Clinical trial NCT01828099
Conditions: Non-Small Cell Lung Cancer
Keywords: Non-Small Cell Lung Cancer NSCLC ALK LDK378 Non-small cell lung carcinoma (NSCLC) treatment of lung cancer after first metastasis lung cancer lung adenocarcinoma Non small cell lung carcinoma Non small cell lung cancer non-squamous non-small cell lung cancer
Sponsor: Novartis Pharmaceuticals
Start date: 2013-07-09; Completion date: 2024-01-07
Enrollment: 376 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To compare the efficacy and safety of ceritinib with standard first-line chemotherapy (pemetrexed plus cisplatin or carboplatin) in patients with stage IIIB (not candidates for definitive multimodality therapy) or stage IV, non-squamous non-small cell lung cancer (NSCLC) harboring a confirmed anaplastic lymphoma kinase (ALK) rearrangement, using the Ventana immunohistochemistry (IHC) test.

Detailed description:
This was an open-label, randomized, global, Phase III study that compared the efficacy and safety of ceritinib to standard first-line chemotherapy in patients with advanced (NSCLC) harboring ALK rearrangement. The confirmation of ALK rearrangement was done using the ICH test by a Novartis designated central laboratory. Prior to the study, patients had not received any previous systemic, anti-cancer therapy, including ALK inhibitors, for newly diagnosed advanced non-squamous NSCLC.

The patients were randomized in a 1:1 ratio to either receive ceritinib (750 mg once daily, fasted) or chemotherapy. The chemotherapy regimen consisted of a platinum-based doublet with pemetrexed followed by pemetrexed maintenance in patients without progressive disease after 4 cycles.

Treatment was continued until the blinded independent review committee (BIRC) confirmed disease progression based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), occurrence of unacceptable toxicity, or meeting other discontinuation criteria. Patients in either arm were permitted to continue the assigned study treatment beyond BIRC-confirmed disease progression in case of continued clinical benefit, as determined by the Investigator.

All patients who discontinued treatment during the treatment phase for reasons other than death, lost to follow-up, pregnancy or disease progression entered the post-treatment follow-up period until disease progression, withdrawal of consent or death.

In the chemotherapy arm, patients were allowed to switch and receive ceritinib after BIRC-confirmed disease progression (extension-treatment period).

Arms: arm 1: Ceritinib administered continuously through oral dosing at a dosage of 750 mg once daily in fasted state. arm 2: Pemetrexed plus cisplatin or carboplatin (based on Investigator's choice) for 4 cycles (Induction) followed by pemetrexed as single agent (Maintenance)
Interventions: intervention 1: Ceritinib intervention 2: Pemetrexed intervention 3: Cisplatin intervention 4: Carboplatin
Intervention descriptions: intervention 1: Ceritinib was administered orally once-daily fasted at a dose of 750 mg capsules on a continuous dosing schedule. intervention 2: Pemetrexed was administered at a dose of 500 mg/m\^2 as an intravenous (iv) infusion on Day 1 of each 21-day cycle intervention 3: Cisplatin was administered by iv infusion at a dose of 75 mg/m\^2 every 21 days for up to 4 cycles. intervention 4: Carboplatin was administered as iv infusion (AUC 5-6) every 21 days up to 4 cycles

Protocol documents: