number of events 1 • Up to 12 months The Safety Population included patients who received at least one dose of the investigational medicines. The different definition of the ITT (all patients who were randomized) should explain the inconsistency across the All-cause Mortality ( ITT population: 82 patients in the group treated with Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche) and SAE/ Other AE (Safety Population: 80 patients in the group Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche).	2.3% 1/44 • Number of events 1 • Up to 12 months The Safety Population included patients who received at least one dose of the investigational medicines. The different definition of the ITT (all patients who were randomized) should explain the inconsistency across the All-cause Mortality ( ITT population: 82 patients in the group treated with Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche) and SAE/ Other AE (Safety Population: 80 patients in the group Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche).
Infections and infestations Abdominal infection	1.2% 1/80 • Number of events 1 • Up to 12 months The Safety Population included patients who received at least one dose of the investigational medicines. The different definition of the ITT (all patients who were randomized) should explain the inconsistency across the All-cause Mortality ( ITT population: 82 patients in the group treated with Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche) and SAE/ Other AE (Safety Population: 80 patients in the group Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche).	0.00% 0/44 • Up to 12 months The Safety Population included patients who received at least one dose of the investigational medicines. The different definition of the ITT (all patients who were randomized) should explain the inconsistency across the All-cause Mortality ( ITT population: 82 patients in the group treated with Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche) and SAE/ Other AE (Safety Population: 80 patients in the group Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche).
Renal and urinary disorders Acute kidney injury	1.2% 1/80 • Number of events 1 • Up to 12 months The Safety Population included patients who received at least one dose of the investigational medicines. The different definition of the ITT (all patients who were randomized) should explain the inconsistency across the All-cause Mortality ( ITT population: 82 patients in the group treated with Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche) and SAE/ Other AE (Safety Population: 80 patients in the group Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche).	0.00% 0/44 • Up to 12 months The Safety Population included patients who received at least one dose of the investigational medicines. The different definition of the ITT (all patients who were randomized) should explain the inconsistency across the All-cause Mortality ( ITT population: 82 patients in the group treated with Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche) and SAE/ Other AE (Safety Population: 80 patients in the group Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche).
General disorders Disease progression	31.2% 25/80 • Number of events 25 • Up to 12 months The Safety Population included patients who received at least one dose of the investigational medicines. The different definition of the ITT (all patients who were randomized) should explain the inconsistency across the All-cause Mortality ( ITT population: 82 patients in the group treated with Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche) and SAE/ Other AE (Safety Population: 80 patients in the group Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche).	34.1% 15/44 • Number of events 15 • Up to 12 months The Safety Population included patients who received at least one dose of the investigational medicines. The different definition of the ITT (all patients who were randomized) should explain the inconsistency across the All-cause Mortality ( ITT population: 82 patients in the group treated with Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche) and SAE/ Other AE (Safety Population: 80 patients in the group Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche).
Gastrointestinal disorders Gastrointestinal haemorrhage	1.2% 1/80 • Number of events 1 • Up to 12 months The Safety Population included patients who received at least one dose of the investigational medicines. The different definition of the ITT (all patients who were randomized) should explain the inconsistency across the All-cause Mortality ( ITT population: 82 patients in the group treated with Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche) and SAE/ Other AE (Safety Population: 80 patients in the group Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche).	0.00% 0/44 • Up to 12 months The Safety Population included patients who received at least one dose of the investigational medicines. The different definition of the ITT (all patients who were randomized) should explain the inconsistency across the All-cause Mortality ( ITT population: 82 patients in the group treated with Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche) and SAE/ Other AE (Safety Population: 80 patients in the group Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche).
Psychiatric disorders Opioid abuse	1.2% 1/80 • Number of events 1 • Up to 12 months The Safety Population included patients who received at least one dose of the investigational medicines. The different definition of the ITT (all patients who were randomized) should explain the inconsistency across the All-cause Mortality ( ITT population: 82 patients in the group treated with Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche) and SAE/ Other AE (Safety Population: 80 patients in the group Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche).	0.00% 0/44 • Up to 12 months The Safety Population included patients who received at least one dose of the investigational medicines. The different definition of the ITT (all patients who were randomized) should explain the inconsistency across the All-cause Mortality ( ITT population: 82 patients in the group treated with Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche) and SAE/ Other AE (Safety Population: 80 patients in the group Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche).
