Binimetinib in Addition to Standard Chemotherapy in KRAS Mutated NSCLC.

NCT02964689 | Completed Phase 1

• 1 other identifier: SAKK 19/16
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Advanced Non-small Cell Lung Cancer; KRAS Gene Mutation; Lung Cancer

Keywords

Advanced non-small cell lung cancer; KRAS mutations; Binimetinib; Pemetrexed; Cisplatin; Phase IB trial

Outcome Measures

Primary Outcomes (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.

  within 21 days from the first dose

Secondary Outcomes (4)

• Objective response (OR)

  at 30 months after start of trial

• Progression-free survival (PFS)

  at 30 months after start of trial

• Overall survival (OS)

  at 30 months after start of trial

• Adverse events (AEs)

  at 30 months after start of trial

Study Arms (1)

Combination of binimetinib, pemetrexed and cisplatin

EXPERIMENTAL

The 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

Drug: Binimetinib; Drug: Pemetrexed; Drug: Cisplatin

Interventions

Binimetinib DRUG

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.

Also known as: MEK162

Combination of binimetinib, pemetrexed and cisplatin

Pemetrexed DRUG

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

Combination of binimetinib, pemetrexed and cisplatin

Cisplatin DRUG

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

Combination of binimetinib, pemetrexed and cisplatin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Men agree not to father a child during trial treatment and 6 months thereafter.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (4)

Universitaetsspital Basel

Basel, 4031, Switzerland

Location

IOSI Ospedale Regionale di Bellinzona e Valli

Bellinzona, 6500, Switzerland

Location

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

binimetinib; Pemetrexed; Cisplatin

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Martin Früh, MD

  Cantonal Hospital of St. Gallen

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2016
• First Posted: November 16, 2016
• Study Start: April 12, 2017
• Primary Completion: July 2, 2021
• Study Completion: July 2, 2021
• Last Updated: July 14, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

CH (4)