Metastatic Colorectal CancerPhase 1/2NCT06202001
Irinotecan, TAS-102 Plus Bevacizumab as a Second-Line Therapy in mCRC Patients
A Phase 1/2 study testing Irinotecan, Trifluridine/tipiracil (TAS-102) plus Bevacizumab in people with Metastatic Colorectal Cancer, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 1 site in China.
Trial summary
In mCRC, response to second-line chemotherapy is limited, and few treatment options are available. It is urgent to design an optimal second-line treatment regimen to improve the response rate and prolong the survival of patients with mCRC. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Irinotecan, Trifluridine/tipiracil (TAS-102) plus Bevacizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteChina
- Study dates
- 1 Oct 2022to 30 Sep 2026
- Phase
- Phase 1/2
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Colorectal adenocarcinoma confirmed histologically or histopathologically.
- Patients were clinically diagnosed with metastatic colorectal cancer based on computed tomography (CT) scan and magnetic resonance imaging (MRI) according to AJCC 8th edition.
- Patients have received oxaliplatin-based first-line chemotherapy with or without targeted therapy, immunotherapy or radiotherapy.
- Age ≥18 and ≤70.
- ECOG physical status score is 0 or 1, and no obvious deterioration within 2 weeks prior to use on Day 1 of Cycle 1.
- Appropriate organ function according to the following laboratory test values:
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- Hemoglobin value ≥90g/L.
- White blood cell count ≥3.5*109/L.
- Absolute neutrophil count ≥1.5*109/L.
- Platelet count ≥100*109/L.
- Serum creatinine ≤ upper limit of normal (ULN) or creatinine clearance ≥60ml/min.
- Total serum bilirubin ≤1.5* upper normal limit (ULN).
- Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤2.5* upper limit of normal value (ULN).
- Signed the informed consent.
Who cannot join
- The pathological types were squamous carcinoma, neuroendocrine carcinoma, adenosquamous carcinoma, and other histological types except adenocarcinoma.
- Patients who had shown hypersensitivity to Irinotecan and Trifluridine/tipiracil (TAS-102) or any other component of them. Patients who previously received irinotecan while disease progressed. However, patients who previously received irinotecan while progressing during maintenance therapy are eligible.
- Known hypersensitivity to Bevacizumab or hypersensitivity to any other component of Bevacizumab.
- Patients unable to swallow or lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication.
- Patients had recurrent episodes of bleeding (risk of gastrointestinal bleeding) or received transfusions in the previous 2 weeks.
- Major surgery in the previous 4 weeks. (Biopsy is excluded)
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- Previous or concurrent cancer diagnosed within 5 years prior to study inclusion, except for curatively treated in situ cervical cancer, non-melanoma skin cancer, basal cell carcinoma, benign prostate cancer, ductal carcinoma in situ, well-differentiated thyroid cancers and superficial bladder tumors: staged Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor with lamina propria invasion). Carcinomas that can be cured by adequate treatment are also excluded.
- History of abdominal fistula, gastro-intestinal perforation, intestinal obstruction, chronic diarrhea or inflammatory bowel disease including Crohns disease and ulcerative colitis within 6 months prior to the first study treatment.
- Patients with severe cardiac dysfunction, such as LVEF< 50%, CHF≥ grade 2, severe/unstable angina, history of stroke or transient ischemic attack or myocardial infarction in the previous 6 months.
- Uncontrolled hypertension (systolic blood pressure >160 mmHg or diastolic pressure >100 mmHg despite treatment) and uncontrolled diabetes (fasting plasma glucose > 8.9 mmol/l).
- Patients with a history of ventricular tachycardia, torsades de pointes, prolonged QTc, complete left bundle branch block or third-degree atrioventricular conduction block.
- Patients with active hepatitis B, hepatitis C, syphilis or human immunodeficiency virus infection.
- Arterial or venous thrombotic or embolic events such as deep vein thrombosis, and pulmonary embolism within 3 months of starting study treatment (catheter-related thrombosis is excluded).
- Patients with active pulmonary tuberculosis were taking anti-tuberculosis treatment or have taken anti-tuberculosis treatment within 12 months of starting study treatment.
- Patients with severe primary respiratory diseases, interstitial lung disease, or history of pneumonitis.
- Patients with current active infections requiring anti-infection treatment within 2 weeks of starting study treatment.
- Patients with a history of psychiatric drug abuse or a history of drug abuse.
- Pregnant or lactating women.
- Patients of childbearing potential are unwilling to practice contraception.
