- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05003622
Phase 1 Safety Study of Encorafenib in Chinese Patients With Advanced Metastatic BRAF V600E Mutant Solid Tumors (OCEANI)
June 9, 2022 updated by: Pierre Fabre Medicament
Multicenter, Open-label, Phase 1 Study Investigating the Safety and Tolerability of Encorafenib Monotherapy in BRAF V600E-mutated Chinese Patients With Advanced Metastatic Solid Tumors
This is a phase 1, multicenter, open-label, single-arm study to investigate the safety and tolerability of encorafenib 300 mg once daily (QD) monotherapy in adult Chinese participants with B-RAF Proto-oncogene, Serine/threonine Kinase V600E (BRAF V600E) mutant advanced solid tumors (unresectable metastatic melanoma or metastatic non-small cell lung cancer (NSCLC)), who are BRAF-inhibitor treatment-naïve and have failed the previous therapy(ies) in the metastatic setting or are not eligible to standard therapy.
Participants will be eligible for the study based on identification of a BRAF V600E mutation in tumor tissue by a local National Medical Products Administration (NMPA) approved assay obtained prior to screening.
Study Overview
Status
Completed
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
3
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Guangdong
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Guangzhou, Guangdong, China, 510060
- Sun Yat-sen University Cancer Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Provide a signed and dated informed consent form (ICF).
- Chinese male or female with age ≥18 years old at the time of the informed consent.
- Documented histology- and/or cytology-confirmed metastatic melanoma or non-small cell lung cancer (NSCLC) (i.e. adenocarcinoma, large cell carcinoma, squamous cell carcinoma).
- Presence of B-RAF Proto-oncogene, Serine/threonine Kinase V600E Mutant (BRAF V600E) mutation as determined by a local laboratory with a National Medical Products Administration (NMPA) approved BRAF test.
- BRAF inhibitor treatment-naïve participants and having failed the previous therapy(ies) for metastatic disease or are not eligible to standard therapy.
- At least one tumor lesion as per investigator assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, which has neither been irradiated nor biopsied during the screening period. The irradiated lesion is acceptable only if it is proven as disease progression deemed measurable prior to study.
- Life expectancy ≥3 months.
- Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1.
- Adequate hematologic function at screening and baseline
- Adequate hepatic function at screening and baseline
- Adequate renal function at screening and baseline
- Able to comply with the study protocol as per investigator assessment including oral drug intake, complying scheduled visits, treatment plan, laboratory tests and other study procedures.
- Women are either postmenopausal for at least 1 year, or are surgically sterile for at least 6 weeks, or women of childbearing potential (WOCBP) must agree to take appropriate precautions to avoid pregnancy.
- Men must agree not to father child until 90 days after the last dose of study treatment.
Exclusion Criteria:
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to encorafenib, or its excipients.
- For metastatic NSCLC: documented anaplastic lymphoma kinase (ALK) fusion oncogene, ROS1 (c-ros oncogene 1) rearrangement or epidermal growth factor receptor (EGFR) sensitizing or driver mutation.
- Receipt of anticancer medications or investigational drugs within intervals before the first administration of study treatment.
- Symptomatic brain metastasis.
- Leptomeningeal disease.
- Participant has not recovered to ≤Grade 1 from toxic effects of prior therapy and/or complications from prior surgical treatment before starting study treatment.
- Current use of prohibited medication ≤1 week prior to start of the study treatment and/or concomitantly.
- Impairment of gastrointestinal function or disease which may significantly alter the absorption of oral study treatment.
- Impaired cardiovascular function or clinically significant cardiovascular diseases.
- Participants with active Hepatitis B virus (HBV) or Hepatitis C virus (HCV) or any other severe viral active infection (e.g. severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection).
- Evidence of active, non-infectious pneumonitis, history of interstitial lung disease that required oral or intravenous glucocorticoid steroids for management.
- Known history of a positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). Testing for HIV must be performed at sites where mandated locally.
