- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03681483
RO5126766 for Patients With Advanced KRAS-Mutant Lung Cancer
October 2, 2023 updated by: Memorial Sloan Kettering Cancer Center
A Phase 1 Trial of RO5126766 (CH5126766) in Patients With Advanced KRAS-Mutant Lung Adenocarcinomas
The purpose of this study is to test the safety of RO5126766 at different doses to find out what effects, if any, it has on people with advanced lung cancer who have previously received treatment with a PD-1 or PD-L1 inhibitor.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
15
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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Florida
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Miami, Florida, United States, 33143
- Miami Cancer Institute
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New York
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New York, New York, United States, 10065
- Memorial Sloan Kettering Cancer Center
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Pennsylvania
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Allentown, Pennsylvania, United States, 18103
- Lehigh Valley Health Network
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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
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Histologically or cytologically proven diagnosis of advanced NSCLC
- Documented presence of KRAS mutation
- Prior treatment with a PD-1/L1 inhibitor. Patients who were deemed not eligible for therapy with a PD-1/L1 inhibitor by their treating physician will also be eligible in the dose expansion phase.
- Prior treatment with chemotherapy
- Able to take oral medications
- Measurable and/or evaluable disease (RECIST 1.1) indicator lesion not previously irradiated
- Karnofsky performance status (KPS) ≥ 70% (ECOG of 0 or 1 also acceptable)
- Age≥ 18 years old
Hematological and biochemical indices within the ranges shown below Hematological and biochemical indices within the ranges shown below (These measurements must be performed within two weeks [Day 14 to Day 1] before the patient is entered into the trial).
- AST, ALT ≤ 2.5 x ULN - Total bilirubin ≤ 1.5 x ULN -Albumin≥2.5g/dL
- Creatinine < 1.5 x ULN OR calculated creatinine clearance ≥50mL/min
- Absolute neutrophil count (ANC) ≥ 1,200 cells/mm3
- Hemoglobin ≥9.0 g/dL
- Platelets ≥100,000/mm^3.
- A negative serum pregnancy test obtained within two weeks prior to the administration of the study drug in all women of child bearing potential
Exclusion Criteria:
- Patients with symptomatic brain metastasis requiring escalating doses of steroids
- Patients with grade 2 or greater diarrhea prior to study initiation despite maximal medical management
- History of any bowel disease including abdominal fistula, gastro-intestinal perforation
- History of acute pancreatitis within 1 year of study entry or history of chronic pancreatitis
- History of or ongoing alcohol abuse that, in the opinion of the treating physician, would compromise compliance or impart excess risks associated with study participation.
- Pregnant or lactating women
- Any type of systemic therapy (chemotherapy or experimental drugs) within 3 weeks of starting treatment on protocol (within 6 weeks for for nitrosoureas and mitomycin C)
- Radiotherapy within 2 weeks of starting treatment on protocol
- Prior treatment with MEK, RAF, or ERK inhibitor(s)
Significant uncontrolled or active cardiovascular disease, specifically including, but not restricted to:
- History of clinically significant (as determined by the treating physician) atrial arrhythmia
- Any ventricular arrhythmia
- History of congenital long QT syndrome.
- Abnormal QTc (≥ 450 msec in males and ≥ 470 msec in females)
- Ejection fraction ≤ 50% as assessed by echocardiogram
- Concurrent congestive heart failure
- Prior history of class III/ IV heart failure (New York Heart Association [NYHA]
- Myocardial infarction within the last 6 months
- Unstable angina or severe obstructive pulmonary disease
- Patients with baseline risk factors for central serous retinopathy or retinal vein occlusion such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure >21 mmHg Uncontrolled hypertension (Diastolic blood pressure > 100 mmHg; Systolic blood pressure > 150 mmHg).
- History of central serous retinopathy or retinal vein occlusion
- History of prior malignancy within 2 years that requires/ed treatment. Patients who are considered NED from a malignancy may be considered on a case by case basis.
- Known active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infections
- Patients exposed to CYP3A4 inhibitors within 7 days prior to the first dose and CYP3A4 inducers 7 days prior to the first dose. RO5126766 (CH5126766) is metabolised mainly by CYP3A4 therefore concomitant administration of strong inhibitors and inducers of cytochrome p450 3A4 enzymes is forbidden during study treatment (for a complete list please see Appendix A).
- Any other condition that, in the opinion of the investigator, may compromise the safety, compliance of the patient, or would preclude the patient from successful completion of the study
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 |
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Experimental: RO5126766 (CH5126766)
The study will begin with a standard 3+3 design.
The study will enroll 3 patients at the previously identified MTD15 (4mg two times per week on days 1 and 4).
The period of evaluation for dose limiting toxicity will be through completion of cycle 1.
If ≤1 of the 3 initial patients at the proposed dose experience a DLT, then 3 additional patients will be enrolled for a total of 6 planned patients at that dose level.
Otherwise, 3 patients will be enrolled at dose level -1.
If ≤ 1 of these patients experience a DLT, then 3 additional patients will be enrolled at the same dose level.
If more than 1 patient experiences a DLT in dose level -1, the study will be terminated.
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RO5126766 (CH5126766) is given 4mg twice weekly (Day 1 and Day 4 of each week) and should be taken by mouth on an empty stomach, either one hour before or two hours after a meal.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The maximum tolerated dose (MTD)
Time Frame: 1 year
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will be defined as the highest dose level at which ≤ 1 of 6 patients experienced a DLT.The NCI Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE) will be used to grade toxicities during the trial.
DLTs are defined as any toxicity occurring during the first cycle of treatment (i.e. 4 weeks), excluding toxicites clearly related to disease progression or disease-related processes.
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1 year
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overall response rate (dose expansion)
Time Frame: 1 year
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by RECIST 1.1
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1 year
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Gregory Riely, MD, PhD, Memorial Sloan Kettering Cancer Center
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
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)
October 31, 2018
Primary Completion (Estimated)
September 1, 2024
Study Completion (Estimated)
September 1, 2024
Study Registration Dates
First Submitted
September 20, 2018
First Submitted That Met QC Criteria
September 20, 2018
First Posted (Actual)
September 24, 2018
Study Record Updates
Last Update Posted (Actual)
October 3, 2023
Last Update Submitted That Met QC Criteria
October 2, 2023
Last Verified
October 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 18-285
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
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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