Metastatic Colorectal CancerPhase 1NCT02453464
A Phase Ib Study of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab) Injection Plus FOLFIRI in Chinese Patients With Metastatic Colorectal Cancer
A Phase 1 study testing Sevacizumab, Irinotecan and 5-FU in people with Metastatic Colorectal Cancer, run by Jiangsu Simcere Pharmaceutical Co., Ltd. at 3 sites in China.
Trial summary
This is an open-label, multicenter, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab) Injection in combination with FOLFIRI in patients with previously treated metastatic colorectal cancer. This study includes two stages. Read more about this study
- Who is it for?
- Ages 18 to 74 years
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Sevacizumab, Irinotecan and 5-FU
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 3 sitesChina
- Study dates
- Aug 2015to Dec 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histological/cytological confirmed unresectable metastatic colorectal cancer patients who have failed first-line oxaliplatin-based chemotherapy
- At least one measurable lesion (according to RECIST 1.1 )
- At least 4 weeks from the last chemotherapy. If patients received anti-tumor biological products, at least four t1/2 of washout period is needed
- Toxicity from previous treatment has to restore to ≤ grade 1 (NCI CTC4.0)
- ECOG performance status 0-1
- Life expectancy ≥ 3 months
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- Adequate hematologic function: ANC ≥ 1.5 × 10^9 /L, HB ≥ 90 g /L (blood transfusion allowed), PLT ≥ 100 ×10^9 /L; Adequate hepatic function: ALT ≤ 2.5 × ULN, AST ≤ 2.5 × ULN, TBIL ≤ 1.5 × ULN (patients with liver metastases ALT ≤ 5 × ULN, AST ≤ 5 × ULN); Adequate renal function: creatinine ≤ 1 × ULN; Coagulation function: INR ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN
- Patients of childbearing potential (male and female) must agree to use reliable methods of contraception until at least 12 weeks after the last dose
- Patients signed written inform consent
- Willingness and capability to communicate with investigators and to comply with protocol requirements
Who cannot join
- HCV, TP or HIV antibody positive
- Previously received anti-VEGF protein drugs, such as Bevacizumab,Sevacizumab
- Previously treated with irinotecan
- History of dihydropyrimidine dehydrogenase deficiency
- Patients with alcohol or drug dependence
- Participation in other clinical trials within 4 weeks before enrollment
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- Active or chronic hepatitis B infection with HBV DNA > 1.0 * 10^3 IU/mL
- Serious infection requiring intravenous antibiotic therapy
- Symptomatic brain metastases
- Patients with proteinuria at screening (urine protein ≥ 1+)
- History of abdominal fistula, gastrointestinal perforation, abdominal abscess within 6 months prior to enrollment
- History of intestinal obstruction, inflammatory bowel disease, or other intestinal diseases with chronic diarrhea as the major symptom
- Serious non-healing wounds, ulcers or fractures
- Major surgery (excluding biopsy) or significant trauma within 4 weeks prior to enrollment
- Active bleeding within 3 months prior to enrollment
- Bleeding diathesis or coagulation disorder
- History of arterial or venous thrombosis
- History of myocardial infarction or stroke within 6 months prior to enrollment
- Unstable angina, congestive heart failure, New York Heart Association (NYHA) class II heart failure, uncontrollable arrhythmia, uncontrolled hypertension
- Expected to receive surgery during the study or within 1 month after the last dose
- The investigators consider the patients are not suitable for this trial
- Pregnant and lactating women
- Known allergies to any excipient in the study drug
- Patients can not complete this study for any other reason
Trial locations and contacts
3 sites in 1 country.
