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

• ClinicalTrials.gov Identifier: NCT04262635
• Recruitment Status: Not yet recruiting
• First Posted: February 10, 2020
• Last Update Posted: February 10, 2020
• Sponsor: Sun Yat-sen University
• Information provided by (Responsible Party): Ruihua Xu, Sun Yat-sen University

Study Description

Brief 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).

Condition or disease	Intervention/treatment	Phase
Colorectal Cancer	Drug: Cetuximab, Capecitabine; Drug: Cetuximab	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 348 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III, Multicenter, Open-label, Randomized Study to Assess the Efficacy and Safety of Cetuximab Plus Capecitabine Versus Cetuximab as Maintenance Treatment Following First-line Induction Treatment With FOLFOX and Cetuximab in Chinese Patients With RAS and BRAF Wild-type Metastatic Colorectal Cancer
• Estimated Study Start Date: September 1, 2020
• Estimated Primary Completion Date: December 30, 2023
• Estimated Study Completion Date: March 30, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: ArmA Cetuximab plus Capecitabine; Maintenance therapy with Cetuximab as intravenous (IV) infusion at the dose of 500 mg/m2, given every 2 weeks (Q2W); plus capecitabine in 2-week cycles until progressive disease, death from any cause, unacceptable toxicity or informed consent withdrawal	Drug: Cetuximab, Capecitabine; Maintenance treatment ( ArmA )
Active Comparator: ArmB Cetuximab; Maintenance therapy with Cetuximab as intravenous (IV) infusion at the dose of 500 mg/m2, given every 2 weeks (Q2W) until progressive disease, death from any cause, unacceptable toxicity or informed consent withdrawal	Drug: Cetuximab; Maintenance treatment ( ArmB )

Outcome Measures

Primary Outcome Measures :

1. Efficacy: Maintenance PFS [ Time Frame: From Baseline to primary completion date, about 42 months ]
   mPFS from randomization to PD or death from any cause

Secondary Outcome Measures :

1. Number of Participants With Adverse Events During Treatment Period [ Time Frame: From Baseline to primary completion date, about 42 months ]
   AEs included SAEs and non-serious AEs. Causality to study treatment was determined by the investigator. Severity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
2. Number of Participants With Clinical Laboratory Abnormalities During Treatment Period [ Time Frame: From Baseline to primary completion date, about 42 months ]
   Clinical laboratory tests include hematology, electrolyte and clinical chemistry.
3. Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) [ Time Frame: From Baseline to primary completion date, about 42 months ]
   Quality of life is assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30. It will be evaluated at Screening, Tumor Assessment Visit and End of Treatment visit.
4. Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CR29 (EORTC QLQ-CR29) [ Time Frame: From Baseline to primary completion date, about 42 months ]
   Quality of life in patients with colorectal cancer is assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) CR29. It will be evaluated at Screening, Tumor Assessment Visit and End of Treatment visit.
5. Overall Survival [ Time Frame: From Baseline to primary completion date, about 42 months ]
   Time from randomization to death from any cause

Other Outcome Measures:

1. Change from Baseline in Mutation Status of Selected Genes tested by Next-Generation Sequencing during Treatment Period [ Time Frame: From Baseline to primary completion date, about 42 months ]
   Mutation status of selected genes (include but are not limited to KRAS, NRAS, BRAF, HER2, PI3K, NTRK, POLE, etc ) is assessed using Next-Generation Sequencing Method. It will be evaluated at Screening and End of Treatment visit with peripheral blood samples.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Dongsheng Zhang, MD; +86 20 87343795; zhangdsh@sysucc.org.cn

Contact: Ruihua Xu, MD; +86 20 87343795; xurh@sysucc.org.cn

Locations

China, Guangdong

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, China, 510060

Contact: Ruihua Xu, MD +86 20 87343795 xurh@sysucc.org.cn

Principal Investigator: Ruihua Xu, MD

Sub-Investigator: Dongsheng Zhang, MD

Sponsors and Collaborators

Sun Yat-sen University

Investigators

• Study Chair: Ruihua Xu, MD; Sun Yat-sen University

More Information

• Responsible Party: Ruihua Xu, Professor, Sun Yat-sen University
• ClinicalTrials.gov Identifier: NCT04262635
• Other Study ID Numbers: CLASSIC
• First Posted: February 10, 2020
• Last Update Posted: February 10, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Capecitabine; Cetuximab; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological