Trial · NCT04322539
A Study of Efficacy and Safety of Fruquintinib (HMPL-013) in Participants With Metastatic Colorectal Cancer
NCT04322539, Phase 3, Completed, Hutchison Medipharma Limited; results first posted 2023-09-14
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. A Study of Efficacy and Safety of Fruquintinib (HMPL-013) in Participants With Metastatic Colorectal Cancer. Trials, record NCT04322539. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04322539
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- A Study of Efficacy and Safety of Fruquintinib (HMPL-013) in Participants With Metastatic Colorectal Cancer
- NCT number
- NCT04322539
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 691 participants, actual
- Lead sponsor
- Hutchison Medipharma Limited
- Conditions
- Metastatic Colorectal Cancer, Metastatic Colon Cancer
- Interventions
- Fruquintinib, Placebo
- First posted
- 2020-03-26
- Last updated
- 2025-04-04
- Results first posted
- 2023-09-14
Source ClinicalTrials.gov
Registered outcomes16
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Overall Survival (OS) | From date of randomization to death from any cause (up to 22 months) | OS was defined as the time (months) from date of randomization to death from any cause. OS was calculated as (date of death or last known alive - date of randomization + 1)/30.4375. Participants without report of death at the time of analysis will be censored at the date last known alive. |
| Secondary | Progression Free Survival (PFS), as Assessed by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 | From randomization until the first documentation of objective progression or death, whichever comes first (up to 22 months) | PFS was defined as the time (months) from randomization until the first radiographic documentation of objective progression as assessed by investigator using RECIST v1.1, or death from any cause, whichever comes first. More specifically, PFS was determined using all data until the last evaluable visit prior to or on the date of: (i) radiographic disease progression (PD) per RECIST v1.1; (ii) withdrawal of consent to obtain additional scans on study; or (iii) initiation of subsequent anticancer therapy other than the study drugs, whichever was earlier. PD was defined as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; and the appearance of one or more new lesions. |
| Secondary | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | From randomization until the first documentation of best overall response (up to 22 months) | ORR was defined as the percentage of participants who achieved a best overall response of confirmed complete response (CR) or partial response (PR), per RECIST v1.1, as determined by the investigator. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm). |
| Secondary | Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | From randomization until the first documentation of best overall response (up to 22 months) | DCR was defined as percentage of participants achieving a best overall response of confirmed CR, PR, or stable disease (SD) (for at least 7 weeks) per RECIST v1.1, as determined by the investigator. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum on study. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. |
| Secondary | Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | From first occurrence of PR or CR until the first documentation progression or death, whichever comes first (up to 22 months | DOR was defined as the time (in months) from the first occurrence of PR or CR by RECIST Version 1.1, until the first date that progressive disease is documented by RECIST Version 1.1, or death, whichever comes first. Only those participants with confirmed responses of CR or PR were included in this analysis. DOR was calculated as (date of death or PD or last assessment - date of first occurrence of confirmed CR or PR + 1)/30.4375. |
| Secondary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | From start of study drug administration up to approximately 40 months | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE was considered a TEAE if the onset date was on or after the start of study treatment or if the onset date was missing, or if the AE had an onset date before the start of study treatment but worsened in severity after the study treatment until 30 days after the last dose of study treatment or a new treatment of anti-tumor therapy, whichever was earlier. After this period, treatment-related SAEs were also considered as TEAEs. AEs with an unknown/not reported onset date were also included. |
| Secondary | Observed Plasma Concentrations of Fruquintinib and Metabolite M11 | Cycle 1 (Day 1 and 21): Pre-dose, 1, 2, 3 and 4 hours; Cycle 2 (Day 21): Predose and 2 hours, Cycle 3 (Day 1): Pre-dose, Cycle 3 (Day 21): Pre-dose and 2 hours, Cycle 5, 7, 9, 11, 13, 15 and 17 (Day 1): Pre-dose (Each cycle = 28 days) | Plasma samples were collected from the participants at the defined time points. Plasma concentrations were measured using a validated, specific, and sensitive liquid chromatography tandem mass spectrometry method. M11 is the active metabolite for the study drug. |
