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This multicenter, randomized, controlled, phase III study is conducted to evaluate the efficacy and safety of first line mCapOX plus Cetuximab versus mFOLFOX6 plus Cetuximab for RAS/BRAF wild-type, MSS, Unresectable Left-Sided mCRC.
Study participants who meet the enrollment criteria will be randomly assigned in a 1:1 ratio to either the mCapOX + cetuximab or mFOLFOX6 + cetuximab treatment groups, and those who have achieved control of their disease (Complete response [CR] + Partial response [PR] + Stable disease [SD]) after a maximum of 12 cycles of first-line induction therapy in both groups will continue to receive Capecitabine or Capecitabine + Cetuximab maintenance therapy until disease progression or toxicity is not tolerated or informed consent is withdrawn.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A | Experimental | mCapOX (Capecitabine+Oxaliplatin) plus Cetuximab |
|
| Arm B | Active Comparator | mFOLFOX6 (Fluorouracil+Leucovorin+Oxaliplatin) plus Cetuximab |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| mCapOX plus Cetuximab | Drug | mCapOX plus Cetuximab Induction therapy:Capecitabine 1000mg/m2 po, bid, D1-7 + Oxaliplatin ivgtt 85mg/m2, D1 + Cetuximab ivgtt 500mg/m2, D1; Q2W. Up to 12 cycle, if no progression, enter maintenance therapy. Maintenance therapy: Capecitabine 1000mg/m2 po, bid, D1-7 + Cetuximab ivgtt 500mg/m2, D1; Q2W. Until disease progression or toxicity is not tolerated. Cetuximab can be discontinued alone if not tolerated. Treatment after progression of maintenance therapy: Participants have the option to accept reintroducing the first-line induction chemotherapy regimen (mCapOx or mFOLFOX6 in combination with cetuximab) or accept second-line therapy. |
| Measure | Description | Time Frame |
|---|---|---|
| Progression free survival (PFS) | Progression free survival is defined as the period from randomization to disease progress or death. Includes first-line induction therapy and maintenance therapy. | up to 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) | Defined as the proportion of participants acquired Complete response (CR) or Partial response (PR) during treatment. Based on RECIST 1.1. | 6 months |
| Disease control rate (DCR) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yuwen Zhou, M.D. | Contact | +86 15328007741 | drzhouyuwen@163.com | |
| Meng Qiu, M.D. | Contact | qiumeng@wchscu.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| West China Hospital Sichuan University | Chengdu | Sichuan | 610041 | China |
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| mFOLFOX6 plus Cetuximab | Drug | mFOLFOX6 plus Cetuximab Induction therapy:Oxaliplatin ivgtt 85mg/m2, D1 + Leucovorin ivgtt 400mg/m2, D1 + Fluorouracil iv bolus 400mg/m2, D1 + Fluorouracil 2400mg/m2 continuous infusion for 46-48h + Cetuximab ivgtt 500mg/m2, D1; Q2W. Up to 12 cycle, if no progression, enter maintenance therapy. Maintenance therapy: Capecitabine 1000mg/m2 po, bid, D1-7 + Cetuximab ivgtt 500mg/m2, D1; Q2W. Until disease progression or toxicity is not tolerated. Cetuximab can be discontinued alone if not tolerated. Treatment after progression of maintenance therapy: Participants have the option to accept reintroducing the first-line induction chemotherapy regimen (mCapOx or mFOLFOX6 in combination with cetuximab) or accept second-line therapy. |
|
Defined as the proportion of patients who acquired Complete response (CR), Partial response (PR), or Stable disease (SD) during treatment. Based on RECIST 1.1.
| 6 months |
| Time to Failure of Strategy (TFS) | Defined as the time from the date of randomization to [secondary disease progression after reintroduction of first-line induction chemotherapy following maintenance therapy disease progression] or [all-cause death]. If participants progressed on maintenance therapy after first-line induction chemotherapy without reintroduction of first-line induction chemotherapy or progressed during first-line induction chemotherapy, TFS equals PFS | up to 3 years |
| Overall Survival (OS) | Defined as the period from randomization to death from any cause | up to 5 years |
| Adverse Event rate | The rate of adverse event after treatment | up to 3 years |
| Pharmacoeconomic | Including CERs (Cost-Effectiveness Ratios) and ICERs (Incremental Cost-Effectiveness Ratios). CERs:Defined as the ratio of the total costs of a medical intervention to the health benefits gained from that intervention. ICERs:Defined as the ratio of the difference in costs between two alternative interventions(Arm A and Arm B) to the difference in their effectiveness. | up to 3 years |
| Quality of Life | Assessment of quality of life through the Quality of Life Questionnaire (QLQ) | up to 3 years |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
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| ID | Term |
|---|---|
| D000068818 | Cetuximab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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