- Patients with any clinically significant disease, metabolic disorders or laboratory abnormality. Investigator could reasonably consider those patients not suitable for the study, affecting the results analysis or putting those patients at high risk.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Cancer Hospital, Chinese Academy of Medical Sciences
Beijing
Yongkun Sun, 13141276041, hsunyk@126.com
About this study
Official title: Phase I/II Study of Irinotecan Plus Trifluridine/Tipiracil (TAS-102) in Combination With Bevacizumab as a Second-Line Therapy for Patients With Metastatic Colorectal Cancer (mCRC)
In mCRC, response to second-line chemotherapy is limited, and few treatment options are available. It is urgent to design an optimal second-line treatment regimen to improve the response rate and prolong the survival of patients with mCRC. Several studies preliminarily demonstrated that irinotecan, TAS-102 plus bevacizumab regimen could bring promising efficacy with a tolerable safety profile for patients with mCRC as a second-line treatment. This phase I/II study was aimed to determine the recommended phase II dose (RP2D) of the combination of TAS-102, irinotecan, and bevacizumab for future clinical trials in patients with mCRC refractory to both fluoropyrimidine and oxaliplatin and to evaluate its safety and preliminary efficacy.
Read the detailed description
This was a single-arm, open-label, phase I, dose-escalation study to establish the recommended phase II dose (RP2D) for the combination of TAS-102, irinotecan, and bevacizumab and evaluate its safety.
This study followed a classic 3+3 design, in which patients received escalating doses of TAS-102 (20, 25, 30, or 35 mg/m2/dose, administered twice daily for days 1-5) and irinotecan (135, 150, 165, or 180 mg/m2 on day 1) with a fixed dose of bevacizumab (5 mg/kg on day 1), repeated every 14 days. Initially, three patients will receive therapy at dose level 1. If dose-limiting toxicity (DLT) occurred, an additional three patients were enrolled at the same dose level. If none of the first three patients or less than two of the six patients exhibited DLT, then the study regimen was escalated to a higher dose level. If two or more DLTs occurred, the study regimen was reduced to a lower dose level.
The maximum tolerated dose (MTD) was defined as the highest dose level at which less than one-third of evaluable patients treated had a DLT during the first or second cycle of drug administration. The RP2D was defined as the MTD. At least six patients at the MTD or RP2D were needed to estimate these doses accurately.
Treatment was continued until RECIST-defined disease progression or clinical disease progression, unacceptable toxicity, patient request to withdraw treatment, and a treatment-free period of >30 consecutive days.
Adverse events (AEs) were graded based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
The response was assessed by the investigator according to RECIST version 1.1.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Irinotecan, Trifluridine/tipiracil (TAS-102) plus Bevacizumab
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Irinotecan, Trifluridine/tipiracil (TAS-102) plus BevacizumabDrug
Also called Irinotecan+TAS-102+Bevacizumab
This study followed a classic 3+3 design, in which patients received escalating doses of TAS-102 (20, 25, 30, or 35 mg/m2/dose, administered twice daily for days 1-5) and irinotecan (135, 150, 165, or 180 mg/m2 on day 1) with a fixed dose of bevacizumab (5 mg/kg on day 1), repeated every 14 days.
| Study group | Role | What they receive |
|---|---|---|
| Irinotecan, TAS-102 plus Bevacizumab arm | Experimental | This study followed a classic 3+3 design, in which patients received escalating doses of TAS-102 (20, 25, 30, or 35 mg/m2/dose, administered twice daily for days 1-5) and irinotecan (135, 150, 165, or 180 mg/m2 on day 1) with a fixed dose of bevacizumab (5 mg/kg on day 1), repeated every 14 days. Receives: Drug: Irinotecan, Trifluridine/tipiracil (TAS-102) plus Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
The proportion of patients with a confirmed complete response or partial response using RECIST 1.1
Measured: 36 months
Secondary outcomes (3)
Progression-Free Survival (PFS)
The time from the date of the first administration of this regimen to the date of first documented disease progression or death due to any cause
Measured: 36 months
Overall Survival (OS)
The time from the initiation of the first dose of medication in a patient to death from any cause.
Measured: 36 months
Safety and tolerability by incidence, severity and outcome of adverse events
Safety and tolerance will be evaluated by incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI CTC AE Version 5.0
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2024
- Study start1 Oct 2022
- Primary completion30 Sep 2025 (estimated)
- Study completion30 Sep 2026 (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 Cancer Institute and Hospital, Chinese Academy of Medical SciencesThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yongkun Sun, Study chair, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06202001
- Sponsor's protocol ID
- NCC3945
- Status last verified
- Apr 2024
- First submitted
- 2 Jan 2024
- Last updated
- 2 Apr 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Irinotecan Plus Trifluridine/Tipiracil (TAS-102) in Combination With Bevacizumab as a Second-Line Therapy for Patients With Metastatic Colorectal Cancer (mCRC)
- ClinicalTrials.gov ID
- NCT06202001
- Acronym / sponsor ID
- NCC3945
- Conditions
- Metastatic Colorectal Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Cancer Institute and Hospital, Chinese Academy of Medical SciencesUniversity, hospital or other
- Study start
- 1 Oct 2022 (actual)
- Primary completion
- 30 Sep 2025 (estimated)
- Study completion
- 30 Sep 2026 (estimated)
- First posted
- 11 Jan 2024 (actual)
- 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.