- Participants who have had major surgery (e.g. inpatient procedure with regional or general anesthesia) within 6 weeks prior to start of study treatment.
Previous or concurrent malignancy within 2 years of study entry.
Except:
- Bowen's disease.
- Cured basal cell or squamous cell skin cancer.
- Gleason 6 prostate cancer.
- Treated in-situ carcinoma of cervix.
- Participant's conditions that contraindicates the use of study treatment and may affect interpretation of results or that may render the participant at high risk from treatment complications.
- Pregnant (confirmed by positive serum beta-human Chorionic Gonadotropin (ß-HCG) test), lactating or breast-feeding women.
- Is a family member of the Investigator or any associate, colleague, and employee assisting in the conduct of the study (secretary, nurse, technician).
- Is in a position likely to represent a conflict of interest.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: encorafenib
Encorafenib hard capsule will be orally self-administered.
A fixed-flat dose of 300 mg (4 x 75 mg) Per Oral (PO) encorafenib will be administered once-daily (QD).
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oral capsule
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Incidence of dose limiting toxicities (DLTs) experienced during Cycle 1
Time Frame: At the end of Cycle 1. Each cycle is 28 days.
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At the end of Cycle 1. Each cycle is 28 days.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence, nature and severity of treatment emergent adverse events (TEAEs)
Time Frame: Cycle 1 Day 1 through safety follow-up visit (30 days after end of treatment (EOT) visit or 7 days after end EOT visit/last dose if EOT not performed), approximately up to 6 months. Each cycle is 28 days.
|
Incidence, nature and severity of treatment emergent adverse events (TEAEs) graded as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03, TEAEs leading to dose interruption, reduction and discontinuation, treatment-emergent serious adverse events (SAEs) and deaths will be reported.
|
Cycle 1 Day 1 through safety follow-up visit (30 days after end of treatment (EOT) visit or 7 days after end EOT visit/last dose if EOT not performed), approximately up to 6 months. Each cycle is 28 days.
|
Incidence of treatment emergent adverse events (TEAEs) related to notable change from baseline of blood hematology parameters
Time Frame: Screening (Days -28 to -1), Cycle 1 Day 1 (if not done within 72 hours before the first dose), Cycle 1 Day 15, on Day 1 each subsequent cycle, end of treatment visit 30 day safety follow up visit, approximately up to 6 months. Each cycle is 28 days.
|
Clinically notable shift from baseline in blood hematology parameters data [Hemoglobin (Low/High); Leukocytes (Low/ High); Neutrophils (Low); Platelets (Low/High); Lymphocytes (Low/High)] will be graded using NCI CTCAE Version 4.03.
Clinically notable shift is defined as a worsening from baseline by at least 2 grades, or to grade 3 or above.
Number of participants with at least one clinically notable shift during study will be reported.
|
Screening (Days -28 to -1), Cycle 1 Day 1 (if not done within 72 hours before the first dose), Cycle 1 Day 15, on Day 1 each subsequent cycle, end of treatment visit 30 day safety follow up visit, approximately up to 6 months. Each cycle is 28 days.
|
Incidence of treatment emergent adverse events (TEAEs) related to notable change from baseline of blood clinical chemistry parameters
Time Frame: Screening (Days -28 to -1), Cycle 1 Day 1 (if not done within 72 hours before the first dose), Cycle 1 Day 15, on Day 1 each subsequent cycle, end of treatment visit 30 day safety follow up visit, approximately up to 6 months. Each cycle is 28 days.
|
Clinically notable shift from baseline in blood clinical chemistry parameter values [Phosphate (Low); Alanine Aminotransferase (High); Albumin (Low); Alkaline Phosphatase (High); Aspartate Aminotransferase (High); Bilirubin (High); Calcium Corrected (Low/High); Creatinine (High); Glucose (Low/High); Magnesium (Low/High); Potassium (Low/High); Sodium (Low/High)] will be graded using NCI-CTCAE, Version 4.03.
