Advanced Solid TumorsPhase 1NCT03251378
A Multi-Center, Open-Label Study of Fruquintinib in Solid Tumors and Colorectal, and Breast Cancers
A Phase 1 study testing Fruquintinib (HMPL-013) in people with Advanced Solid Tumors and Metastatic Colon Cancer, run by Hutchison Medipharma Limited at 9 sites in United States.
Trial summary
An open-label, dose escalation and expansion clinical trial to evaluate the safety, tolerability, and PK of fruquintinib in patients with advanced solid tumors, metastatic colorectal cancer and metastatic breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors, Metastatic Colon Cancer, Metastatic Breast Cancer
- What is being tested?
- Fruquintinib (HMPL-013)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 129 participants
- Where
- 9 sitesUnited States
- Study dates
- 11 Dec 2017to 30 Mar 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Fully understand the study and voluntarily sign the ICF;
- ≥18years of age;
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
- Dose Escalation Phase:
- Histologically or cytologically documented, locally advanced or metastatic solid malignancy of any type (except squamous NSCLC) that has progressed on approved systemic therapy, and for whom no effective therapy or standard of care exists. This cohort is closed to enrollment.
- Dose Expansion Phase:
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- Cohort A: Histologically or cytologically documented, locally advanced or metastatic solid malignancy of any type (except squamous NSCLC), that has progressed on approved systemic therapy, and for whom no effective therapy or standard of care exists. This cohort is closed to enrollment.
- Cohort B: Histologically or cytologically documented mCRC in patients that have progressed on, or had intolerable toxicity with at least 1 FDA-approved third-line systemic therapy (trifluridine/tipiracil or regorafenib). Patients must also have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and an anti-EGFR therapy for patients who had RAS wild-type tumors. This cohort is currently enrolling.
- Cohort C: Histologically or cytologically documented adenocarcinoma of the colon or rectum. Patients must have progressed on, or had intolerable toxicity to, at least 2 prior regimens of standard chemotherapy, but must not have received prior TAS-102 or regorafenib. Prior therapy could have included adjuvant chemotherapy if a tumor had recurred within 6 months after the last administration of treatment. Patients must have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biological therapy and, if RAS wild-type, an anti-EGFR therapy
- Cohort D only: Histologically- or cytologically-confirmed Her2-negative, hormone receptor positive (ER+ and/or PR+) breast cancer
- Cohort E only: Histologically- or cytologically- confirmed triple negative breast cancer
Who cannot join
- Patients will be excluded from the study, if any of the following criteria is met:
- Severe anemia, neutropenia, thrombocytopenia
- Moderate to severe renal or hepatic impairment
- Uncontrolled hypertension
- Risk of, or active hemorrhage: history or presence of active gastric/duodenal ulcer or ulcerative colitis, active hemorrhage of an unresected gastrointestinal tumor, history of perforation of fistulas; or any other condition that could possibly result in gastrointestinal tract hemorrhage or perforation within 6 months prior to screening;
- History of a thromboembolic event (including deep vein thrombosis [DVT], pulmonary embolism, stroke and/or transient ischemic attack) within 6 months prior to screening;
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- Patients with squamous NSCLC;
- Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction or coronary artery bypass surgery within 6 months prior to enrollment, severe or unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, ventricular arrhythmias requiring treatment, or left ventricular ejection fraction (LVEF) <50%;
- Patients who have ever received a VEGFR inhibitor, except for patients with mCRC enrolled in the dose expansion phase;
- Systemic anti-neoplastic therapies or any investigational therapy within 4 weeks prior to the first dose of study drug, including chemotherapy, radical radiotherapy, hormonotherapy, biotherapy and immunotherapy;
- Systemic small molecule targeted therapies (e.g., tyrosine kinase inhibitors) within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of study drug;
- Palliative radiotherapy for bone metastasis/lesion within 2 weeks prior to the initiation of study drug;
- Brachytherapy (ie, implantation of radioactive seeds) within 60 days prior to the first dose of study drug;
- Known human immunodeficiency virus (HIV) infection;
- Known clinically significant history of liver disease, including cirrhosis, current alcohol abuse or active viral hepatitis. For patients with evidence of chronic hepatitis B (HBV), the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV who are currently on treatment, they are eligible if they have an undetectable HCV viral load;
- Tumor invasion of a large vascular structure, eg, pulmonary artery, superior or inferior vena cava.;
- Women who are pregnant or lactating;
- Brain metastases and/or spinal cord compression untreated with surgery and/or radiotherapy, and without clinical imaging evidence of stable disease for 14 days or longer; patients requiring steroids within 4 weeks prior to start of study treatment will be excluded;
- No other malignancy, except for non-melanoma skin cancer, during the 5 years prior to screening;
- Inability to take medication orally, dysphagia or an active gastric ulcer resulting from previous surgery (eg, gastric bypass) or a severe gastrointestinal disease, or any other condition that investigators believe may affect absorption of the investigational product;
- Other disease, metabolic disorder, physical examination anomaly, abnormal laboratory result, or any other condition that investigators suspect may prohibit use of the investigational product, affect interpretation of study results, or put the patient at undue risk of harm based on the investigator's assessment;
- Known hypersensitivity to fruquintinib or any of its excipients.
