Refractory Metastatic Colorectal CancerPhase 3NOTABLE-308NCT06343116

Nimotuzumab Combined With Trifluridine/Tipiracil in the Treatment of Refractory Metastatic Colorectal Cancer

A Phase 3 study testing Nimotuzumab injection and Trifluridine/tipiracil in people with Refractory Metastatic Colorectal Cancer, run by Biotech Pharmaceutical Co., Ltd..

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Refractory Metastatic Colorectal Cancer
What is being tested?: Nimotuzumab injection and Trifluridine/tipiracil
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 0 participants
Where: No sites listed yet
Study dates: 3 Apr 2024to Apr 2027
Phase: Phase 3
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 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Age 18-75 years old, gender unlimited;
Histologically or cytologically confirmed diagnosis of colorectal cancer (CRC);
Metastatic colorectal cancer, disease progression after previous second-line or above standard therapy;
Efficacy of previous line therapy containing an anti-EGFR monoclonal antibody (such as panitumumab or cetuximab, etc.) with complete or partial response, or disease stable; and more than 4 months from last dose of anti-EGFR agent administered before randomization;
MSS/pMMR status detected by IHC or PCR;
RAS and BRAF wild-type status;

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ECOG Performance Status 0-1;
Measurable disease according to RECIST criteria v1.1;
Life expectancy of at least 3 months;
Adequate organ and bone marrow function, defined as follows: hemoglobin≥9.0 g/dL; absolute neutrophil count (ANC)≥1.5×10^9/L; white Blood Cell Count≥3.5×10^9/L;platelets≥100×10^9/L; serum total bilirubin (TBIL)≤1.5×ULN; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the upper limit of normal (ULN), patients with liver metastases should be ≤ 5 times the ULN; serum creatinine≤1.5×ULN or estimated creatinine clearance > 60 mL/min;
Women of childbearing age should have a negative result of serum HCG or urine pregnancy tests within 72 hours prior to randomization (Postmenopausal women who have had amenorrhea for at least 12 months are considered sterile and women known to have had tubal ligation are not required to undergo pregnancy tests) ;
Good compliance and signed informed consent.

Who cannot join

Had other malignancies within the past 5 years or at the same time (exceptions include: cured thyroid cancer, non-melanoma skin cancer, carcinoma in situ of the cervix, stage I ductal carcinoma in situ, stage I endometrial cancer or other solid tumors, and effectively treated lymphoma with no evidence of disease for more than 5 years);
Has a serious underlying medical condition that makes it impossible to safely administer the trial treatment. Including but not limited to active infections requiring systemic medication: compensatory heart failure (NYHA grade III and IV), unstable angina, and acute myocardial infarction within 3 months prior to enrollment;
Patients who received trifluridine/tipiracil or treated with EGFR monoclonal antibody or EGFR tyrosine kinase inhibitor within four months;
Known allergy to prescription or any component of the prescription used in this study;
Women who are pregnant or are breastfeeding;
Has brain metastases or any symptoms of brain metastases

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Factors that significantly affect oral drug absorption, such as dysphagia, chronic diarrhea, gastrointestinal obstruction, etc; Uncontrolled Crohn's disease or ulcerative colitis;
Participated in other clinical trials within 4 weeks;
With HIV or syphilis infection, or active hepatitis (hepatitis B, hepatitis C)
Other reasons that are not suitable to participate in this study according to the researcher's judgment.

About this study

Official title: Randomized Double-blind, Placebo-controlled, Multicenter Clinical Study of Nimotuzumab Combined With Trifluridine/Tipiracil in Third-line and Beyond for the Treatment of Metastatic Colorectal Cancer

