STRIDER: A phase II Study evaluaTing intRacranial effIcacy of JDQ443 in patiEnts with KRAS G12C+ NSCLC and bRain metastases
- Conditions
- patients with KRAS G12C+ non small cell lung cancer and brain metastasesTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-505721-13-00
- Lead Sponsor
- niversity Hospital Maastricht
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 42
Signed informed consent must be obtained prior to participation in the study., Adequate organ function including the following laboratory values at the screening visit: · Absolute neutrophil count (ANC) = 1.5 x 109/L (without growth factor support), · Platelets = 100 x 109/L (without growth factor support), Hemoglobin (Hgb) = 6 mmol/l (= 9 g/dl) (7 days without transfusions or growth factor support), · Aspartate transaminase (AST) = 3 x ULN, · Alanine transaminase (ALT) = 3 x ULN, · Total bilirubin = 1.5 ULN, · Serum lipase = 1.5 x ULN, · Creatinine clearance = 60 mL/min by calculation using Cockcroft-Gault formula or based on 24-hour urine sample assessment., Participant is capable of swallowing study medication and following instructions regarding study treatment administration., Participant must be able to communicate with the Investigator and comply with the requirements of the study procedures., Participant is an adult = 18 years of age at the time of informed consent., ECOG performance status =2, Estimated life expectancy of 12 weeks or more, Metastatic (stage IV) NSCLC with the presence of a KRAS G12C mutation (local test, tissue as well as liquid biopsy allowed) and untreated or progressing asymptomatic BM (cohort A) or treated and stable BM (cohort B)., BM not in eloquent area (all patients have at least to be discussed with a neurologist, and preferably they are discussed in a neuro-oncology MDT). If treated with radiotherapy and stable, these patients are eligible for cohort B., Max BM size 2 cm in longest diameter (for each BM) for cohort A, For cohort A: at least one untreated brain metastasis = 5mm: a. Patients with largest measurable intracranial lesion =5 mm but <10 mm may be allowed to enroll upon agreement with the principal investigator (for patients with target lesions of = 5mm but <10 mm, 1.5 mm slice thickness brain MRI is required). b. Prior local treatment is permissible if completed at least 14 days prior to study enrollment and provided unequivocal progression in the lesion has since occurred or if new lesions have occurred. c. For at least 7 days prior to first dose of JDQ443 in this study: Patient must be asymptomatic from CNS metastases and on a stable dose of corticosteroids, with a maximum of 4 mg dexamethasone/day. Anti-epileptic dose should also be stable for 7 days, Participant must have recovered from all toxicities related to prior treatments to grade = 1 (CTCAE v 5.0). Exception to this criterion are alopecia and vitiligo of any grades.
Leptomeningeal metastasis (based on MRI or Cerebrospinal fluid (CSF) cytology, if strong suspicion despite negative MRI, CSF analysis should be done), History of interstitial lung disease or pneumonitis grade = 2., Current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (i.e. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes etc.)., Malignant disease, other than that is being treated in this study. Exceptions to this criterion include the following: malignancies that were treated curatively and have not recurred within two years prior to study treatment; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type., Any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator’s judgment cause unacceptable safety risks, contra-indicate participation in the clinical study or compromise compliance with the protocol (e.g. chronic pancreatitis, uncontrolled diabetes, hepatic disorders including cirrhosis)., Any other medical condition (such as active infection including known hepatitis or HIV, treated or untreated), which in the opinion of the Investigator represents an unacceptable risk for participation in the study., Any medical condition or prior surgical resection that may affect the absorption of the investigational drug. Examples of medical conditions that may affect investigational drug absorption include (but are not limited to) inflammatory bowel disease (i.e. ulcerative colitis, Crohn’s disease) and gastrointestinal disease such as ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, and malabsorption syndrome., Participants who are taking a prohibited medication (strong CYP3A inducers) that cannot be discontinued at least seven days prior to the first dose of study treatment and for the duration of the study, Use of any live vaccines against infectious diseases within four weeks of initiation of study treatment., Participant is concurrently using other anti-cancer therapy., Participation in any additional, parallel, investigational drug or device studies. Participation in non-interventional observational studies which will not influence the endpoints of the current studies is allowed (e.g. liquid biopsies, eNOSE, surveys)., Previous treatment with KRAS G12C inhibitor except if = 1 year has elapsed since last dose, Pregnant or breast-feeding women or women who plan to become pregnant or breast-feed during the study. Pregnant women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test., Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for 7 days after the last dose of JDQ443. Highly effective contraception methods include: · Total abstinence (when this is in line with the preferred and usual lifestyle of the participant). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. · Female bilateral tubal ligation, female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or total hysterectomy at least 6 weeks b
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method