- For Cohort C only: patients who have been previously treated with TAS-102 or regorafenib
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
University of Colorado Cancer Center
Aurora, Colorado, 80045
MD Anderson Cancer Center
Houston, Texas, 77030
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, 37232
Mayo Clinic Arizona
Phoenix, Arizona, 85054
Hem-Onc Associates of the Treasure Coast
Port Saint Lucie, Florida, 34952
Mayo Clinic Rochester
Rochester, Minnesota, 55902
California Cancer Care Associates for Research & Excellence, Inc.
San Marcos, California, 92069
St. Joseph Heritage Healthcare
Santa Rosa, California, 95403
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Multi-Center, Open-Label, Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Anticancer Activity of Fruquintinib in Patients With Advanced Solid Tumors
An open-label, dose escalation and expansion clinical trial to evaluate the safety, tolerability, and PK of fruquintinib in patients with advanced solid tumors, metastatic colorectal cancer and metastatic breast cancer.
Read the detailed description
The study was an open-label, dose escalation and expansion clinical trial to evaluate the safety, tolerability, and PK of fruquintinib in patients with advanced solid tumors. The study consisted of two phases:
- A dose escalation phase - Two dose cohorts were evaluated including 3 mg orally QD 3 weeks on/1 week off and 5 mg orally QD 3 weeks on/1 week off. A 3+3 design was used for this portion of the study.
- A dose expansion phase - Five cohorts were evaluated in Dose Expansion phase. Cohort A evaluated the MTD/RP2D in patients with advanced solid tumors of any type. Cohort B and Cohort C evaluated the MTD/RP2D in metastatic colorectal cancer patients. Cohort D and Cohort E evaluated the MTD/RP2D in metastatic breast cancer patients.
Study was conducted at 9 sites in the United States.
- Conditions
- Advanced Solid Tumors, Metastatic Colon Cancer, Metastatic Breast Cancer, Triple Negative Breast Cancer, HER2-negative Breast Cancer, Hormone Receptor Positive Breast Carcinoma
- Being tested
- Fruquintinib (HMPL-013)
- Keywords
- VEGF, colorectal, breast
- Medical subject headings
- Colonic Neoplasms, Breast Neoplasms, Triple Negative Breast Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fruquintinib (HMPL-013)Drug
Also called HMPL-013
Fruquintinib is a small molecule tyrosine kinase inhibitor (TKI) that targets VEGFR-1, -2, and -3, with a novel chemical structure which belongs to the quinazoline class.