Clinically notable shift is defined as a worsening from baseline by at least 2 grades, or to grade 3 or above.
Number of participants with at least one clinically notable shift during study will be reported.
|
Screening (Days -28 to -1), Cycle 1 Day 1 (if not done within 72 hours before the first dose), Cycle 1 Day 15, on Day 1 each subsequent cycle, end of treatment visit 30 day safety follow up visit, approximately up to 6 months. Each cycle is 28 days.
|
Incidence of treatment emergent adverse events (TEAEs) related to notable change from baseline of coagulation parameters
Time Frame: Screening (Days -28 to -1), Cycle 1 Day 1 (if not done within 72 hours before the first dose), Cycle 1 Day 15, on Day 1 each subsequent cycle, end of treatment visit 30 day safety follow up visit, approximately up to 6 months. Each cycle is 28 days.
|
Clinically notable shift from baseline in coagulation parameters parameter values [activated partial thromboplastin time (seconds), international normalized ratio (INR) or prothrombin time (seconds)] will be graded using NCI-CTCAE, Version 4.03.
Number of participants with abnormal levels or notable shift during study will be reported.
|
Screening (Days -28 to -1), Cycle 1 Day 1 (if not done within 72 hours before the first dose), Cycle 1 Day 15, on Day 1 each subsequent cycle, end of treatment visit 30 day safety follow up visit, approximately up to 6 months. Each cycle is 28 days.
|
Incidence of treatment emergent adverse events (TEAEs) related to notable change from baseline of dipstick urinalysis
Time Frame: Days -28 to -1,Cycle1 Day1 (if not done w/in 72 hours before first dose),Cycle1 Day15,on Day1 each subsequent cycle,end of treatment visit 30 day safety FU visit,approx. up to 6 months. Add'l urinalysis in Cycle 1 Days 8 and 22. Each cycle is 28 days.
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Quantitative assessment of appearance, color, specific gravity, blood, glucose, leukocytes, ketones, pH and protein at each visit and changes from baseline (for quantitative parameters) will be calculated and tabulated.
Microscopy findings (normal/abnormal and clinical significance) will be recorded.
Number of participants with abnormal/ clinical significant changes during study will be reported.
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Days -28 to -1,Cycle1 Day1 (if not done w/in 72 hours before first dose),Cycle1 Day15,on Day1 each subsequent cycle,end of treatment visit 30 day safety FU visit,approx. up to 6 months. Add'l urinalysis in Cycle 1 Days 8 and 22. Each cycle is 28 days.
|
Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes in vital signs from baseline of vital sign examinations.
Time Frame: Screening (Days -28 to -1), Cycle 1 Days 1, 8, 15 and 22, Day 1 of each subsequent cycle, the end of treatment visit and the 30-day safety follow-up visit, approximately up to 6 months. Each cycle is 28 days.
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Clinically notable elevated values: Systolic blood pressure (BP): ≥ 160 mmHg and an increase ≥ 20 mmHg from baseline; Diastolic BP: ≥ 100 mmHg and an increase ≥ 15 mmHg from baseline; Heart rate : ≥ 120 beats/min (bpm) with increase from baseline of ≥ 15 bpm; Weight (kg) increase from baseline of ≥ 10%; Body temperature(°C) ≥ 37.5°C).
Clinically notable low values: Systolic BP: ≤ 90 mmHg with decrease from baseline of ≥ 20 mmHg; Diastolic BP: ≤ 50 mmHg with decrease from baseline of ≥ 15 mmHg; Heart rate: ≤ 50 bpm with decrease from baseline of ≥ 15 bpm; Weight: ≥ 20% decrease from baseline; Body temperature [°C]: ≤ 36 °C.
