Clinical Trials /

RO5126766 for Patients With Advanced KRAS-Mutant Lung Cancer

NCT03681483

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: RO5126766 for Patients With Advanced KRAS-Mutant Lung Cancer
  • Official Title: A Phase 1 Trial of RO5126766 (CH5126766) in Patients With Advanced KRAS-Mutant Lung Adenocarcinomas

Clinical Trial IDs

  • ORG STUDY ID: 18-285
  • NCT ID: NCT03681483

Conditions

  • Advanced Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
RO5126766(CH5126766)RO5126766 (CH5126766)

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
RO5126766 (CH5126766)ExperimentalThe 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.
  • RO5126766

Eligibility Criteria

        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 one week [Day -7 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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The maximum tolerated dose (MTD)
Time Frame:1 year
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • RO5126766 (CH5126766)
  • KRAS-Mutant
  • 18-285

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