| Study group | Role | What they receive |
|---|---|---|
| 3 mg Dose Escalation | Experimental | 3 mg of Fruquintinib (HMPL-013), capsule taken orally, daily, 3 weeks on, 1 week off Receives: Drug: Fruquintinib (HMPL-013) |
| 5 mg Dose Escalation | Experimental | 5 mg of Fruquintinib (HMPL-013), capsule taken orally, daily, 3 weeks on, 1 week off Receives: Drug: Fruquintinib (HMPL-013) |
| Fruquintinib Expansion Cohort A | Experimental | 5 mg fruquintinib (HMPL-013) capsule taken orally, daily, 3 weeks on, 1 week off in patients with advanced solid tumors of any type. Receives: Drug: Fruquintinib (HMPL-013) |
| Metastatic Colorectal Cancer Expansion Cohort B (prior trifluridine/tipiracil or regorafenib) | Experimental | 5 mg fruquintinib (HMPL-013) capsule taken orally, daily, 3 weeks on, 1 week off in patients with metastatic colorectal cancer who have progressed on or had intolerable toxicity to TAS-102, regoragenib, or both. Receives: Drug: Fruquintinib (HMPL-013) |
| Metastatic Colorectal Cancer Expansion Cohort C (no prior trifluridine/tipiracil or regorafenib) | Experimental | 5 mg fruquintinib (HMPL-013) capsule taken orally, daily, 3 weeks on, 1 week off in patients with metastatic colorectal cancer who have not been treated with TAS-102 or regorafenib. Receives: Drug: Fruquintinib (HMPL-013) |
| Metastatic Breast Cancer (HR positive, HER2 negative) Expansion Cohort D | Experimental | 5 mg fruquintinib (HMPL-013) capsule taken orally, daily, 3 weeks on, 1 week off in patients with metastatic Her2-negative, hormone receptor positive breast cancer. Receives: Drug: Fruquintinib (HMPL-013) |
| Metastatic Breast Cancer (TNBC) Expansion Cohort E | Experimental | 5 mg fruquintinib (HMPL-013) capsule taken orally, daily, 3 weeks on, 1 week off in patients with metastatic triple negative (Her2-negative, ER-negative, PR-negative) breast cancer. Receives: Drug: Fruquintinib (HMPL-013) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Escalation Phase: Number of Participants With Dose-limiting Toxicities (DLTs)
Dose-limiting toxicity was defined as: Any Grade 4 non-hematologic toxicity; Any Grade 3 non-hematologic toxicity related to study drug except for nausea/vomiting, diarrhea, constipation, hypertension, and electrolyte imbalances downgraded within 3-days with appropriate supportive treatment; Grade 4 neutropenia lasting >3 days; Grade 3 febrile neutropenia (absolute neutrophil count [ANC] <1.0*10^9 per liter [/L] with a single temperature of greater than (>) 38.3 degree centigrade (°C) or a sustained temperature of greater than or equal to (>=) 38°C for more than 1 hour); Grade 4 thrombocytopenia or Grade 3 thrombocytopenia associated with bleeding; Dose interruption for >14 days due to toxicity.
Measured: Cycle 1 (cycle length equal to [=] 28 days)
Dose Escalation Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
TEAEs were defined as AEs that started or worsened in severity on or after the first dose of study medication and no later than 37 days after the date of last study treatment. A serious adverse event (SAE) was any AE that had any of the following characteristics: Fatal (that was, the AE actually caused or led to death, except for deaths caused by the progress of disease); Life threatening (that was, AE, in view of the investigator, places participant at immediate risk of death); Required or prolonged inpatient hospitalization (excluding emergency or outpatient treatment); Resulted in persistent or significant disability/incapacity (that was, the AE resulted in substantial disruption of the participant's ability to conduct normal life functions).
Measured: From first dose of study drug up to 37 days after last dose of study drug (i.e., up to 29 months)
Dose Expansion Phase: Progression Free Survival (PFS) Rate
PFS was defined as time from date of first dosing until date of an objective disease progression (PD) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 or death due to any cause, whichever comes first. PFS was determined using all data until last evaluable visit prior to or on date of: (i) radiographic PD per RECIST v1.1; (ii) withdrawal of consent to obtain additional scans on study; or (iii) initiation of subsequent anticancer therapy other than study drugs, whichever was earlier. PFS rate was defined as probability of being disease progression free at selected timepoints such as 16 weeks and was calculated using Brookmeyer-Crowley method based on PFS events observed up to 29 months. PD:at least 20 percent (%) increase in sum of diameters of target lesions, taking as reference smallest sum on study, including baseline; an absolute increase of at least 5 millimeter (mm) in sum of diameters of target lesions; and appearance of one or more new lesions.
Measured: From the first dose of study drug to disease progression, or death, whichever occurred first (i.e., up to 29 months)
Secondary outcomes (15)
Dose Escalation and Expansion Phase: Maximum Observed Plasma Concentration (Cmax) of Fruquintinib
Cmax of fruquintinib was reported.
Measured: Dose Escalation and Cohort A of Expansion Phases: Predose, 1, 2, 4, 8, 24 hours post-dose on Days 1, 14, and 21 of Cycle 1; Cohorts B, C, D, E of Expansion Phase: Predose, 1, 2, 4, 8, 24 hours post-dose on Days 1 and 14 of Cycle 1 (Cycle 1 length=28 days)
Dose Escalation and Expansion Phase: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Fruquintinib
Tmax of fruquintinib over a dosing intervals were reported.