| Secondary | Change From Baseline of Electrocardiogram (ECG) Results - QTcF Intervals Using Fridericia's Formula | Baseline, Cycle 1 (Day 1 and 21): Pre-dose, 1, 2, 3 and 4 hours; Cycle 2 and 3 (Day 21): Pre-dose (Each cycle = 28 days) | QT Interval: Ventricular depolarization plus ventricular repolarization Normal Range: 400 to 460 milliseconds (msec). QTc: QT interval corrected based on the patient's heart rate. QTcF: An electrocardiographic finding in which the QT interval corrected for heart rate using Fridericia's formula. QTc = QT/∛(RR) RR = Respiration rate. |
| Secondary | Change From Baseline of ECG Results -QTcB Intervals Using Bazzett's Formula | Baseline, Cycle 1 (Day 1 and 21): Pre-dose, 1, 2, 3 and 4 hours; Cycle 2 and 3 (Day 21): Pre-dose (Each cycle = 28 days) | QT Interval: Ventricular depolarization plus ventricular repolarization Normal Range: 400 to 460 msec. QTc: QT interval corrected based on the patient's heart rate. QTcB: An electrocardiographic finding in which the QT interval corrected for heart rate using Bazzett's formula. |
| Secondary | Correlation Between Fruquintinib Exposure (CminSS) and Efficacy Parameters (OS) | Up to 22 months | Model-predicted steady-state minimum plasma concentrations (CminSS) of fruquintinib based on the starting dose or adjusted for relative dose intensity \[RDI\] were used as the exposure measures in the efficacy exposure-response analyses. The correlation between OS and exposure was estimated using multivariable Cox proportional hazards modeling. OS was analyzed as time-to-event variable using a survival model. The efficacy exposure-response analyses included participants with mCRC and pooled the data from the fruquintinib group of current Study 2019-013-GLOB1 (N=328) and from Cohort B of Study 2015-013-00US1 (NCT03251378) (N=40) as per planned analysis. Here, the "unit of measure" i.e., '1/(nanogram per milliliter \[ng/mL\])', corresponds to the coefficient that describes the relationship between the probability of survival and CminSS value. |
1 to 10 of 16Source ClinicalTrials.gov
See all 16 registered outcomesOutcomes16
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Overall Survival (OS) | From date of randomization to death from any cause (up to 22 months) | ITT population included all randomized participants. | months | MEDIAN |
| SECONDARY | Progression Free Survival (PFS), as Assessed by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 | From randomization until the first documentation of objective progression or death, whichever comes first (up to 22 months) | ITT population included all randomized participants. | months | MEDIAN |
| SECONDARY | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | From randomization until the first documentation of best overall response (up to 22 months) | ITT population included all randomized participants. | percentage of participants | NUMBER |
| SECONDARY | Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | From randomization until the first documentation of best overall response (up to 22 months) | ITT population included all randomized participants. | percentage of participants | NUMBER |
| SECONDARY | Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | From first occurrence of PR or CR until the first documentation progression or death, whichever comes first (up to 22 months | Analysis was performed on subset of participants who had a response. Here, '0' in 'overall number of participants analyzed represents that DOR could only be analyzed in participants who achieved a response. As no participant in the Placebo Plus BSC Group cohort achieved any response, no DOR is available. | months | MEDIAN |
| SECONDARY | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | From start of study drug administration up to approximately 40 months | SP included all randomized participants who received at least 1 dose of study drug. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Observed Plasma Concentrations of Fruquintinib and Metabolite M11 | Cycle 1 (Day 1 and 21): Pre-dose, 1, 2, 3 and 4 hours; Cycle 2 (Day 21): Predose and 2 hours, Cycle 3 (Day 1): Pre-dose, Cycle 3 (Day 21): Pre-dose and 2 hours, Cycle 5, 7, 9, 11, 13, 15 and 17 (Day 1): Pre-dose (Each cycle = 28 days) | PK population was used for tabulation of fruquintinib and M11 concentrations from PK plasma samples collected from the Fruquintinib + BSC Group. PK samples for the Placebo + BSC Group were not analyzed. Here, Overall Number of Participants Analyzed signifies those participants in the Fruquintinib + BSC Group who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable at the specified timepoints. | nanogram/milliliter (ng/mL) | MEAN |
| SECONDARY | Change From Baseline of Electrocardiogram (ECG) Results - QTcF Intervals Using Fridericia's Formula | Baseline, Cycle 1 (Day 1 and 21): Pre-dose, 1, 2, 3 and 4 hours; Cycle 2 and 3 (Day 21): Pre-dose (Each cycle = 28 days) | SP included all randomized participants who received at least 1 dose of study drug. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable at the specified time points. | millisecond (msec) | MEAN |
| SECONDARY | Change From Baseline of ECG Results -QTcB Intervals Using Bazzett's Formula | Baseline, Cycle 1 (Day 1 and 21): Pre-dose, 1, 2, 3 and 4 hours; Cycle 2 and 3 (Day 21): Pre-dose (Each cycle = 28 days) | SP included all randomized participants who received at least 1 dose of study drug. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure and Number analyzed signifies those participants who were evaluable at the specified timepoints. | msec | MEAN |