Read the detailed description

This is a randomized, double-blind, placebo-controlled, multicenter study. The main purpose of the study is to evaluate the clinical efficacy and safety of nimotuzumab combined with trifluridine/tipiracil in third-line and beyond for the treatment of metastatic colorectal cancer (mCRC). This study planned to be divided into two parts: Part A and Part B. Part A is a dose escalation study, and two dose levels are set up in terms of the dose of nimotuzumab (dose level 1: nimotuzumab 400 mg weekly; dose level 2: nimotuzumab 600 mg weekly), while the dose of trifluridine/tipiracil remains unchanged. The aim of this part is to investigate the safety of combination therapy and ensure the dose of nimotuzumab in Part B. After completed the safety-run-in of Part A, Part B can be started. In Part B (main study), a prospective, randomized, double-blind, placebo-controlled design is proposed. Patients of this part will be stratified by tumor site (left half of colorectal vs right half of colon), age (less than 70 years old vs 70 years old or older) and number of metastases (<1 vs ≥1) and randomly divided into experimental group (nimotuzumab plus trifluridine/tipiracil) and control group (placebo plus trifluridine/tipiracil) at a ratio of 2:1. Treatment will continue until disease progression or intolerable toxicity or withdrawal of consent. In part B, the primary endpoint is overall survival (OS); the secondary endpoint included: Progression free survival (PFS), time to progress (TTP), overall response rate (ORR), disease control rate (DCR), duration of response (DoR), quality of life (QoL), etc.

Conditions: Refractory Metastatic Colorectal Cancer
Being tested: Nimotuzumab injection, Placebo, Trifluridine/tipiracil
Keywords: Nimotuzumab, trifluridine/tipiracil, metastatic colorectal cancer
Medical subject headings: Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Nimotuzumab injectionDrug
Also called Taixinsheng
Nimotuzumab will be administered weekly (dose of nimotuzumab depends on part A) until disease progression, unacceptable toxicity, withdrawal of consent or death due to any cause.
PlaceboDrug
Placebo will be administered weekly (dose of placebo depends on part A) until disease progression, unacceptable toxicity, withdrawal of consent or death due to any cause.
Trifluridine/tipiracilDrug
Trifluridine/tipiracil will be administered (35 mg/m2) twice daily, 5 days a week, with 2 days of rest, for 2 weeks, followed by a 14-day rest.

Study groups in NCT06343116
Study group	Role	What they receive
experimental group	Experimental	Nimotuzumab will be administered weekly (dose of nimotuzumab depends on part A). Trifluridine/tipiracil will be administered (35 mg/m2) twice daily, 5 days a week, with 2 days of rest, for 2 weeks, followed by a 14-day rest. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent or death due to any cause. Receives: Drug: Nimotuzumab injection; Drug: Trifluridine/tipiracil
control group	Placebo comparator	Placebo will be administered weekly (dose of placebo depends on part A). Trifluridine/tipiracil will be administered (35 mg/m2) twice daily, 5 days a week, with 2 days of rest, for 2 weeks, followed by a 14-day rest. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent or death due to any cause. Receives: Drug: Placebo; Drug: Trifluridine/tipiracil

What is being measured

The primary outcome is the main question the study is designed to answer.

overall survival (OS)
The primary endpoint is overall survival (OS, defined as from randomization to death due to any cause).
Measured: Up to 18 months
dose-limiting toxicity (DLT)
DLTs at the end of the 4 weeks' treatment in part A (safety run-in).
Measured: Up to 4 weeks for each participant in part A

Secondary outcomes (8)

Progression free survival (PFS)
PFS, defined as from randomization to disease progression or all-cause death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: Up to 18 months
time to progress (TTP)
TTP, defined as from randomization to the first observation of disease progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: Up to 18 months
overall response rate (ORR)
Objective response rate (ORR), including complete response (CR) and partial response (PR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions.
Measured: Up to 18 months
disease control rate (DCR)
Disease control rate (DCR), including complete response (CR) and partial response (PR) and stable disease(SD). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT/MRI: CR, disappearance of all target lesions; PR, at least a 30% decrease in the sum of the longest diameter of target lesions.
SD, neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (PD, defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions).
Measured: Up to 18 months
duration of response (DoR)
Duration of response (DoR) is defined as the period from the first evaluation of complete response (CR) and partial response (PR) to the first evaluation of disease progression or all-cause death.
Measured: Up to 18 months
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)
Quality of Life will be evaluated by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30). The scale assesses symptoms, functionality, and overall health status/life quality. Each item is transformed to a 0-100 scale according to a standardized scoring procedure. Higher scores indicate more severe symptoms, while in the functionality and overall health status/life quality sections, higher scores signify better conditions.
Measured: Up to 18 months
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Colorectal Cancer 29 (EORTC-QLQ-CR29)
Quality of Life will also be evaluated by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Colorectal Cancer 29 (EORTC-QLQ-CR29). EORTC-QLQ-CR29 is a supplementary questionnaire module to be employed in conjunction with the Quality of Life Questionnaire Core 30 (QLQ-C30). All of the scales and single-item measures range in score from 0 to 100. A high score for the functional scale and functional single-items represents a high level of functioning, whereas a high score for the symptom scales and symptom single-items represents a high level of symptomatology or problems.
Measured: Up to 18 months
Adverse Events
Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Measured: Up to 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