Measured: Dose Escalation and Cohort A of Expansion Phases: Predose, 1, 2, 4, 8, 24 hours post-dose on Days 1, 14, and 21 of Cycle 1; Cohorts B, C, D, E of Expansion Phase: Predose, 1, 2, 4, 8, 24 hours post-dose on Days 1 and 14 of Cycle 1 (Cycle 1 length=28 days)
Dose Escalation and Expansion Phase: Minimum Observed Plasma Concentration (Cmin) of Fruquintinib
Cmin of fruquintinib was reported.
Measured: Dose Escalation and Cohort A of Expansion Phases: Predose, 1, 2, 4, 8, 24 hours post-dose on Days 14, and 21 of Cycle 1; Cohorts B, C, D, E of Expansion Phase: Predose, 1, 2, 4, 8, 24 hours post-dose on Day 14 of Cycle 1 (Cycle 1 length=28 days)
Dose Escalation and Expansion Phase: Time to Reach Minimum Observed Plasma Concentration (Tmin) of Fruquintinib
Tmin of fruquintinib was reported.
Measured: Dose Escalation and Cohort A of Expansion Phases: Predose, 1, 2, 4, 8, 24 hours post-dose on Days 14, and 21 of Cycle 1; Cohorts B, C, D, E of Expansion Phase: Predose, 1, 2, 4, 8, 24 hours post-dose on Day 14 of Cycle 1 (Cycle 1 length=28 days)
Dose Escalation and Expansion Phase: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) of Fruquintinib
AUC0-24 of fruquintinib was reported.
Measured: Dose Escalation and Cohort A of Expansion Phases: Predose, 1, 2, 4, 8, 24 hours post-dose on Days 1, 14, and 21 of Cycle 1; Cohorts B, C, D, E of Expansion Phase: Predose, 1, 2, 4, 8, 24 hours post-dose on Days 1 and 14 of Cycle 1 (Cycle 1 length=28 days)
Dose Escalation and Expansion Phase: Apparent Clearance at Steady State (CL/Fss) of Fruquintinib
CL/Fss was calculated as Dose/AUC0-t. As planned, CL/Fss was assessed at Cycle 1 Days 14 and 21 after multiple dose administration in Dose Escalation Phase and Cohort A of Dose Expansion Phase; and at Cycle 1 Day 14 for Cohort B, C, D, E of Expansion Phase.
Measured: Dose Escalation and Cohort A of Expansion Phases: Predose, 1, 2, 4, 8, 24 hours post-dose on Days 14, and 21 of Cycle 1; Cohorts B, C, D, E of Expansion Phase: Predose, 1, 2, 4, 8, 24 hours post-dose on Day 14 of Cycle 1 (Cycle 1 length=28 days)
Dose Escalation and Expansion Phase: Accumulation Ratio Based on Cmax of Fruquintinib
Accumulation ratio based on Cmax for Cycle 1 Day 14 was calculated as Day 14 Cmax /Day 1 Cmax and for Cycle 1 Day 21 was calculated as Day 21 Cmax /Day 1 Cmax. Accumulation ratio based on Cmax of fruquintinib was reported.
Measured: Dose Escalation and Cohort A of Expansion Phases: Predose, 1, 2, 4, 8, 24 hours post-dose on Days 14 and 21 of Cycle 1; Cohorts B, C, D, E of Expansion Phase: Predose, 1, 2, 4, 8, 24 hours post-dose on Day 14 of Cycle 1 (Cycle 1 length=28 days)
Dose Escalation and Expansion Phase: Accumulation Ratio Based on AUC0-24 Hours of Fruquintinib
Accumulation ratio for Cycle 1 Day 14 was calculated as AUC0-24 at Day 14 divided by AUC0-24h at Day 1, and for Cycle 1 Day 21 was calculated as AUC0-24 at Day 21 divided by AUC0-24 at Day 1. Accumulation ratio based on AUC0-24 of fruquintinib was reported.
Measured: Dose Escalation and Cohort A of Expansion Phases: Predose, 1, 2, 4, 8, 24 hours post-dose on Days 14 and 21 of Cycle 1; Cohorts B, C, D, E of Expansion Phase: Predose, 1, 2, 4, 8, 24 hours post-dose on Day 14 of Cycle 1 (Cycle 1 length=28 days)
Dose Escalation and Expansion Phase: Objective Response Rate (ORR)
ORR was defined as the percentage of participants with objective complete response (CR) or partial response (PR) response per RECIST version 1.1. As per RECIST 1.1; CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Measured: From the first dose of study drug until first documentation of best overall response (i.e., up to 29 months)
Dose Escalation and Expansion Phase: Disease Control Rate (DCR)
DCR was defined as the percentage of participants with a best overall response (BOR) of confirmed CR, confirmed PR or stable disease (SD) (for 7 weeks) per RECIST version 1.1. As per RECIST 1.1; CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study [this might include the baseline sum]).