China3 sites, 3 recruiting
- Recruiting
The First Bethune Hospital of Jilin University
Changchun, Jilin, 130021
Yanhua Ding
- Recruiting
The First Hospital of Zhejiang Province
Hangzhou, Zhejiang, 310003
Nong Xu
- Recruiting
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200032
Jin Li
About this study
Official title: A Phase Ib, Dose Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of Humanized Anti-VEGF Monoclonal Antibody(Sevacizumab) Injection Plus FOLFIRI in Chinese Patients With Metastatic Colorectal Cancer
This is an open-label, multicenter, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab) Injection in combination with FOLFIRI in patients with previously treated metastatic colorectal cancer. This study includes two stages. Stage 1 is the dose-escalation stage. Once the maximum tolerated dose (MTD) of Sevacizumab has been established, additional patients will be enrolled in the cohort-expansion stage (Stage 2).
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Sevacizumab, Irinotecan, 5-FU, Leucovorin
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SevacizumabDrug
escalating doses of Sevacizumab : 3mg/kg，4mg/kg，5mg/kg
IrinotecanDrug
Irinotecan: IV solution, IV over 90 minutes, 180 mg/m², Every 14 days, Until disease progression/toxicity
5-FUDrug
5-FU: IV solution, IV bolus over 2-4 minutes, 400 mg/m²; IV infusion over 46 hours, 2400 mg/m²; Every 14 days, Until disease progression/toxicity
LeucovorinDrug
Leucovorin: IV solution, IV over 2 hours, 400 mg/m², Every 14 days, Until disease progression/toxicity
| Study group | Role | What they receive |
|---|---|---|
| Sevacizumab+FOLFIRI | Experimental | Two weeks as one cycle. Cycle 1: FOLFIRI on day1-2, Sevacizumab on day3; Cycle 2 and after: Sevacizumab on day 1, and then FOLFIRI on day1-2 Receives: Drug: Sevacizumab; Drug: Irinotecan; Drug: 5-FU; Drug: Leucovorin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
Measured: up to 56 days
Secondary outcomes (9)
Adverse Events (NCI-CTC 4.0)
Measured: 28 days after the last dose
Plasma pharmacokinetics (PK) parameters for Sevacizumab
Measured: Cycle 1(Day3, Day4, Day7, Day10, Day13); Cycle 2-4(Day1);Cycle 4(Day1, Day2, Day5, Day8 ,Day11)
Plasma pharmacokinetics (PK) parameters (Cmax, Tmax, AUC, T1/2) for Irinotecan and its major metabolite SN-38
Measured: Day1, Day2, Day3, Day15, Day16, Day17
Plasma pharmacokinetics (PK) parameters for 5-FU
Measured: Day1, Day3, Day15, Day17
Potential biomarkers, including VEGF and ADA
Measured: VEGF:Cycle 1(Day3, Day4, Day7, Day10, Day13); Cycle 2-4(Day1);Cycle 4(Day1, Day2, Day5, Day8, Day11); ADA : within 15 minutes before each Sevacizumab administration
Objective Response Rate (ORR)
Measured: up to 3 years from date of registration
Disease Control Rate (DCR)
Measured: up to 3 years from date of registration
Progression Free Survival (PFS)
Measured: up to 3 years from date of registration
Overall Survival (OS)
Measured: up to 3 years from date of registration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2015 (estimated)
- Study startAug 2015
- Primary completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Jiangsu Simcere Pharmaceutical Co., Ltd.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jiangsu Simcere Pharmaceutical Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jin Li, MD, Principal investigator, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02453464
- Sponsor's protocol ID
- SIM129-mCRC-01
- Status last verified
- Apr 2016
- First submitted
- 19 May 2015
- Last updated
- 20 Apr 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib, Dose Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of Humanized Anti-VEGF Monoclonal Antibody(Sevacizumab) Injection Plus FOLFIRI in Chinese Patients With Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT02453464
- Acronym / sponsor ID
- SIM129-mCRC-01
- Conditions
- Metastatic Colorectal Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Jiangsu Simcere Pharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- Aug 2015
