Colorectal Cancer
Conditions
Keywords
Colorectal cancer, Fruquintinib, 013
Brief summary
Fruquintinib administered at 5mg once daily in 4 weeks treatment cycle (three weeks on and one week off) was well tolerated and demonstrated encouraging preliminary clinical antitumor activity in patients with advanced Colorectal Cancer (CRC) in Phase Ib study. This study is aimed to evaluate the efficacy and safety of Fruquintinib in the treatment of patients with metastatic CRC who have progressed after metastatic CRC second line or above standard chemotherapy.
Detailed description
This is a randomized, double-blind, placebo-controlled, multicenter Phase II clinical trial to compare the efficacy and safety of Fruquintinib plus Best Supportive Care (BSC) versus placebo plus BSC in patients with metastatic colorectal cancer who have progressed after second-line or above standard chemotherapy. After checking eligibility criteria, subjects will be randomized into Fruquintinib plus BSC group (treatment group) or placebo plus BSC group (control group) in a ration of 2:1. Primary Efficacy Endpoint: Progression free survival (PFS) (According to RECIST Version 1.1). Secondary Efficacy Endpoints: Objective Response Rate (ORR), Disease Control Rate (DCR), Overall Survival (OS). Safety and tolerance will be evaluated by incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI common terminology criteria for adverse events (CTC AE) Version 4.0.
Interventions
DRUGfruquintinib
fruquintinib is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off
DRUGplacebo
Placebo is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off
Sponsors
Fudan University
Sun Yat-sen University
Hutchison Medipharma Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* ≥ 18 and ≤ 75 years of age , with ≥ 40 Kg * Histological or cytological confirmed metastatic colorectal cancer * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 * Failed 2 or more lines of chemotherapy * Adequate hepatic, renal, heart, and hematologic functions * At least one measurable lesion (larger than 10 mm in diameter by spiral CT scan) * Signed and dated informed consent. * Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure
Exclusion criteria
* Pregnant or lactating women * Any factors that influence the usage of oral administration * Central nervous system (CNS) metastasis * One of the following conditions: non-controlled hypertension, coronary artery disease, arrhythmia and heart failure * Abuse of alcohol or drugs * Less than 4 weeks from the last clinical trial - Previous treatment with VEGFR inhibition * Disability of serious uncontrolled intercurrence infection * Proteinuria ≥ 2+ (1.0g/24hr) * Evidence or a history of bleeding tendency within two months of the enrollment, regardless of seriousness * History of artery/venous thromboembolic events in 12 months, such as cerebral vascular accident (including transient ischemic attack) etc. * History of acute myocardial infarction, acute coronary syndrome or coronary artery bypass graft (CABG) in 6 months * Bone fracture or wounds that was not cured for a long time * Coagulation dysfunction, hemorrhagic tendency or receiving anticoagulant therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | From randomization until the date of first documented progression or date of death from any cause, whichever came first. | PFS refers to the time interval between the randomization date and the initial record of PD or date of death, whichever is earlier. The presence of PD shall be determined in accordance with the result of the evaluation performed by the investigator, using with RECIST v1.1 criteria. The date of final tumor evaluation will be used as the censoring date for subjects who have not presented with disease progression or death by that date. The date of randomization will be used as the censoring date for subjects which have no death and post-baseline tumor evaluation. If a subject has no post-baseline tumor evaluation but recorded as dead, death will be count as PFS event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From randomization up to progressive disease or end of treatment (EOT) due to any cause. | The ORR is defined as the rate of complete response (CR) or partial response (PR) as the best overall response (BOR), based on evaluation of target lesions and non-target lesions with corroborant radiological method and determined by RECIST v1.1, for the ITT set of response evaluable subjects. Subjects who have no post-baseline tumor evaluation shall be regarded as subjects without ORR. Subjects who qualify for evaluation of CR or PR should have at least one available lesion for measurement with RECIST v1.1. |
| Disease Control Rate (DCR) | From randomization up to progressive disease or EOT due to any cause. | The DCR is defined as the rate of corroborant CR, PR and stable disease (SD) as the BOR, based on evaluation of target lesions and non-target lesions with corroborant radiological method and determined according to RECIST v1.1, for the ITT set of response evaluable subjects. |
| Over Survival (OS) | From randomization until death due to any cause. | The OS refers to the time interval between the randomization date and the date of death (any cause). The final known date of survival will be used as the censoring date for subjects that have not been reported to have died by the time of analysis. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Arm treatment arm- subjects will receive Fruquintinib 5mg orally, QD, plus BSC for 3 wks on/ 1 wk off. Patients will receive a cycles of 4 weeks of study treatment (1 cycle of study treatment includes 3 weeks of treatment and 1 week of drug discontinuation) or until the occurrence of progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or other conditions that meet the end of treatment criteria.