Measured: From the first dose of study drug until first documentation of best overall response (i.e., up to 29 months)
Dose Escalation and Expansion Phase: Duration of Response (DoR)
DoR was defined as the time (in months) from the date of the first objective response (CR or PR) until the date of the documented progression or of death, whichever comes first. DoR was only analyzed for participants whose best overall response (BOR) was either CR or PR. As per RECIST 1.1; CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. 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 (this might include the baseline sum). DoR was calculated using the Kaplan-Meier method.
Measured: From the date of the first objective response (CR or PR) until the date of the documented disease progression or of death, whichever comes first (i.e., up to 29 months)
Dose Escalation and Expansion Phase: Progression Free Survival (PFS)
PFS was defined as the time (in months) from date of first dosing until the date of an objective disease progression as per RECIST version 1.1 or death due to any cause, whichever comes first. PFS was determined using all the assessment data up until the last evaluable visit prior to or on the date of (i) disease progression as defined by RECIST version 1.1 or death; or (ii) withdrawal of consent; or (iii) receiving subsequent anti-cancer therapy, whichever is earlier. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this might include the baseline sum). PFS was calculated using the Kaplan-Meier method.
Measured: From date of first dose until the date of an objective disease progression or death due to any cause, whichever comes first (i.e., up to 29 months)
Dose Escalation and Expansion Phase: Overall Survival (OS)
OS was defined as the time interval (in months) between the first dose date and the date of death (any cause). OS was calculated using the Kaplan-Meier method.
Measured: From first dose date to the date of death (due to any cause) (i.e., up to 29 months)
Dose Escalation and Expansion Phase: Percent Change From Baseline (PCFB) in Tumor Size
Tumor size was estimated using data on sum of diameters of target lesion. Percentage change in tumor size from baseline was determined for participants with measurable disease at baseline and derived by the percentage change in the sum of the diameters of target lesions (TLs) compared to baseline. Baseline was defined as the last evaluable tumor assessment result obtained prior to the first administration of study medication.
Measured: Baseline up to 29 months
Dose Expansion Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
TEAEs were defined as AEs that started or worsened in severity on or after the first dose of study medication and no later than 37 days after the date of last study treatment. A SAE was any AE that had any of the following characteristics: Fatal (that was, the AE actually caused or led to death, except for deaths caused by the progress of disease); Life threatening (that was, AE, in view of the investigator, places participant at immediate risk of death); Required or prolonged inpatient hospitalization (excluding emergency or outpatient treatment); Resulted in persistent or significant disability/incapacity (that was, the AE resulted in substantial disruption of the participant's ability to conduct normal life functions).
Measured: From first dose of study drug up to 37 days after last dose of study drug (i.e., up to 29 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2017
- Study start11 Dec 2017
- Primary completion13 Dec 2022
- Study completion30 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 129 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hutchison Medipharma Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- William Schelman, Study director, HUTCHMED International
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03251378
- Sponsor's protocol ID
- 2015-013-00US1
- Status last verified
- May 2024
- First submitted
- 19 Jul 2017
- Last updated
- 25 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wang-Gillam A, Schelman W, Ukrainskyj S, Chien C, Gonzalez M, Yang Z, Kania M, Yeckes-Rodin H. Phase 1/1b open-label, dose-escalation study of fruquintinib in patients with advanced solid tumors in the United States. Invest New Drugs. 2023 Dec;41(6):851-860. doi: 10.1007/s10637-023-01395-y. Epub 2023 Oct 5.
PubMed 37796398
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center, Open-Label, Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Anticancer Activity of Fruquintinib in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT03251378
- Acronym / sponsor ID
- 2015-013-00US1
- Conditions
- Advanced Solid Tumors, Metastatic Colon Cancer, Metastatic Breast Cancer, Triple Negative Breast Cancer, HER2-negative Breast Cancer, Hormone Receptor Positive Breast Carcinoma
- Keywords
- VEGF, colorectal, breast
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 129 participants (actual)
- Lead sponsor
- Hutchison Medipharma LimitedIndustry (pharma, biotech, devices)
- Study start
- 11 Dec 2017 (actual)
- Primary completion
- 13 Dec 2022 (actual)
- Study completion
- 30 Mar 2023 (actual)
- First posted
- 16 Aug 2017 (actual)
- Results
- Posted 25 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An open-label, dose escalation and expansion clinical trial to evaluate the safety, tolerability, and PK of fruquintinib in patients with advanced solid tumors, metastatic colorectal cancer and metastatic breast cancer.