| SECONDARY | Correlation Between Fruquintinib Exposure (CminSS) and Efficacy Parameters (OS) | Up to 22 months | The efficacy exposure-response analyses included participants who were evaluable for the population PK analysis and therefore had PK parameter estimates to enable estimation of fruquintinib exposure and evaluated for the parameter/endpoint in question. Here, overall number of participants analyzed signified those participants who were evaluable for this outcome measure. The population for this measure included participants from both studies 2015-013-00US1 and the current study. | 1/(ng/mL) | NUMBER |
1 to 10 of 16Source ClinicalTrials.gov
See all 16 outcomesResults by group134
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Overall Survival (OS) | Fruquintinib + BSC Group | 7.4 | 95% Confidence Interval 6.7 to 8.2 | months | |
| Overall Survival (OS) | Placebo + BSC Group | 4.8 | 95% Confidence Interval 4.0 to 5.8 | months | |
| Progression Free Survival (PFS), as Assessed by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 | Fruquintinib + BSC Group | 3.7 | 95% Confidence Interval 3.5 to 3.8 | months | |
| Progression Free Survival (PFS), as Assessed by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 | Placebo + BSC Group | 1.8 | 95% Confidence Interval 1.8 to 1.9 | months | |
| Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | Fruquintinib + BSC Group | 1.5 | 95% Confidence Interval 0.6 to 3.1 | percentage of participants | |
| Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | Placebo + BSC Group | 0 | 95% Confidence Interval 0.0 to 1.6 | percentage of participants | |
| Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | Fruquintinib + BSC Group | 55.5 | 95% Confidence Interval 50.9 to 60.1 | percentage of participants | |
| Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | Placebo + BSC Group | 16.1 | 95% Confidence Interval 11.6 to 21.5 | percentage of participants | |
| Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | Fruquintinib + BSC Group | 10.7 | 95% Confidence Interval 3.9 to NA | months | |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Fruquintinib + BSC Group | Participants with TEAEs | 451 | Participants |
1 to 10 of 134Source ClinicalTrials.gov
See all 134 results by groupParticipant flow10
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Fruquintinib + Best Supportive Care (BSC) Group | 461 | |
| Overall Study | STARTED | Placebo + BSC Group | 230 | |
| Overall Study | Safety Population (SP) | Fruquintinib + Best Supportive Care (BSC) Group | 456 | |
| Overall Study | Safety Population (SP) | Placebo + BSC Group | 230 | |
| Overall Study | Pharmacokinetic (PK) Population | Fruquintinib + Best Supportive Care (BSC) Group | 329 | |
| Overall Study | Pharmacokinetic (PK) Population | Placebo + BSC Group | 2 | |
| Overall Study | COMPLETED | Fruquintinib + Best Supportive Care (BSC) Group | 0 | |
| Overall Study | COMPLETED | Placebo + BSC Group | 0 | |
| Overall Study | NOT COMPLETED | Fruquintinib + Best Supportive Care (BSC) Group | 461 | |
| Overall Study | NOT COMPLETED | Placebo + BSC Group | 230 |
Source ClinicalTrials.gov
Adverse events420
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Asthenia | General disorders | Fruquintinib + BSC Group | 153 | 456 | |
| other | Asthenia | General disorders | Placebo + BSC Group | 52 | 230 | |
| other | Fatigue | General disorders | Fruquintinib + BSC Group | 93 | 456 | |
| other | Fatigue | General disorders | Placebo + BSC Group | 37 | 230 | |
| other | Mucosal inflammation | General disorders | Fruquintinib + BSC Group | 62 | 456 | |
| other | Mucosal inflammation | General disorders | Placebo + BSC Group | 6 | 230 | |
| other | Pyrexia | General disorders | Fruquintinib + BSC Group | 43 | 456 | |
| other | Pyrexia | General disorders | Placebo + BSC Group | 22 | 230 | |
| other | Oedema peripheral | General disorders | Fruquintinib + BSC Group | 23 | 456 | |
| other | Oedema peripheral | General disorders | Placebo + BSC Group | 17 | 230 |
1 to 10 of 420Source ClinicalTrials.gov
See all 420 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Fruquintinib + BSC Group | 411 | 461 |
| Total, all-cause mortality | Placebo + BSC Group | 203 | 230 |
| Total, other adverse events | Fruquintinib + BSC Group | 446 | 456 |
| Total, other adverse events | Placebo + BSC Group | 205 | 230 |
| Total, serious adverse events | Fruquintinib + BSC Group | 173 | 456 |
| Total, serious adverse events | Placebo + BSC Group | 88 | 230 |
Source ClinicalTrials.gov
Papers6
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons3
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
| Comparison | Source |
|---|---|
| Fruquintinib + BSC Group vs Placebo + BSC Group: Health Care Resource Utilization: Number of Participants With Any Concomitant Medications Prescribed | Trial comparisons |
| Fruquintinib + BSC Group vs Placebo + BSC Group: deaths from any cause | Trial comparisons |
| Fruquintinib + BSC Group vs Placebo + BSC Group: serious adverse events | Trial comparisons |
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
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GET https://conductscience.org/api/trials/v1/NCT04322539/results?page=2