3 Apr 2024Apr 2027

First posted2 Apr 2024
Study start3 Apr 2024 (estimated)
Primary completionApr 2027 (estimated)
Study completionApr 2027 (estimated)

Why it stopped: Study withdrawn before enrollment of any participant due to a corporate strategic decision. Not related to safety or efficacy concerns.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Refractory Metastatic Colorectal CancerStudies of the same condition, open and under way.
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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06343116
Sponsor's protocol ID: BPL-Nim-CRC-3001
Acronym: NOTABLE-308
Status last verified: Sep 2026
First submitted: 18 Mar 2024
Last updated: 5 Oct 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Active, not recruitingPhase 2
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CBX-12 for the Treatment of Metastatic Chemotherapy-Refractory Microsatellite Stable Colorectal Cancer
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GFH375 Plus Cetuximab vs Investigator's Choice of Treatment in KRAS G12D-Mutant Refractory Metastatic Colorectal Cancer
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Testing the Addition of Anti-cancer Drug, ZEN003694, to the Usual Chemotherapy Treatment, Cetuximab Plus Encorafenib, for Colorectal Cancer
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All Refractory Metastatic Colorectal Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Randomized Double-blind, Placebo-controlled, Multicenter Clinical Study of Nimotuzumab Combined With Trifluridine/Tipiracil in Third-line and Beyond for the Treatment of Metastatic Colorectal Cancer
ClinicalTrials.gov ID: NCT06343116
Acronym / sponsor ID: NOTABLE-308 / BPL-Nim-CRC-3001
Conditions: Refractory Metastatic Colorectal Cancer
Keywords: Nimotuzumab, trifluridine/tipiracil, metastatic colorectal cancer
Phase: Phase 3
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Study withdrawn before enrollment of any participant due to a corporate strategic decision. Not related to safety or efficacy concerns.
Enrolment: 0 participants (actual)
Lead sponsor: Biotech Pharmaceutical Co., Ltd.University, hospital or other
Study start: 3 Apr 2024 (estimated)
Primary completion: Apr 2027 (estimated)
Study completion: Apr 2027 (estimated)
First posted: 2 Apr 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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
experimental group	Experimental	Drug: Nimotuzumab injection, Drug: Trifluridine/tipiracilNimotuzumab will be administered weekly (dose of nimotuzumab depends on part A). Trifluridine/tipiracil will be administered (35 mg/m2) twice daily, 5 days a week, with 2 days of rest, for 2 weeks, followed by a 14-day rest. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent or death due to any cause.
control group	Placebo comparator	Drug: Placebo, Drug: Trifluridine/tipiracilPlacebo will be administered weekly (dose of placebo depends on part A). Trifluridine/tipiracil will be administered (35 mg/m2) twice daily, 5 days a week, with 2 days of rest, for 2 weeks, followed by a 14-day rest. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent or death due to any cause.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

Age 18-75 years old, gender unlimited;
Histologically or cytologically confirmed diagnosis of colorectal cancer (CRC);
Metastatic colorectal cancer, disease progression after previous second-line or above standard therapy;
Efficacy of previous line therapy containing an anti-EGFR monoclonal antibody (such as panitumumab or cetuximab, etc.) with complete or partial response, or disease stable; and more than 4 months from last dose of anti-EGFR agent administered before randomization;
MSS/pMMR status detected by IHC or PCR;