Detailed description
The study was an open-label, dose escalation and expansion clinical trial to evaluate the safety, tolerability, and PK of fruquintinib in patients with advanced solid tumors. The study consisted of two phases:
- A dose escalation phase - Two dose cohorts were evaluated including 3 mg orally QD 3 weeks on/1 week off and 5 mg orally QD 3 weeks on/1 week off. A 3+3 design was used for this portion of the study.
- A dose expansion phase - Five cohorts were evaluated in Dose Expansion phase. Cohort A evaluated the MTD/RP2D in patients with advanced solid tumors of any type. Cohort B and Cohort C evaluated the MTD/RP2D in metastatic colorectal cancer patients. Cohort D and Cohort E evaluated the MTD/RP2D in metastatic breast cancer patients.
Study was conducted at 9 sites in the United States.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| 3 mg Dose Escalation | Experimental | Drug: Fruquintinib (HMPL-013)3 mg of Fruquintinib (HMPL-013), capsule taken orally, daily, 3 weeks on, 1 week off |
| 5 mg Dose Escalation | Experimental | Drug: Fruquintinib (HMPL-013)5 mg of Fruquintinib (HMPL-013), capsule taken orally, daily, 3 weeks on, 1 week off |
| Fruquintinib Expansion Cohort A | Experimental | Drug: Fruquintinib (HMPL-013)5 mg fruquintinib (HMPL-013) capsule taken orally, daily, 3 weeks on, 1 week off in patients with advanced solid tumors of any type. |
| Metastatic Colorectal Cancer Expansion Cohort B (prior trifluridine/tipiracil or regorafenib) | Experimental | Drug: Fruquintinib (HMPL-013)5 mg fruquintinib (HMPL-013) capsule taken orally, daily, 3 weeks on, 1 week off in patients with metastatic colorectal cancer who have progressed on or had intolerable toxicity to TAS-102, regoragenib, or both. |
| Metastatic Colorectal Cancer Expansion Cohort C (no prior trifluridine/tipiracil or regorafenib) | Experimental | Drug: Fruquintinib (HMPL-013)5 mg fruquintinib (HMPL-013) capsule taken orally, daily, 3 weeks on, 1 week off in patients with metastatic colorectal cancer who have not been treated with TAS-102 or regorafenib. |
| Metastatic Breast Cancer (HR positive, HER2 negative) Expansion Cohort D | Experimental | Drug: Fruquintinib (HMPL-013)5 mg fruquintinib (HMPL-013) capsule taken orally, daily, 3 weeks on, 1 week off in patients with metastatic Her2-negative, hormone receptor positive breast cancer. |
| Metastatic Breast Cancer (TNBC) Expansion Cohort E | Experimental | Drug: Fruquintinib (HMPL-013)5 mg fruquintinib (HMPL-013) capsule taken orally, daily, 3 weeks on, 1 week off in patients with metastatic triple negative (Her2-negative, ER-negative, PR-negative) breast cancer. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Fully understand the study and voluntarily sign the ICF;
- ≥18years of age;
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
- Histologically or cytologically documented, locally advanced or metastatic solid malignancy of any type (except squamous NSCLC) that has progressed on approved systemic therapy, and for whom no effective therapy or standard of care exists. This cohort is closed to enrollment.
- Cohort A: Histologically or cytologically documented, locally advanced or metastatic solid malignancy of any type (except squamous NSCLC), that has progressed on approved systemic therapy, and for whom no effective therapy or standard of care exists. This cohort is closed to enrollment.
