Content - SAKK 19/16

SAKK 19/16 - Dosage of a new targeted drug for the treatment of lung cancer

This trial is investigating whether binimetinib in combination with standard chemotherapy pemetrexed and cisplatin, followed by maintenance therapy with binimetinib and pemetrexed, is effective and tolerated in patients with metastatic KRAS-mutated non-small cell lung cancer.  

Non-small cell lung cancer is a type of cancer that grows and forms metastases more slowly than small cell lung cancer. In KRAS-mutated lung cancer the KRAS gene is mutated. Binimetinib is a targeted substance that inhibits the activation of KRAS-mutated tumour cells. This substance has been used worldwide in patients with various types of cancer, but not in combination with standard chemotherapy. In the SAKK 19/16 trial, the dosage of binimetinib will be determined for subsequent research projects.  

During the trial, we will also be collecting blood samples in order to obtain a better understanding of this disease, its prognosis and treatment. We intend to store this biological material in a biobank, because such residual material and the health-related data are very valuable for biomedical research.

Study chair:

PD Dr. med. Martin Früh, Cantonal Hospital of St.Gallen, +41 71 494 10 68

  • Contacts at the hospitals

  • Exclusion criteria

    • NSCLC with any additional small cell carcinoma (SCLC) component by local diagnostic pathology report.

    • Meningeosis carcinomatosa, symptomatic or untreated central nervous system (CNS) metastases. Patients with treated, controlled CNS metastases can be enrolled 2 weeks after the end of radiotherapy if asymptomatic (no residual neurologic deficits) and no longer on corticosteroids.

    • Previous or concurrent malignancy with the following exceptions:

      • adequately treated basal cell or squamous cell carcinoma of the skin (adequate wound healing is required prior registration),
      • in situ carcinoma of the cervix, treated curatively and without evidence of recurrence for at least 5 years prior registration,
      • superficial bladder cancer, prostate intraepithelial neoplasm, other noninvasive or indolent malignancy, or other solid tumor treated curatively and without evidence of recurrence for at least 5 years prior registration.
    • Leptomeningeal disease.

    • Concurrent radiotherapy (patients with prior radiotherapy other than for brain metastases ≥ 7 days prior to registration can be enrolled).

    • Previous systemic therapy for advanced NSCLC; previous adjuvant or neoadjuvant chemotherapy allowed if last dose was administered at least 6 months ago.

    • Major surgery within 3 weeks before registration.

    • Concurrent treatment with any other experimental drug or other anticancer therapy.

    • Impaired cardiovascular function or clinically severe or uncontrolled cardiovascular diseases, including any of the following: 

      • congestive heart failure NYHA III or IV,
      • history of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) < 6 months prior to registration,
      • symptomatic chronic heart failure (G2 or higher), history or current evidence of clinically significant cardiac arrhythmia requiring medication and/or conduction abnormality < 6 months prior to registration except atrial fibrillation and paroxysmal supraventricular tachycardia.
    • Uncontrolled arterial hypertension defined as persistent elevation of systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg despite medical treatment.

    • History or current evidence of retinal vein occlusion (RVO) or current risk factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyper-viscosity or hypercoagulability syndromes); history of retinal degenerative disease.

    • History of Gilbert's syndrome.

    • Neuromuscular disorders that are associated with elevated creatine phosphokinase (CPK; e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).

    • Neuropathy (> G1) or hearing impairment/ tinnitus (> G1).

    • Impairment of gastrointestinal function or gastrointestinal disease (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).

    • History of thromboembolic or cerebrovascular events within 6 months prior to registration, including transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis or pulmonary emboli.

    • Known history of acute or chronic pancreatitis.

    • History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) within 12 months prior to registration.

    • Known positive serology for HIV (human immunodeficiency virus), active hepatitis B, and/or active hepatitis C infection.

    • Active infection within 14 days prior to registration.

    • Planning on embarking on a new strenuous exercise regimen after first dose of binimetinib (NB: muscular activities, such as strenuous exercise, that can result in significant increases in plasma CPK levels should be avoided while on binimetinib treatment).

    • Known lactose intolerance.

    • Known hypersensitivity to the trial drugs or hypersensitivity to any other component of the trial treatment, including premedication.

    • Any concomitant drugs contraindicated for use with pemetrexed and cisplatin according to the Swissmedic-approved current product information or with binimetinib according to the latest version of the Investigator's Brochure.

    • Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.

  • Inclusion criteria

    • Written informed consent according to the Swiss HRA and ICH-GCP regulation before registration and prior to any trial-specific procedure.
    • Histologically or cytologically confirmed diagnosis of NSCLC, predominantly non-squamous subtype (adenocarcinoma, large cell carcinoma, NOS).
    • Locally advanced or metastatic stage III-IV disease according to the 7th TNM classification, ineligible for curative treatment.
    • Presence of KRAS exon 2 or 3 (codon 12, 13 or 61) mutations by local testing (concomitant EGFR and ALK mutations are excluded).
    • CT scan showing measurable disease, which is defined as at least one lesion that can be measured in at least one dimension (non-nodal lesions ≥10 mm in longest diameter, lymph nodes ≥15 mm in short axis) according to RECIST 1.1.
    • Eligible for cisplatin-based chemotherapy and able to take oral medications.
    • WHO performance status 0-1.
    • Age from 18 to 75 years.
    • Adequate hematological values: hemoglobin ≥ 90 g/L, ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L.
    • Adequate hepatic function: total bilirubin ≤ 1.5 x ULN and < 34.2 μmol/L; ALT and alkaline phosphatase ≤ 2.5 x ULN.
    • Adequate renal function: calculated creatinine clearance ≥ 60 mL/min, according to the formula of Cockcroft-Gault.
    • Adequate cardiac function: left ventricular ejection fraction (LVEF) ≥ 50% as determined by echocardiogram; QTcF interval must be ≤ 480 ms.
    • Women with child-bearing potential are using effective contraception, are not pregnant or lactating and agree not to become pregnant during trial treatment and 6 months thereafter. A negative serum pregnancy test before inclusion into the trial is required for all women with child-bearing potential.
    • Men agree not to father a child during trial treatment and 6 months thereafter.

Locations for this trial:

Universitätsspital Basel
Petersgraben 4
0 4031 Basel
Istituto Oncologico della Svizzera Italiana IOSI
Via Ospedale
0 6500 Bellinzona
Kantonsspital Graubünden
Loëstrasse 170
7000 Chur
Kantonsspital St. Gallen
Rorschacher Strasse 95
0 9007 St. Gallen