fruquintinib: fruquintinib is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off | 47 |
| Control Arm control arm- subjects will receive Fruquintinib placebo 5mg orally, QD, plus BSC for 3 wks on/ 1 wk off. Patients will receive a cycles of 4 weeks of study treatment (1 cycle of study treatment includes 3 weeks of treatment and 1 week of drug discontinuation) or until the occurrence of progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or other conditions that meet the end of treatment criteria.
placebo: Placebo is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off | 24 |
| Total | 71 |
Baseline characteristics
| Characteristic | Total | Control Arm | Treatment Arm |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 4 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 61 Participants | 20 Participants | 41 Participants |
| Race/Ethnicity, Customized ETHNICITY HAN | 71 Participants | 24 Participants | 47 Participants |
| Race/Ethnicity, Customized ETHNICITY NOT HAN | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 71 Participants | 24 Participants | 47 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 71 participants | 24 participants | 47 participants |
| Sex: Female, Male Female | 19 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Male | 52 Participants | 17 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 38 / 47 | 19 / 24 |
| other Total, other adverse events | 47 / 47 | 20 / 24 |
| serious Total, serious adverse events | 12 / 47 | 5 / 24 |
Outcome results
Primary
Progression Free Survival (PFS)
PFS refers to the time interval between the randomization date and the initial record of PD or date of death, whichever is earlier. The presence of PD shall be determined in accordance with the result of the evaluation performed by the investigator, using with RECIST v1.1 criteria. The date of final tumor evaluation will be used as the censoring date for subjects who have not presented with disease progression or death by that date. The date of randomization will be used as the censoring date for subjects which have no death and post-baseline tumor evaluation. If a subject has no post-baseline tumor evaluation but recorded as dead, death will be count as PFS event.
Time frame: From randomization until the date of first documented progression or date of death from any cause, whichever came first.
Population: The intention-to-treat set will contain all subjects in the Randomized set (RND) set subjects will be classified according to randomized treatment. The intent-to-treat principle is preserved. The Intention to Treat (ITT) will be used for analyses of PFS, OS, ORR and DCR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Arm | Progression Free Survival (PFS) | 4.731 months |
| Control Arm | Progression Free Survival (PFS) | 0.986 months |
Secondary
Disease Control Rate (DCR)
The DCR is defined as the rate of corroborant CR, PR and stable disease (SD) as the BOR, based on evaluation of target lesions and non-target lesions with corroborant radiological method and determined according to RECIST v1.1, for the ITT set of response evaluable subjects.
Time frame: From randomization up to progressive disease or EOT due to any cause.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Arm | Disease Control Rate (DCR) | 32 Participants |
| Control Arm | Disease Control Rate (DCR) | 5 Participants |
Secondary
Objective Response Rate (ORR)
The ORR is defined as the rate of complete response (CR) or partial response (PR) as the best overall response (BOR), based on evaluation of target lesions and non-target lesions with corroborant radiological method and determined by RECIST v1.1, for the ITT set of response evaluable subjects. Subjects who have no post-baseline tumor evaluation shall be regarded as subjects without ORR. Subjects who qualify for evaluation of CR or PR should have at least one available lesion for measurement with RECIST v1.1.
Time frame: From randomization up to progressive disease or end of treatment (EOT) due to any cause.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Arm | Objective Response Rate (ORR) | 1 Participants |
| Control Arm | Objective Response Rate (ORR) | 0 Participants |
Secondary
Over Survival (OS)
The OS refers to the time interval between the randomization date and the date of death (any cause). The final known date of survival will be used as the censoring date for subjects that have not been reported to have died by the time of analysis.
Time frame: From randomization until death due to any cause.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Arm | Over Survival (OS) | 7.721 months |
| Control Arm | Over Survival (OS) | 5.520 months |