Key exclusion criteria (10 listed)

Had other malignancies within the past 5 years or at the same time (exceptions include: cured thyroid cancer, non-melanoma skin cancer, carcinoma in situ of the cervix, stage I ductal carcinoma in situ, stage I endometrial cancer or other solid tumors, and effectively treated lymphoma with no evidence of disease for more than 5 years);
Has a serious underlying medical condition that makes it impossible to safely administer the trial treatment. Including but not limited to active infections requiring systemic medication: compensatory heart failure (NYHA grade III and IV), unstable angina, and acute myocardial infarction within 3 months prior to enrollment;
Patients who received trifluridine/tipiracil or treated with EGFR monoclonal antibody or EGFR tyrosine kinase inhibitor within four months;
Known allergy to prescription or any component of the prescription used in this study;
Women who are pregnant or are breastfeeding;

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
Nimotuzumab injectionAlso: TaixinshengNimotuzumab will be administered weekly (dose of nimotuzumab depends on part A) until disease progression, unacceptable toxicity, withdrawal of consent or death due to any cause.	Drug	experimental group
PlaceboPlacebo will be administered weekly (dose of placebo depends on part A) until disease progression, unacceptable toxicity, withdrawal of consent or death due to any cause.	Drug	control group
Trifluridine/tipiracilTrifluridine/tipiracil will be administered (35 mg/m2) twice daily, 5 days a week, with 2 days of rest, for 2 weeks, followed by a 14-day rest.	Drug	control group, experimental group

Primary outcome

overall survival (OS)
Time frame: Up to 18 months
The primary endpoint is overall survival (OS, defined as from randomization to death due to any cause).
dose-limiting toxicity (DLT)
Time frame: Up to 4 weeks for each participant in part A
DLTs at the end of the 4 weeks' treatment in part A (safety run-in).

8 secondary outcomes

Progression free survival (PFS)
Time frame: Up to 18 months
time to progress (TTP)
Time frame: Up to 18 months
overall response rate (ORR)
Time frame: Up to 18 months
disease control rate (DCR)
Time frame: Up to 18 months
duration of response (DoR)
Time frame: Up to 18 months
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)
Time frame: Up to 18 months
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Colorectal Cancer 29 (EORTC-QLQ-CR29)
Time frame: Up to 18 months
Adverse Events
Time frame: Up to 18 months

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2026.

Related trials for Refractory Metastatic Colorectal Cancer

Active, not recruitingPhase 2
A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer
Metastatic Colorectal Cancer
RecruitingPhase 1
Phase 1 Study Evaluating the Safety and PK of ADU-1805 in Advanced Solid Tumors
Solid Tumor, Adult, Metastatic Solid Tumor
Active, not recruitingPhase 2
CBX-12 for the Treatment of Metastatic Chemotherapy-Refractory Microsatellite Stable Colorectal Cancer
Metastatic Mismatch Repair Proficient Colorectal Carcinoma, Refractory Mismatch Repair Proficient Colorectal Carcinoma
Not yet recruitingPhase 3
GFH375 Plus Cetuximab vs Investigator's Choice of Treatment in KRAS G12D-Mutant Refractory Metastatic Colorectal Cancer
Colorectal Cancer
RecruitingPhase 1
Testing the Addition of Anti-cancer Drug, ZEN003694, to the Usual Chemotherapy Treatment, Cetuximab Plus Encorafenib, for Colorectal Cancer
Metastatic Colorectal Adenocarcinoma, Recurrent Colorectal Adenocarcinoma

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.

Lin Shen study chair

Peking University Cancer Hospital & Institute

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Nimotuzumab injection and Trifluridine/tipiracil in people with Refractory Metastatic Colorectal Cancer, run by Biotech Pharmaceutical Co., Ltd..

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 12 inclusion and 10 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: withdrawn, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

overall survival (OS) (time frame: Up to 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06343116.

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 5 Oct 2026.