Comparison of A140 and Erbitux Combined With mfolfox6 to Evaluate Efficacy and Safety of First-line Treatment for Ras Wild-type mCRC

• ClinicalTrials.gov Identifier: NCT04835142
• Recruitment Status: Recruiting
• First Posted: April 8, 2021
• Last Update Posted: April 13, 2021
• Sponsor: Sichuan Kelun Pharmaceutical Research Institute Co., Ltd.
• Information provided by (Responsible Party): Sichuan Kelun Pharmaceutical Research Institute Co., Ltd.

Study Description

Brief Summary:

Compare the objective remission rate of A140 and Erbitux combined with mfolfox6 regimen in the first-line treatment of Ras wild-type metastatic colorectal cancer for 12 weeks

Condition or disease	Intervention/treatment	Phase
Metastatic Colorectal Cancer	Drug: Double blind control period A140; Drug: Open single period A140	Phase 3

Detailed Description:

In this study, a multicenter, randomized, double-blind, controlled trial design was used to compare the efficacy and safety of A140 or Erbitux combined with mfolfox6 regimen in the first-line treatment of Ras wild-type metastatic colorectal cancer patients

Objective to compare the 12 week objective response rate (ORR) of A140 and ebitur combined with mfolfox6 regimen in the first-line treatment of Ras wild-type metastatic colorectal cancer.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 686 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase III Clinical Study Comparison of A140 and Erbitux Combined With mfolfox6 to Evaluate Efficacy and Safety of First-line Treatment for Ras Wild-type mCRC
• Actual Study Start Date: February 24, 2021
• Estimated Primary Completion Date: August 30, 2022
• Estimated Study Completion Date: April 30, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Double blind control period; experiment arm： All eligible subjects will receive A140 in combination with mFOLFOX-6 chemotherapy regimen every 2 weeks. control arm: All eligible subjects will receive Erbitux in combination with mFOLFOX-6 chemotherapy regimen every 2 weeks.	Drug: Double blind control period A140; experiment arm： Drug A140:400 mg/m2（D1，iv）,250 mg/m2（qw，iv） Drug Oxaliplatin 85 mg/m2（D1,iv), Drug Calcium Folinate 400 mg/m2（D1,iv） Drug 5-FU 400 mg/m2（D1,iv），2400 mg/m2 (48±4h) control arm: Drug Erbitux:400 mg/m2（D1，iv）,250 mg/m2（qw，iv） Drug Oxaliplatin 85 mg/m2（D1,iv) Drug Calcium Folinate 400 mg/m2（D1,iv） Drug 5-FU 400 mg/m2（D1,iv），2400 mg/m2 (48±4h); Other Name: KL-140
Experimental: Open single period; All eligible subjects will receive A140 in combination with mFOLFOX-6 chemotherapy regimen every 2 weeks.	Drug: Open single period A140; Drug A140:400 mg/m2（D1，iv）,250 mg/m2（qw，iv） Drug Oxaliplatin 85 mg/m2（D1,iv), Drug Calcium Folinate 400 mg/m2（D1,iv） Drug 5-FU 400 mg/m2（D1,iv），2400 mg/m2 (48±4h); Other Name: KL-140

Outcome Measures

Primary Outcome Measures :

1. ORR [ Time Frame: 16 Weeks ]
   The objective tumor response rate (ORR) of colorectal cancer patients at 12 weeks based on the evaluation of the independent imaging evaluation committee, and confirmed at least 4 weeks later

Secondary Outcome Measures :

1. ORR [ Time Frame: 16 Weeks ]
   1)Based on the researcher's assessment of the objective tumor response rate (ORR) of patients with colorectal cancer after 12 weeks of medication, and confirmed at least 4 weeks later
2. Progression-free survival (PFS) [ Time Frame: PFS-1 year ]
   2)PFS within 1 year after medication based on the evaluation by the independent imaging evaluation committee and the investigator
3. Overall survival (OS) [ Time Frame: OS-1year ]
   2) OS within 1 year after medication based on the evaluation by the independent imaging evaluation committee and the investigator
4. Progression-free survival (PFS) [ Time Frame: PFS-1 year after the last patient's first dose ]
   3)Based on the researcher's assessment of PFS after 1 year of medication
5. Overall survival (OS) [ Time Frame: OS-1 year after the last patient's first dose ]
   3)Based on the researcher's assessment of OS after 1 year of medication

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Be able to understand the procedures and methods of this study, be willing to strictly abide by the clinical trial protocol to complete this trial, and sign the informed consent voluntarily
• Male or female subjects aged 18-75 years (including 18 and 75 years)
• Histologically proven diagnosis of metastatic colorectal cancer. No previous systemic chemotherapy for metastatic colorectal cancer. Patients who have completed adjuvant chemotherapy before the start of the study can be enrolled, Platinum containing chemotherapy needs to end for more than 12 months, and non platinum containing chemotherapy needs to end for more than 6 months;
• KRAS and NRAS genotypes in tumor tissues were wild type, and BRAF-V600E mutation was not found；
• At least one measurable lesion by computer tomography(CT) or magnetic resonance imaging (MRI)according to RECIST1.1 criteria (not in an irradiated area)
• Eastern Cooperative Oncology Group(ECOG)performance status of 0 or 1 at trial entry；
• Life expectancy of at least 16 weeks；

• The level of organ function before the first medication met the following requirements:

  1. Peripheral blood cell count: leukocyte count ≥ 3×10ˆ9 / L, neutrophil count ≥ 1.5× 10ˆ9 / L, platelet count ≥ 75 × 10ˆ9 / L, hemoglobin ≥ 90 g / L;
  2. Liver function: total bilirubin ≤ 1.5 ULN, Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 ULN; AST and ALT≤ 5 ULN in subjects with liver metastasis;
  3. Renal function: serum creatinine ≤ 1.5 ULN.
• Fertile subjects (male and female) were required to receive effective medical contraceptive measures until 3 months after the last study (see Annex 4 for specific contraceptive measures).

