A Phase 3 interventional study of Bevacizumab + FOLFIRI-3 in Metastatic Colorectal Cancer, sponsored by AryoGen Pharmed Co.. Completed at 22 sites in Iran, Islamic Republic of. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2021-01-22.
Sponsored by AryoGen Pharmed Co. · Phase 3, Interventional, and Treatment
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This is a Phase III, randomized, two arms, double-blind (patient and assessor blinded), parallel active non inferiority controlled clinical trial with a 2:1 allocation. This trial was conducted to evaluate the efficacy and safety of bevacizumab (produced by AryoGen Pharmed) plus FOLFIRI-3 compared with bevacizumab (Avastin®) plus FOLFIRI-3 in patients with metastatic colorectal cancer (mCRC). Patients who met the following criteria could be recruited to receive the mentioned intervention randomly. Inclusion criteria: male or female aged 18-75 years, mCRC verified histologically, Having one or more bi-dimensionally measurable lesions as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria, Was not felt to be amenable to curative resection, With an (ECOG) performance status of ≤ 1, Life expectancy of longer than 3 months, Adequate organ and marrow function, May have received adjuvant therapy for primary colorectal cancer provided that at least 6 months have elapsed from the time the adjuvant therapy was concluded and recurrent disease was documented, Patients with history of hypertension must be well-controlled (blood pressure less than/equal to 150/100), on a stable regimen of anti-hypertensive therapy.
This is a Phase III, randomized, two arms, double-blind (patient and assessor blinded), parallel active non inferiority controlled clinical trial with a 2:1 allocation. This trial was conducted to evaluate the efficacy and safety of bevacizumab (produced by AryoGen) plus FOLFIRI-3 compared with bevacizumab (Avastin®) plus FOLFIRI-3 in patients with metastatic colorectal cancer (mCRC). Patients who met the following criteria could be recruited to receive the mentioned intervention randomly. Inclusion criteria: male or female aged 18-75 years, mCRC verified histologically, Having one or more bi-dimensionally measurable lesions as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria, Was not felt to be amenable to curative resection, With an (ECOG) performance status of ≤ 1, Life expectancy of longer than 3 months, Adequate organ and marrow function, May have received adjuvant therapy for primary colorectal cancer provided that at least 6 months have elapsed from the time the adjuvant therapy was concluded and recurrent disease was documented, Patients with history of hypertension must be well-controlled (blood pressure less than/equal to 150/100), on a stable regimen of anti-hypertensive therapy. Exclusion criteria: Prior targeted therapy for mCRC, Radiotherapy or surgery for mCRC less than 4 weeks before random assignment, Undergone major surgical procedures or open biopsy within 28 days before the initiation of study treatment, Experienced significant traumatic injury, within 28 days before study entry, Currently using or had recently used therapeutic anticoagulants, thrombolytic therapy, chronic, daily treatment with aspirin (higher than 325 mg/daily), Proteinuria exceeding 500mg/24 h, History or presence of central nervous system metastases, Female patients who are pregnant or lactating, Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab, irinotecan, 5-FU, or leucovorin, Serious non-healing wound, ulcer, or active bone fracture, Myocardial infarction within 6 months before of study enrollment, History of stroke within 6 months before of study enrollment, Unstable symptomatic arrhythmia requiring medication, Clinically significant peripheral vascular disease, Uncontrolled diabetes; Serious active or uncontrolled infection, Inability to comply with study and/or follow-up procedures. The primary endpoint is progression-free survival and overall survival, Objective Response rate, time of treatment failures, adverse events and immunogenicity will be assessed as secondary outcomes.
6,545 studies on the registry are indexed under Colorectal Neoplasms; 1,664 are open to participants now.
This study's enrollment of 126 is above the median of 76 across 4,802 interventional studies indexed under Colorectal Neoplasms.
Browse Colorectal Neoplasms studies →AryoGen Pharmed Co. is the lead sponsor of 13 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Adequate organ and marrow function as defined below:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (AryoGen) 5 mg/kg will be administered every 2 weeks.
Drug: Bevacizumab + FOLFIRI-3
Bevacizumab+FOLFIRI-3 (irinotecan, leucovorin, and 5-FU). Bevacizumab (Avastin®) 5 mg/kg will be administered every 2 weeks.
Drug: 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.
Also known as: FOLFIRI-3 = irinotecan + calcium folinate + 5-fluorouracil
Progression Free Survival (PFS)
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.
Time frame: 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
Overall Survival (OS)
Overall survival OS was defined as the time from date of randomization to date of death due to any cause
Time frame: Up to 12 months
Objective Response Rate
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.
Time frame: Up to 12 months
Time to Treatment Failure
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
Time frame: Up to 12 months
Incidence of the Adverse Events
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
Time frame: Up to 12 months
Number of Positive Anti-drug Antibody (ADA) Samples Among Patients (Immunogenicity)
Anti-drug antibody assessment
Time frame: Up to 12 months
| Milestone | Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) | Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) |
|---|---|---|
| Started | 82 | 44 |
| Patients receiving medication | 80 | 44 |
| Completed | 72 | 40 |
| Not completed | 10 | 4 |
| Withdrew: Protocol violation | 10 | 4 |
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.
| Day | Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) | Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) |
|---|---|---|
| Progression Free Survival (PFS) | 232 ± NA | 210 ± 12.21 |
Overall survival OS was defined as the time from date of randomization to date of death due to any cause
| Participants | Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) | Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) |
|---|---|---|
| Overall Survival (OS) | 30 | 17 |
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.
| Participants | Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) | Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) |
|---|---|---|
| Objective Response Rate | 17 | 5 |
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
| Day | Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) | Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) |
|---|---|---|
| Time to Treatment Failure | 73 ± 9.39 | 73 ± 9.12 |
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
| Participants | Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) | Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) |
|---|---|---|
| Incidence of the Adverse Events | 76 | 44 |
Anti-drug antibody assessment
| Participants | Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) | Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) |
|---|---|---|
| Number of Positive Anti-drug Antibody (ADA) Samples Among Patients (Immunogenicity) | 1 | 1 |
Collected over Up to 12 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) | 30/82 (36.6%) | 31/80 (38.8%) | 75/80 (93.8%) |
| Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) | 17/44 (38.6%) | 17/44 (38.6%) | 42/44 (95.5%) |
| Event | Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) | Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) |
|---|---|---|
| Disease progressionGeneral disorders | 25/80 | 15/44 |
| Myocardial infarctionCardiac disorders | 1/80 | 1/44 |
| SepsisInfections and infestations | 0/80 | 1/44 |
| Abdominal infectionInfections and infestations | 1/80 | 0/44 |
| Acute kidney injuryRenal and urinary disorders | 1/80 | 0/44 |
| Gastrointestinal haemorrhageGastrointestinal disorders | 1/80 | 0/44 |
| Opioid abusePsychiatric disorders | 1/80 | 0/44 |
| PerforationGeneral disorders | 1/80 | 0/44 |
| PeritonitisGastrointestinal disorders | 1/80 | 0/44 |
| PneumoniaInfections and infestations | 1/80 | 0/44 |
| Event | Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) | Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) |
|---|---|---|
| AnaemiaBlood and lymphatic system disorders | 62/80 | 37/44 |
| HyperglycaemiaEndocrine disorders | 43/80 | 28/44 |
| LeukopeniaBlood and lymphatic system disorders | 22/80 | 19/44 |
| NeutropeniaBlood and lymphatic system disorders | 25/80 | 15/44 |
| Aspartate aminotransferase increasedInvestigations | 24/80 | 9/44 |
| Alanine aminotransferase increasedInvestigations | 22/80 | 9/44 |
| ProteinuriaRenal and urinary disorders | 18/80 | 12/44 |
| International normalised ratio increasedInvestigations | 20/80 | 11/44 |
| Blood bilirubin increasedInvestigations | 10/80 | 9/44 |
| HyponatraemiaMetabolism and nutrition disorders | 8/80 | 9/44 |
| Age, Continuous(years) | Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) | Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) | Total |
|---|---|---|---|
| Mean | 56.26 ± 11.94 | 56.27 ± 13.12 | 56.26 ± 12.31 |
| Sex: Female, Male(Participants) | Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) | Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) | Total |
|---|---|---|---|
| Female | 31 | 15 | 46 |
| Male | 51 | 29 | 80 |
| Race (NIH/OMB)(Participants) | Bevacizumab + FOLFIRI-3 (AryoGen Pharmed Bevacizumab) | Bevacizumab + FOLFIRI-3 (Roche Bevacizumab) | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 82 | 44 | 126 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Oct 2016 to primary completion in Jul 2018, 21 months.
Results were first posted in Jan 2021, 2 years 5 months after primary completion.
Of 69 industry-sponsored phase 3 interventional studies under Colorectal Neoplasms, half reached primary completion within 43 months of starting (the median), counting those still running; a quarter within 26 and three quarters within 54. This study's 21 months is below that.
Counting every sponsor, half of 175 studies reached it within 50 months; a quarter within 35 and three quarters within 79.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Sep 2020. You cannot join it, but the record below documents what was studied.
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AryoGen Pharmed Co.