In mCRC, response to second-line chemotherapy is limited, and few treatment options are available. It is urgent to design an optimal second-line treatment regimen to improve the response rate and prolong the survival of patients with mCRC. Several studies preliminarily demonstrated that irinotecan, TAS-102 plus bevacizumab regimen could bring promising efficacy with a tolerable safety profile for patients with mCRC as a second-line treatment. This phase I/II study was aimed to determine the recommended phase II dose (RP2D) of the combination of TAS-102, irinotecan, and bevacizumab for future clinical trials in patients with mCRC refractory to both fluoropyrimidine and oxaliplatin and to evaluate its safety and preliminary efficacy.
Detailed description
This was a single-arm, open-label, phase I, dose-escalation study to establish the recommended phase II dose (RP2D) for the combination of TAS-102, irinotecan, and bevacizumab and evaluate its safety.
This study followed a classic 3+3 design, in which patients received escalating doses of TAS-102 (20, 25, 30, or 35 mg/m2/dose, administered twice daily for days 1-5) and irinotecan (135, 150, 165, or 180 mg/m2 on day 1) with a fixed dose of bevacizumab (5 mg/kg on day 1), repeated every 14 days. Initially, three patients will receive therapy at dose level 1. If dose-limiting toxicity (DLT) occurred, an additional three patients were enrolled at the same dose level. If none of the first three patients or less than two of the six patients exhibited DLT, then the study regimen was escalated to a higher dose level. If two or more DLTs occurred, the study regimen was reduced to a lower dose level.
The maximum tolerated dose (MTD) was defined as the highest dose level at which less than one-third of evaluable patients treated had a DLT during the first or second cycle of drug administration. The RP2D was defined as the MTD. At least six patients at the MTD or RP2D were needed to estimate these doses accurately.
Treatment was continued until RECIST-defined disease progression or clinical disease progression, unacceptable toxicity, patient request to withdraw treatment, and a treatment-free period of >30 consecutive days.
Adverse events (AEs) were graded based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
The response was assessed by the investigator according to RECIST version 1.1.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Irinotecan, TAS-102 plus Bevacizumab arm | Experimental | Drug: Irinotecan, Trifluridine/tipiracil (TAS-102) plus BevacizumabThis study followed a classic 3+3 design, in which patients received escalating doses of TAS-102 (20, 25, 30, or 35 mg/m2/dose, administered twice daily for days 1-5) and irinotecan (135, 150, 165, or 180 mg/m2 on day 1) with a fixed dose of bevacizumab (5 mg/kg on day 1), repeated every 14 days. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Colorectal adenocarcinoma confirmed histologically or histopathologically.
- Patients were clinically diagnosed with metastatic colorectal cancer based on computed tomography (CT) scan and magnetic resonance imaging (MRI) according to AJCC 8th edition.
- Patients have received oxaliplatin-based first-line chemotherapy with or without targeted therapy, immunotherapy or radiotherapy.
- Age ≥18 and ≤70.
- ECOG physical status score is 0 or 1, and no obvious deterioration within 2 weeks prior to use on Day 1 of Cycle 1.
Key exclusion criteria (20 listed)
- The pathological types were squamous carcinoma, neuroendocrine carcinoma, adenosquamous carcinoma, and other histological types except adenocarcinoma.
- Patients who had shown hypersensitivity to Irinotecan and Trifluridine/tipiracil (TAS-102) or any other component of them. Patients who previously received irinotecan while disease progressed. However, patients who previously received irinotecan while progressing during maintenance therapy are eligible.
- Known hypersensitivity to Bevacizumab or hypersensitivity to any other component of Bevacizumab.
- Patients unable to swallow or lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication.
- Patients had recurrent episodes of bleeding (risk of gastrointestinal bleeding) or received transfusions in the previous 2 weeks.
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 |
|---|---|---|
| Irinotecan, Trifluridine/tipiracil (TAS-102) plus BevacizumabAlso: Irinotecan+TAS-102+BevacizumabThis study followed a classic 3+3 design, in which patients received escalating doses of TAS-102 (20, 25, 30, or 35 mg/m2/dose, administered twice daily for days 1-5) and irinotecan (135, 150, 165, or 180 mg/m2 on day 1) with a fixed dose of bevacizumab (5 mg/kg on day 1), repeated every 14 days. | Drug | Irinotecan, TAS-102 plus Bevacizumab arm |
Primary outcome
Objective Response Rate (ORR)
Time frame: 36 months
The proportion of patients with a confirmed complete response or partial response using RECIST 1.1
3 secondary outcomes
Progression-Free Survival (PFS)
Time frame: 36 months
Overall Survival (OS)
Time frame: 36 months
Safety and tolerability by incidence, severity and outcome of adverse events
Time frame: 36 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2024.
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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.
Yongkun Sun study chair
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Irinotecan, Trifluridine/tipiracil (TAS-102) plus Bevacizumab in people with Metastatic Colorectal Cancer, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 1 site 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 14 inclusion and 20 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 2 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Yongkun Sun (+8613141276041, hsunyk@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: 36 months). 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 2 Apr 2024.