Exclusion Criteria:

• Those who are known to have an allergic reaction to any component of the study drug；
• Local treatments such as radiotherapy, radiofrequency ablation, intervention, etc or surgical procedures (excluding prior diagnostic biopsy) in the 28 days before first administration；
• Known brain metastasis and/or leptomeningeal disease；
• People with complete intestinal obstruction and incomplete intestinal obstruction requiring treatment. However, patients whose obstruction is relieved by fistula or stent placement can be included in the group;
• Active severe clinical infection (> Grade 2, NCI-CTCAE version 5.0), including active tuberculosis；
• Uncontrolled diabetes (fasting blood glucose ≥10 mmol/L), severe lung disease (such as acute lung disease, pulmonary fibrosis that affects lung function, interstitial lung disease. Except for radiation pneumonia that has recovered), liver failure；
• Clinically significant cardiovascular diseases, such as heart failure (NYHAⅢ-Ⅳ), uncontrolled coronary heart disease, cardiomyopathy, arrhythmia, hypertension (systolic blood pressure>150mmHg and/or diastolic blood pressure>100mmHg), echocardiography The figure shows the ejection fraction <50%, the history of myocardial infarction within the past two years；
• Renal replacement therapy；
• > Grade 1 Peripheral Nerve Disorder (NCI-CTCAE Version 5.0)；
• History of organ allograft, autologous stem cell transplantation, or allogeneic stem cell transplantation；
• Previous malignancy other than CRC in the last 5 years except basal cell cancer of the skin or preinvasive cancer of the cervix；
• HIV infection, hepatitis B surface antigen positive (and peripheral blood hepatitis B virus deoxynucleotide HBV DNA ≥ 1×10ˆ4 copy number/ml or ≥ 2000 IU/ml), hepatitis C virus antibody positive (and peripheral blood hepatitis C virus nucleotide HCV RNA≥ 1×10ˆ3 copies/ml or ≥ 200 IU/ml)；
• Patients with coagulation dysfunction, meet any of the following conditions: prothrombin time (PT) ≥ 1.5 ULN， thrombin time (TT) ≥ 1.5 ULN,activated partial thromboplastin time (APTT) ≥ 1.5 ULN;
• Previously treatment with VEGF pathway targeted therapy and EGFR monoclonal antibody；

• Past treatment history:

  1. Receiving other anti-tumor treatments (including anti-tumor treatments with traditional Chinese medicines, such as Aidi injection, Kanglaite injection, Kangai injection, cininobufosin, brucea javanica oil, etc.) within 4 weeks before the first administration of the study ；
  2. Long-term systemic immunotherapy, or hormone therapy for anti-tumor purposes (physiological replacement therapy, except for those with hypothyroidism who take thyroxine);
  3. Have received G-CSF, GM-CSF, whole blood or blood component transfusions within 4 weeks before the first medication of the study;
  4. Have received other experimental drugs or interventional clinical studies within 4 weeks before the first medication of the study；
• Pregnancy (confirmed by blood pregnancy test) or lactation；
• There is currently alcohol or drug dependence；
• There is a clear neurological disease or mental illness that has not been cured, including epilepsy, dementia, schizophrenia, etc；
• Adverse events of previous treatment (except for hair loss) did not return to grade 1 or below (NCI-CTCAE version 5.0)；
• The researcher believes that the patient has other factors that affect the efficacy or safety evaluation of this study

Contacts and Locations

Contacts

Contact: Jianming Xu, Professor; 13910866712; jmxu2003@yahoo.com

Contact: Nong Xu, Professor; 13515715262; xunongclinictrial@126.com

Locations

China, Beijing

307 Hospital of PLA; Recruiting

Beijing, Beijing, China, 100071

Contact: Jianming Xu, professor 13910866712 jmxu2003@163.com

307 Hospital of PLA; Not yet recruiting

Beijing, Beijing, China, 100071

Contact: Jianming Xu 010-56943977 Hjc1126@sina.com

Sponsors and Collaborators

Sichuan Kelun Pharmaceutical Research Institute Co., Ltd.

More Information

• Responsible Party: Sichuan Kelun Pharmaceutical Research Institute Co., Ltd.
• ClinicalTrials.gov Identifier: NCT04835142
• Other Study ID Numbers: KL140-Ⅲ-02-CTP
• First Posted: April 8, 2021
• Last Update Posted: April 13, 2021
• Last Verified: March 2021

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

Keywords provided by Sichuan Kelun Pharmaceutical Research Institute Co., Ltd.:

RAS wild-type; metastatic colorectal cancer

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