Key exclusion criteria (23 listed)
- Severe anemia, neutropenia, thrombocytopenia
- Moderate to severe renal or hepatic impairment
- Uncontrolled hypertension
- Risk of, or active hemorrhage: history or presence of active gastric/duodenal ulcer or ulcerative colitis, active hemorrhage of an unresected gastrointestinal tumor, history of perforation of fistulas; or any other condition that could possibly result in gastrointestinal tract hemorrhage or perforation within 6 months prior to screening;
- History of a thromboembolic event (including deep vein thrombosis [DVT], pulmonary embolism, stroke and/or transient ischemic attack) within 6 months prior to screening;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fruquintinib (HMPL-013)Also: HMPL-013Fruquintinib is a small molecule tyrosine kinase inhibitor (TKI) that targets VEGFR-1, -2, and -3, with a novel chemical structure which belongs to the quinazoline class. | Drug | 3 mg Dose Escalation, 5 mg Dose Escalation, Fruquintinib Expansion Cohort A, Metastatic Breast Cancer (HR positive, HER2 negative) Expansion Cohort D, Metastatic Breast Cancer (TNBC) Expansion Cohort E, Metastatic Colorectal Cancer Expansion Cohort B (prior trifluridine/tipiracil or regorafenib), Metastatic Colorectal Cancer Expansion Cohort C (no prior trifluridine/tipiracil or regorafenib) |
Primary outcome
Dose Escalation Phase: Number of Participants With Dose-limiting Toxicities (DLTs)
Time frame: Cycle 1 (cycle length equal to [=] 28 days)
Dose-limiting toxicity was defined as: Any Grade 4 non-hematologic toxicity; Any Grade 3 non-hematologic toxicity related to study drug except for nausea/vomiting, diarrhea, constipation, hypertension, and electrolyte imbalances downgraded within 3-days with appropriate supportive treatment; Grade 4 neutropenia lasting >3 days; Grade 3 febrile neutropenia (absolute neutrophil count [ANC] <1.0*10^9 per liter [/L] with a single temperature of greater than (>) 38.3 degree centigrade (°C) or a sustained temperature of greater than or equal to (>=) 38°C for more than 1 hour); Grade 4 thrombocytopenia or Grade 3 thrombocytopenia associated with bleeding; Dose interruption for >14 days due to toxicity.
Dose Escalation Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Time frame: From first dose of study drug up to 37 days after last dose of study drug (i.e., up to 29 months)
TEAEs were defined as AEs that started or worsened in severity on or after the first dose of study medication and no later than 37 days after the date of last study treatment. A serious adverse event (SAE) was any AE that had any of the following characteristics: Fatal (that was, the AE actually caused or led to death, except for deaths caused by the progress of disease); Life threatening (that was, AE, in view of the investigator, places participant at immediate risk of death); Required or prolonged inpatient hospitalization (excluding emergency or outpatient treatment); Resulted in persistent or significant disability/incapacity (that was, the AE resulted in substantial disruption of the participant's ability to conduct normal life functions).
Dose Expansion Phase: Progression Free Survival (PFS) Rate
Time frame: From the first dose of study drug to disease progression, or death, whichever occurred first (i.e., up to 29 months)
PFS was defined as time from date of first dosing until date of an objective disease progression (PD) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 or death due to any cause, whichever comes first. PFS was determined using all data until last evaluable visit prior to or on date of: (i) radiographic PD per RECIST v1.1; (ii) withdrawal of consent to obtain additional scans on study; or (iii) initiation of subsequent anticancer therapy other than study drugs, whichever was earlier. PFS rate was defined as probability of being disease progression free at selected timepoints such as 16 weeks and was calculated using Brookmeyer-Crowley method based on PFS events observed up to 29 months. PD:at least 20 percent (%) increase in sum of diameters of target lesions, taking as reference smallest sum on study, including baseline; an absolute increase of at least 5 millimeter (mm) in sum of diameters of target lesions; and appearance of one or more new lesions.