Number of participants with TEAEs related to notable changes to the vital signs after the start of study drug will be reported.
|
Screening (Days -28 to -1), Cycle 1 Days 1, 8, 15 and 22, Day 1 of each subsequent cycle, the end of treatment visit and the 30-day safety follow-up visit, approximately up to 6 months. Each cycle is 28 days.
|
Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes from baseline of 12-lead electrocardiograms (ECGs)
Time Frame: Screening (Days -28 to -1), Cycle 1 Day 8, 15 and 22, Day 1 of each subsequent even cycle (Cycle 2, 4, 6, …) and the end of treatment visit, approximately up to 6 months. Each cycle is 28 days.
|
12-lead ECGs will be obtained using an internationally recognized 12-lead cardiograph.
Clinically notable ECG values: QT [millisecond (ms)] and QT interval (ms) corrected for heart rate using Fridericia's formula (QTcF) intervals (ms): increase from baseline > 30 ms; increase from baseline > 60 ms, new > 450 ms, new > 480 ms, new > 500 ms.
Heart rate (beats/min): increase from baseline > 25% to a value > 100 bpm, decrease from baseline > 25% and to a value < 50 bpm.
Number of participants with TEAEs related to abnormal or notable changes to ECG parameters after the start of study drug will be reported.
|
Screening (Days -28 to -1), Cycle 1 Day 8, 15 and 22, Day 1 of each subsequent even cycle (Cycle 2, 4, 6, …) and the end of treatment visit, approximately up to 6 months. Each cycle is 28 days.
|
Incidence of targeted treatment emergent adverse events (TEAEs) of special interest
Time Frame: Cycle 1 Day 1 through safety follow-up visit (30 days after end of treatment (EOT) visit or 7 days after end EOT visit/last dose if EOT not performed), approximately up to 6 months.
|
Adverse event of special interest (AESI) are as follows: acute renal failure, cutaneous non-squamous cell carcinoma, cutaneous squamous cell carcinoma, melanomas, palmar-plantar erythrodysaesthesia syndrome, photosensitivity, rash, severe cutaneous adverse reactions, facial paresis, tachycardia, haemorrhage, hepatic failure, liver function test abnormalities, myopathy and uveitis-type events.
Number and percentage of participants with at least one event of any AESI and of each category of AESI will be reported in participants.
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Cycle 1 Day 1 through safety follow-up visit (30 days after end of treatment (EOT) visit or 7 days after end EOT visit/last dose if EOT not performed), approximately up to 6 months.
|
Plasma pharmacokinetics (PK) of encorafenib: Area under the curve (AUC) after single and repeated administration of encorafenib
Time Frame: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle is 28 days.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle is 28 days.
|
|
Plasma pharmacokinetics (PK) of encorafenib metabolite (LHY746): Area under the curve (AUC) after single and repeated administration of encorafenib
Time Frame: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle is 28 days.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle is 28 days.
|
|
Plasma pharmacokinetics (PK) of encorafenib: Maximum concentration (Cmax) after single and repeated administration of encorafenib
Time Frame: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle is 28 days.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle is 28 days.
|
|
Plasma pharmacokinetics (PK) of encorafenib metabolite (LHY746): Maximum concentration (Cmax) after single and repeated administration of encorafenib
Time Frame: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle is 28 days.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle is 28 days.
|
|
Plasma pharmacokinetics (PK) of encorafenib: Minimum concentration (Cmin) after single and repeated administration of encorafenib
Time Frame: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle is 28 days.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle is 28 days.
|
|
Plasma pharmacokinetics (PK) of encorafenib metabolite (LHY746): Minimum concentration (Cmin) after single and repeated administration of encorafenib
Time Frame: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle is 28 days.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle is 28 days.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 27, 2021
Primary Completion (Actual)
May 6, 2022
Study Completion (Actual)
May 6, 2022
Study Registration Dates
First Submitted
June 24, 2021
First Submitted That Met QC Criteria
August 5, 2021
First Posted (Actual)
August 12, 2021
Study Record Updates
Last Update Posted (Actual)
June 10, 2022
Last Update Submitted That Met QC Criteria
June 9, 2022
Last Verified
June 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- W00090GE102
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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