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Advanced Non-small Cell Lung CancerPhase 1NCT02964689

Binimetinib in Addition to Standard Chemotherapy in KRAS Mutated NSCLC.

A Phase 1 study testing Binimetinib, Pemetrexed and Cisplatin in people with Advanced Non-small Cell Lung Cancer and KRAS Gene Mutation, run by Swiss Cancer Institute at 4 sites in Switzerland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The aim is to determine the recommended phase 2 dose (RP2D) of binimetinib in combination with pemetrexed and cisplatin, and to demonstrate that the combination is feasible and has preliminary activity in previously untreated patients with advanced NSCLC and documented KRAS mutations. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Binimetinib, Pemetrexed and Cisplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
4 sitesSwitzerland
Study dates
12 Apr 2017to 2 Jul 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

4 sites in 1 country.

Switzerland4 sites

  • Universitaetsspital Basel

    Basel, 4031

  • IOSI Ospedale Regionale di Bellinzona e Valli

    Bellinzona, 6500

  • Kantonsspital Graubuenden

    Chur, CH-7000

  • Kantonsspital St. Gallen

    Sankt Gallen, 9007

Other trials in Switzerland

About this study

Official title: Binimetinib, Pemetrexed and Cisplatin, Followed by Maintenance With Binimetinib and Pemetrexed, in Patients With Advanced Non-small Cell Lung Cancer NSCLC With KRAS Mutations. A Multicenter Phase IB Trial.

The aim is to determine the recommended phase 2 dose (RP2D) of binimetinib in combination with pemetrexed and cisplatin, and to demonstrate that the combination is feasible and has preliminary activity in previously untreated patients with advanced NSCLC and documented KRAS mutations.

Read the detailed description

There is a need for more effective therapies for patients with advanced NSCLC driven by the RAS/MEK/ERK pathway. These tumors are generally aggressive, are almost exclusively of non-squamous histology, and represent the largest group of patients with advanced NSCLC harboring specific driver mutations in Western populations.

Based on recent preclinical and clinical evidence, mitogen-activated protein kinase kinase (MEK)-inhibition plus first-line chemotherapy is a promising new treatment for patients with NSCLC and KRAS [v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog] mutations.

Binimetinib is a medication without marketing authorization. Pemetrexed and cisplatin have marketing authorization in Switzerland and in EU for the treatment of non-small cell lung cancer (NSCLC) and will be administered as standard backbone treatment according to their Swissmedic-approved indication, dose and route of administration. Binimetinib, pemetrexed and cisplatin are IMP in the context of this phase I trial.

Being tested
Binimetinib, Pemetrexed, Cisplatin
Keywords
Advanced non-small cell lung cancer, KRAS mutations, Binimetinib, Pemetrexed, Cisplatin, Phase IB trial
Medical subject headings
Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BinimetinibDrug

    Also called MEK162

    Binimetinib will be administered in combination with pemetrexed and cisplatin (induction therapy), and with pemetrexed only (maintenance therapy), during the first 2 weeks of each cycle. Cycles will be repeated every 21 days.

  • PemetrexedDrug

    Pemetrexed 500 mg/m2 i.v. is applied on day 1 of each cycle, before cisplatin administration

  • CisplatinDrug

    Cisplatin 75 mg/m2 i.v. is applied on day 1 of each induction therapy cycle. The drug must be administered after pemetrexed infusion

Study groups in NCT02964689
Study groupRoleWhat they receive
Combination of binimetinib, pemetrexed and cisplatinExperimentalThe trial consists of two parts: * Part 1: dose escalation based on the 3+3 design with 2 doses of binimetinib * Part 2: expansion cohort at the recommended maximum tolerated dose (MTD) level of binimetinib
Receives: Drug: Binimetinib; Drug: Pemetrexed; Drug: Cisplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose-limiting toxicities (DLTs)

    A DLT is defined as an AE or abnormal laboratory value assessed as at least possibly related to trial treatment (binimetinib in combination with pemetrexed and cisplatin), which occurs ≤ 21 days following the first dose of trial treatment during cycle 1.

    Measured: within 21 days from the first dose

Secondary outcomes (4)

  1. Objective response (OR)

    OR will include complete and partial responses based on RECIST 1.1 criteria. Best response will be the best result by investigator and RECIST 1.1 in the planned follow-up CT scans.

    Measured: at 30 months after start of trial

  2. Progression-free survival (PFS)

    PFS will be calculated from registration until documented tumor progression according to RECIST 1.1 or death due to any reason, whichever occurs first.

    Measured: at 30 months after start of trial

  3. Overall survival (OS)

    OS will be calculated from registration until death due to any reason.

    Measured: at 30 months after start of trial

  4. Adverse events (AEs)

    AEs will be assessed according to NCI CTCAE V.4.03.

    Measured: at 30 months after start of trial

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Nov 2016 (estimated)
  2. Study start12 Apr 2017
  3. Primary completion2 Jul 2021
  4. Study completion2 Jul 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02964689
Sponsor's protocol ID
SAKK 19/16
Status last verified
Jul 2021
First submitted
14 Nov 2016
Last updated
14 Jul 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Binimetinib, Pemetrexed and Cisplatin in people with Advanced Non-small Cell Lung Cancer and KRAS Gene Mutation, run by Swiss Cancer Institute at 4 sites in Switzerland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting toxicities (DLTs) (time frame: within 21 days from the first dose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02964689.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2021.

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