Cetuximab Plus Capecitabine as Maintenance Treatment in RAS and BRAF wt Metastatic Colorectal Cancer

• Status: Not yet recruiting
• Trial end date: 2024-03-30
• Target enrollment: 0
• Participant gender: All

Summary

This is an open-label, multicenter, randomized study to be conducted in Chinese patients with RAS and BRAF wild-type mCRC. Patients who have already completed 9 cycles of standard first-line induction treatment, without discontinuation for toxicity, of cetuximab or fluorouracil or oxaliplatin,, and achieved disease control (including CR/PR and SD), and are progression free at the end of Cycle 9 will be assigned to 2 maintenance treatment groups by randomization in a 1:1 ratio to receive cetuximab + capecitabine (Arm A) or cetuximab alone (Arm B). The randomization will be stratified by induction treatment response (complete response [CR]+ partial response [PR] versus stable disease [SD]) and primary tumor location (left side only versus right side). All patients from Arm A and Arm B will be treated until progressive disease, death from any cause, unacceptable toxicity or informed consent withdrawal (whichever occurs earlier).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sun Yat-sen University
• Treatments: Capecitabine; Cetuximab

Criteria

Inclusion Criteria:

1. Written informed consent prior to performance of any study procedure.

2. Patient must be ≥18 years of age, at the time of signing the informed consent.

3. Patients who have histologically or cytologically confirmed adenocarcinoma of the colon or rectum, excluding appendix carcinoma or anal canal carcinoma, with RAS and BRAF wild-type mutation status.

4. Patients who received only FOLFOX plus cetuximab as first-line induction treatment after diagnosis of mCRC.

5. Having completed FOLFOX plus cetuximab for 9 cycles as induction treatment without discontinuation for toxicity, of cetuximab or fluorouracil or oxaliplatin and achieved disease control (including CR/PR and SD) and are progression free at the start of maintenance therapy.

6. At least one measurable metastatic lesion(s) as defined by RECIST version 1.1, considered unresectable at start of maintenance therapy. Patients who achieved CR and had no measurable lesion after induction treatment can be enrolled in this study.

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

8. Life expectancy of at least 12 weeks in the opinion of the investigator.

9. Laboratory requirements

• Neutrophils ≥1.5×109/L, platelets ≥75×109/L, and hemoglobin ≥9 g/dL;

• Total bilirubin ≤1.5×upper limit of normal (ULN); aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and/or alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤2.5×ULN (≤5×ULN in case of liver metastases); alkaline phosphatase ≤2.5×ULN (≤5×ULN in case of liver metastases, ≤10×ULN in case of bone metastases); lactate dehydrogenase (LDH) <1500 U/L;

• Creatinine clearance (calculated according to Cockcroft and Gault) >60 mL/min or serum creatinine ≤1.5×ULN.

Exclusion Criteria:

1. mCRC patients with completely resectable lesions after conversion chemotherapy are excluded. In case of liver metastases, the concept of resectability must consider both the R0 resection (tumor radicality as a goal) and remaining liver function;

2. Having received chemotherapy for mCRC other than induction therapy with FOLFOX plus cetuximab, except for adjuvant therapy that has ended >9 months (oxaliplatin-based chemotherapy) or >6 months (oxaliplatin-free chemotherapy), prior to the start of the induction treatment;

3. Other concurrently active malignancies, excluding malignancies that are disease free for more than 5 years or carcinoma-in-situ deemed cured by adequate treatment;

4. Known brain metastasis or leptomeningeal metastasis. Patients with neurological symptoms should undergo brain computed tomography (CT)/ magnetic resonance imaging (MRI) to exclude metastases;

5. Unresolved toxicity greater than or equal to Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 attributed to any prior therapies (excluding anemia, alopecia, skin pigmentation). Patients with platinum induced neurotoxicity greater than or equal to CTCAE Grade 3 should be excluded;

6. Deficiency in dihydropyrimidine dehydrogenase (DPD) as manifested by medical history of fluorouracil adverse reactions;

7. Treatment with any of the following within the specified time frame prior to study drug administration

• Major surgery within 4 weeks (excluding diagnostic biopsy, the surgical incision should be fully healed prior to study drug administration);

• Radiotherapy within 4 weeks;

• Anti-cancer therapy other than protocol-specified induction therapy or participation in other clinical studies within 4 weeks;

8. Presence of other serious disease or social circumstances that precludes patient enrollment in the opinion of the investigator.