General disorders Perforation	1.2% 1/80 • Number of events 1 • Up to 12 months The Safety Population included patients who received at least one dose of the investigational medicines. The different definition of the ITT (all patients who were randomized) should explain the inconsistency across the All-cause Mortality ( ITT population: 82 patients in the group treated with Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche) and SAE/ Other AE (Safety Population: 80 patients in the group Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche).	0.00% 0/44 • Up to 12 months The Safety Population included patients who received at least one dose of the investigational medicines. The different definition of the ITT (all patients who were randomized) should explain the inconsistency across the All-cause Mortality ( ITT population: 82 patients in the group treated with Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche) and SAE/ Other AE (Safety Population: 80 patients in the group Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche).
Gastrointestinal disorders Peritonitis	1.2% 1/80 • Number of events 1 • Up to 12 months The Safety Population included patients who received at least one dose of the investigational medicines. The different definition of the ITT (all patients who were randomized) should explain the inconsistency across the All-cause Mortality ( ITT population: 82 patients in the group treated with Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche) and SAE/ Other AE (Safety Population: 80 patients in the group Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche).	0.00% 0/44 • Up to 12 months The Safety Population included patients who received at least one dose of the investigational medicines. The different definition of the ITT (all patients who were randomized) should explain the inconsistency across the All-cause Mortality ( ITT population: 82 patients in the group treated with Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche) and SAE/ Other AE (Safety Population: 80 patients in the group Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche).
Infections and infestations Pneumonia	1.2% 1/80 • Number of events 1 • Up to 12 months The Safety Population included patients who received at least one dose of the investigational medicines. The different definition of the ITT (all patients who were randomized) should explain the inconsistency across the All-cause Mortality ( ITT population: 82 patients in the group treated with Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche) and SAE/ Other AE (Safety Population: 80 patients in the group Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche).	0.00% 0/44 • Up to 12 months The Safety Population included patients who received at least one dose of the investigational medicines. The different definition of the ITT (all patients who were randomized) should explain the inconsistency across the All-cause Mortality ( ITT population: 82 patients in the group treated with Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche) and SAE/ Other AE (Safety Population: 80 patients in the group Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche).
Infections and infestations Sepsis	0.00% 0/80 • Up to 12 months The Safety Population included patients who received at least one dose of the investigational medicines. The different definition of the ITT (all patients who were randomized) should explain the inconsistency across the All-cause Mortality ( ITT population: 82 patients in the group treated with Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche) and SAE/ Other AE (Safety Population: 80 patients in the group Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche).	2.3% 1/44 • Number of events 1 • Up to 12 months The Safety Population included patients who received at least one dose of the investigational medicines. The different definition of the ITT (all patients who were randomized) should explain the inconsistency across the All-cause Mortality ( ITT population: 82 patients in the group treated with Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche) and SAE/ Other AE (Safety Population: 80 patients in the group Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche).
Vascular disorders Embolism	1.2% 1/80 • Number of events 1 • Up to 12 months The Safety Population included patients who received at least one dose of the investigational medicines. The different definition of the ITT (all patients who were randomized) should explain the inconsistency across the All-cause Mortality ( ITT population: 82 patients in the group treated with Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche) and SAE/ Other AE (Safety Population: 80 patients in the group Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche).	0.00% 0/44 • Up to 12 months The Safety Population included patients who received at least one dose of the investigational medicines. The different definition of the ITT (all patients who were randomized) should explain the inconsistency across the All-cause Mortality ( ITT population: 82 patients in the group treated with Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche) and SAE/ Other AE (Safety Population: 80 patients in the group Bevacizumab AryoGen and 44 patients in the group Bevacizumab Roche).

Other adverse events

Additional Information

Dr. Nasim Anjidani (Director of Medical- Clinical Trials)

Aryogen

Phone: 009809125477964

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place