Donafenib for Previously Treated Metastatic Colorectal Cancer

Efficacy and Safety of Donafenib in Patients With Previously Treated Metastatic Colorectal Cancer:a Controlled,Multicentre,Randomised, Phase 3 Trial

The investigators do the clinical trial (patients with metastatic colorectal cancer treated with donafenib/placebo after failure of standard therapy) to assess efficacy and safety of donafenib in patients with metastatic colorectal cancer, progressing after all approved standard therapies.

Study Overview

• Status: Completed
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: Donafenib; Drug: Placebo

Detailed Description

The study is a randomization,multicentre, phase 3 study recruiting 510 patients. Patients were eligible to participate when they have histological or cytological documentation of adenocarcinoma of the colon or rectum. They must have received locally and currently approved standard therapies and to have disease progression during or within 3 months after the last administration of the last standard therapy or to have stopped standard therapy because of unacceptable toxic effects. The available standard therapies have to include as many of the following as were licensed: a fluoropyrimidine,oxaliplatin,irinotecan.

All patients receive best supportive care, excluding other investigational antitumour agents or antineoplastic chemotherapy, hormonal therapy, or immunotherapy.

Patients receive oral donafenib 300mg (CM4307) on days 1-21 of each 4 weeks cycle until disease progression,death,or the unacceptable toxic effects.The primary endpoint is overall survival.The second endpoint is progression-free survival.

• Study Type: Interventional
• Enrollment (Actual): 536
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100071
      • The 307th Hospital of Chinese People's Liberation Army
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital Sichuan

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histological or cytological documentation of adenocarcinoma of the colon or rectum;

• Subjects with metastatic colorectal cancer and must have progressed during or within 3 months following the last administration of approved standard therapies which must include a fluoropyrimidine, oxaliplatin and irinotecan:

  1. Subjects treated with oxaliplatin in an adjuvant setting should have progressed during or within 6 months of completion of adjuvant therapy;
  2. Subjects who progress more than 6 months after completion of oxaliplatin containing adjuvant treatment must be retreated with oxaliplatin-based therapy to be eligible;
  3. Subjects who have withdrawn from standard treatment due to unacceptable toxicity warranting discontinuation of treatment and precluding retreatment with the same agent prior to progression of disease will also be allowed into the study;
  4. Subjects may have received prior treatment with bevacizumab and/or cetuximab/panitumumab.
• Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)].
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 1;
• Life expectancy of at least 3 months;
• Adequate bone marrow, liver and renal function as assessed by the laboratory required by protocol conducted within 7 days before randomization (platelets >80× 109/L, neutrophil > 1.5 × 109/L, Hb≥85g/L, serum creatinine ≤ 1.5×ULN, total bilirubin ≤ 1.5×ULN, and serum transaminase≤2.5×ULN or ≤5.0ULN if liver involvement);

Exclusion Criteria:

• Prior treatment with TKIs.
• Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)].
• Subjects who have no evaluable lesion except Pleural effusion, ascites or bone metastases lesion;
• Major surgery have been completed within 4 weeks before the first dose of study medicine.
• Subjects who have open wounds, active ulcers or plural stomata;
• Subjects who have completed radiotherapy or systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and hormonal therapy during this trial or within 4 weeks before the first dose of study medicine;
• Cardiological disease including Congestive heart failure, Unstable angina, Myocardial infarction, Cardiac arrhythmias requiring anti-arrhythmic therapy.
• Pleural effusion or ascites that causes respiratory compromise.
• Arterial or venous thrombotic or embolic events.
• Any history of or currently known brain metastases.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Donafenib; Donafenib 300mg bid on 1-21 days of each 28 days cycle.	Drug: Donafenib; treatment drug; Other Names: CM4307
Placebo Comparator: Placebo; Placebo 300mg bid on 1-21days of each 28 days cycle.	Drug: Placebo; Best support treatment; Other Names: Controlled

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.	From randomization of the first subject until 316 death events observed, up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	PFS was defined as the time from date of randomization to disease progression radiological or death due to any cause, whichever occurs first. Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation.	From randomization of the first subject until 316 death events observed, up to 2 years
Disease Control Rate (DCR)	DCR is defined as the percentage of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD); CR, PR, or SD had to be maintained for at least 28 days from the first demonstration of that rating)	From randomization of the first subject until 316 death events observed, up to 2 years
Safety variables will be summarized using descriptive statistics based on adverse events collection	AE evaluated by CTCAE	From randomization of the first subject until 316 death events observed, up to 2 years

Collaborators and Investigators

• Sponsor: Suzhou Zelgen Biopharmaceuticals Co.,Ltd
• Investigators: Study Chair: Bi Feng, MD, West China Hospital; Study Chair: Xu Jianming, MD, The Affiliated Hospital of Military Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2016
• Primary Completion (Actual): April 30, 2020
• Study Completion (Actual): April 30, 2020

Study Registration Dates

• First Submitted: August 12, 2016
• First Submitted That Met QC Criteria: August 12, 2016
• First Posted (Estimate): August 17, 2016

Study Record Updates

• Last Update Posted (Actual): November 29, 2022
• Last Update Submitted That Met QC Criteria: November 28, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: ZGDC3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No plan to share date of the trial