- Primary completion
- Dec 2016 (estimated)
- First posted
- 25 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, multicenter, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab) Injection in combination with FOLFIRI in patients with previously treated metastatic colorectal cancer. This study includes two stages. Stage 1 is the dose-escalation stage. Once the maximum tolerated dose (MTD) of Sevacizumab has been established, additional patients will be enrolled in the cohort-expansion stage (Stage 2).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sevacizumab+FOLFIRI | Experimental | Drug: Sevacizumab, Drug: Irinotecan, Drug: 5-FU, Drug: LeucovorinTwo weeks as one cycle. Cycle 1: FOLFIRI on day1-2, Sevacizumab on day3; Cycle 2 and after: Sevacizumab on day 1, and then FOLFIRI on day1-2 |
Who may qualify
- Ages
- 18 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Histological/cytological confirmed unresectable metastatic colorectal cancer patients who have failed first-line oxaliplatin-based chemotherapy
- At least one measurable lesion (according to RECIST 1.1 )
- At least 4 weeks from the last chemotherapy. If patients received anti-tumor biological products, at least four t1/2 of washout period is needed
- Toxicity from previous treatment has to restore to ≤ grade 1 (NCI CTC4.0)
- ECOG performance status 0-1
Key exclusion criteria (24 listed)
- HCV, TP or HIV antibody positive
- Previously received anti-VEGF protein drugs, such as Bevacizumab,Sevacizumab
- Previously treated with irinotecan
- History of dihydropyrimidine dehydrogenase deficiency
- Patients with alcohol or drug dependence
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sevacizumabescalating doses of Sevacizumab : 3mg/kg，4mg/kg，5mg/kg | Drug | Sevacizumab+FOLFIRI |
| IrinotecanIrinotecan: IV solution, IV over 90 minutes, 180 mg/m², Every 14 days, Until disease progression/toxicity | Drug | Sevacizumab+FOLFIRI |
| 5-FU5-FU: IV solution, IV bolus over 2-4 minutes, 400 mg/m²; IV infusion over 46 hours, 2400 mg/m²; Every 14 days, Until disease progression/toxicity | Drug | Sevacizumab+FOLFIRI |
| LeucovorinLeucovorin: IV solution, IV over 2 hours, 400 mg/m², Every 14 days, Until disease progression/toxicity | Drug | Sevacizumab+FOLFIRI |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: up to 56 days
9 secondary outcomes
Adverse Events (NCI-CTC 4.0)
Time frame: 28 days after the last dose
Plasma pharmacokinetics (PK) parameters for Sevacizumab
Time frame: Cycle 1(Day3, Day4, Day7, Day10, Day13); Cycle 2-4(Day1);Cycle 4(Day1, Day2, Day5, Day8 ,Day11)
Plasma pharmacokinetics (PK) parameters (Cmax, Tmax, AUC, T1/2) for Irinotecan and its major metabolite SN-38
Time frame: Day1, Day2, Day3, Day15, Day16, Day17
Plasma pharmacokinetics (PK) parameters for 5-FU
Time frame: Day1, Day3, Day15, Day17
Potential biomarkers, including VEGF and ADA
Time frame: VEGF:Cycle 1(Day3, Day4, Day7, Day10, Day13); Cycle 2-4(Day1);Cycle 4(Day1, Day2, Day5, Day8, Day11); ADA : within 15 minutes before each Sevacizumab administration
Objective Response Rate (ORR)
Time frame: up to 3 years from date of registration
Disease Control Rate (DCR)
Time frame: up to 3 years from date of registration
Progression Free Survival (PFS)
Time frame: up to 3 years from date of registration
Overall Survival (OS)
Time frame: up to 3 years from date of registration
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2016.
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CRC
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jin Li, MD principal investigator
Fudan University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sevacizumab, Irinotecan and 5-FU in people with Metastatic Colorectal Cancer, run by Jiangsu Simcere Pharmaceutical Co., Ltd. at 3 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Haijun Li, MS (86-025-85560000 ext. 1625, lihaijun@simcere.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) (time frame: up to 56 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2016.