15 secondary outcomes
Dose Escalation and Expansion Phase: Maximum Observed Plasma Concentration (Cmax) of Fruquintinib
Time frame: Dose Escalation and Cohort A of Expansion Phases: Predose, 1, 2, 4, 8, 24 hours post-dose on Days 1, 14, and 21 of Cycle 1; Cohorts B, C, D, E of Expansion Phase: Predose, 1, 2, 4, 8, 24 hours post-dose on Days 1 and 14 of Cycle 1 (Cycle 1 length=28 days)
Dose Escalation and Expansion Phase: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Fruquintinib
Time frame: Dose Escalation and Cohort A of Expansion Phases: Predose, 1, 2, 4, 8, 24 hours post-dose on Days 1, 14, and 21 of Cycle 1; Cohorts B, C, D, E of Expansion Phase: Predose, 1, 2, 4, 8, 24 hours post-dose on Days 1 and 14 of Cycle 1 (Cycle 1 length=28 days)
Dose Escalation and Expansion Phase: Minimum Observed Plasma Concentration (Cmin) of Fruquintinib
Time frame: Dose Escalation and Cohort A of Expansion Phases: Predose, 1, 2, 4, 8, 24 hours post-dose on Days 14, and 21 of Cycle 1; Cohorts B, C, D, E of Expansion Phase: Predose, 1, 2, 4, 8, 24 hours post-dose on Day 14 of Cycle 1 (Cycle 1 length=28 days)
Dose Escalation and Expansion Phase: Time to Reach Minimum Observed Plasma Concentration (Tmin) of Fruquintinib
Time frame: Dose Escalation and Cohort A of Expansion Phases: Predose, 1, 2, 4, 8, 24 hours post-dose on Days 14, and 21 of Cycle 1; Cohorts B, C, D, E of Expansion Phase: Predose, 1, 2, 4, 8, 24 hours post-dose on Day 14 of Cycle 1 (Cycle 1 length=28 days)
Dose Escalation and Expansion Phase: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) of Fruquintinib
Time frame: Dose Escalation and Cohort A of Expansion Phases: Predose, 1, 2, 4, 8, 24 hours post-dose on Days 1, 14, and 21 of Cycle 1; Cohorts B, C, D, E of Expansion Phase: Predose, 1, 2, 4, 8, 24 hours post-dose on Days 1 and 14 of Cycle 1 (Cycle 1 length=28 days)
Dose Escalation and Expansion Phase: Apparent Clearance at Steady State (CL/Fss) of Fruquintinib
Time frame: Dose Escalation and Cohort A of Expansion Phases: Predose, 1, 2, 4, 8, 24 hours post-dose on Days 14, and 21 of Cycle 1; Cohorts B, C, D, E of Expansion Phase: Predose, 1, 2, 4, 8, 24 hours post-dose on Day 14 of Cycle 1 (Cycle 1 length=28 days)
Dose Escalation and Expansion Phase: Accumulation Ratio Based on Cmax of Fruquintinib
Time frame: Dose Escalation and Cohort A of Expansion Phases: Predose, 1, 2, 4, 8, 24 hours post-dose on Days 14 and 21 of Cycle 1; Cohorts B, C, D, E of Expansion Phase: Predose, 1, 2, 4, 8, 24 hours post-dose on Day 14 of Cycle 1 (Cycle 1 length=28 days)
Dose Escalation and Expansion Phase: Accumulation Ratio Based on AUC0-24 Hours of Fruquintinib
Time frame: Dose Escalation and Cohort A of Expansion Phases: Predose, 1, 2, 4, 8, 24 hours post-dose on Days 14 and 21 of Cycle 1; Cohorts B, C, D, E of Expansion Phase: Predose, 1, 2, 4, 8, 24 hours post-dose on Day 14 of Cycle 1 (Cycle 1 length=28 days)
Dose Escalation and Expansion Phase: Objective Response Rate (ORR)
Time frame: From the first dose of study drug until first documentation of best overall response (i.e., up to 29 months)
Dose Escalation and Expansion Phase: Disease Control Rate (DCR)
Time frame: From the first dose of study drug until first documentation of best overall response (i.e., up to 29 months)
Dose Escalation and Expansion Phase: Duration of Response (DoR)
Time frame: From the date of the first objective response (CR or PR) until the date of the documented disease progression or of death, whichever comes first (i.e., up to 29 months)
Dose Escalation and Expansion Phase: Progression Free Survival (PFS)
Time frame: From date of first dose until the date of an objective disease progression or death due to any cause, whichever comes first (i.e., up to 29 months)
Dose Escalation and Expansion Phase: Overall Survival (OS)
Time frame: From first dose date to the date of death (due to any cause) (i.e., up to 29 months)
Dose Escalation and Expansion Phase: Percent Change From Baseline (PCFB) in Tumor Size
Time frame: Baseline up to 29 months
Dose Expansion Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Time frame: From first dose of study drug up to 37 days after last dose of study drug (i.e., up to 29 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37796398Wang-Gillam A, Schelman W, Ukrainskyj S, Chien C, Gonzalez M, Yang Z, Kania M, Yeckes-Rodin H. Phase 1/1b open-label, dose-escalation study of fruquintinib in patients with advanced solid tumors in the United States. Invest New Drugs. 2023 Dec;41(6):851-860. doi: 10.1007/s10637-023-01395-y. Epub 2023 Oct 5.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William Schelman study director
HUTCHMED International
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fruquintinib (HMPL-013) in people with Advanced Solid Tumors and Metastatic Colon Cancer, run by Hutchison Medipharma Limited at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Escalation Phase: Number of Participants With Dose-limiting Toxicities (DLTs) (time frame: Cycle 1 (cycle length equal to [=] 28 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03251378, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2024.