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LDK378 Versus Chemotherapy in Previously Untreated Patients With ALK Rearranged Non-small Cell Lung Cancer

Primary Purpose

Non-Small Cell Lung Cancer

Status

Active

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Ceritinib

Pemetrexed

Cisplatin

Carboplatin

About this trial

This is an interventional treatment trial for Non-Small Cell Lung Cancer focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patient has a histologically or cytologically confirmed diagnosis of non-squamous Non-small cell lung cancer (NSCLC) that is Anaplastic lymphoma kinase (ALK) positive as assessed by the Ventana Immunohistochemistry (IHC) test. The test will be performed at Novartis designated central laboratories.
Patient has newly diagnosed stage IIIB (who are not a candidate for definitive multimodality therapy) or stage IV NSCLC or relapsed locally advanced or metastatic NSCLC not previously treated with any systemic anti-cancer therapy (e.g. cytotoxic drugs, monoclonal antibody therapy, crizotinib or other ALK inhibitors, or other targeted therapies, either experimental or not), with exception of neo-adjuvant or adjuvant therapy
Patient has at least one measurable lesion as defined by RECIST 1.1.

Exclusion Criteria:

Patient with known hypersensitivity to any of the excipients of LDK378 (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate)
Patient with a history of severe hypersensitivity reaction to platinum containing drugs, pemetrexed or any known excipients of these drugs.
Patient with symptomatic central nervous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids within the 2 weeks prior to screening to manage CNS symptoms.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Ceritinib

Chemotherapy

Arm Description

Ceritinib patients were on continuous oral dosing of ceritinib 750 mg once daily in fasted state.

Chemotherapy patients (Induction per Investigator's choice) were on four 21-day cycles of Pemetrexed 500mg/m2 iv + Cisplatin 75 mg/m2 or Pemetrexed 500 mg/m2 iv + Carboplatin AUC 5-6 iv followed by Pemetrexed 500 mg/m2 every 21 days followed by Pemetrexed maintenance in non-progressors, etc (other usual rule to stop treatment).

Outcomes

Primary Outcome Measures

Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC)

PFS defined as time from date of randomization to date of first documented disease (as assessed by Blinded Independent Review Committee (BIRC) per RECIST 1.1) or date of death due to any cause

Secondary Outcome Measures

Overall Survival (OS)

OS defined as time from date of randomization to date of death due to any cause

Overall Response Rate (ORR)

ORR defined as the proportion of patients with a best overall response defined as Complete Response (CR) or Partial Response (PR) as evaluated by Blinded Independent Review Committee (BIRC) and by investigator assessment per RECIST 1.1

Duration of Response (DOR)

DOR defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to any cause

Disease Control Rate (DCR)

DCR defined as the proportion of patients with best overall response of CR, PR, or Stable Disease (SD)

Time to Response (TTR)

TTR defined as the time from date of randomization to date of first documented response (CR or PR)

Patient Reported Outcomes

The time to definitive deterioration from the date of randomization to the date of event for disease related symptoms.

Full Information

NCT ID

NCT01828099

First Posted

April 3, 2013

Last Updated

October 10, 2023

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01828099

Brief Title

LDK378 Versus Chemotherapy in Previously Untreated Patients With ALK Rearranged Non-small Cell Lung Cancer

Official Title

A Phase III Multicenter, Randomized Study of Oral LDK378 Versus Standard Chemotherapy in Previously Untreated Adult Patients With ALK Rearranged (ALK-positive), Stage IIIB or IV, Non-squamous Non-small Cell Lung Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

July 9, 2013 (Actual)

Primary Completion Date

June 24, 2016 (Actual)

Study Completion Date

December 15, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The primary purpose of the study was to compare the antitumor activity of LDK378 versus reference chemotherapy. Patients in the chemotherapy arm were allowed to cross-over to LDK378 after confirmed progressive disease (PD).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

376 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ceritinib

Arm Type

Experimental

Arm Description

Ceritinib patients were on continuous oral dosing of ceritinib 750 mg once daily in fasted state.

Arm Title

Chemotherapy

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Ceritinib

Other Intervention Name(s)

LDK378

Intervention Description

Ceritinib was administered orally once-daily fasted at a dose of 750 mg capsules on a continuous dosing schedule. Ceritinib (LDK378) was the investigational treatment and is referred to as the investigational study treatment/drug.

Intervention Type

Drug

Intervention Name(s)

Pemetrexed

Intervention Description

Pemetrexed was administered at a dose of 500 mg/m2 as an iv infusion on Day 1 of each 21-day cycle to patients randomized to the chemotherapy arm.

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Intervention Description

Cisplatin was administered by IV at a dose of 75 mg/m2 every 21 days for up to 4 cycles.

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Intervention Description

Carboplatin was administered as iv infusion (AUC 5-6) every 21 days up to 4 cycles

Primary Outcome Measure Information:

Title

Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC)

Description

PFS defined as time from date of randomization to date of first documented disease (as assessed by Blinded Independent Review Committee (BIRC) per RECIST 1.1) or date of death due to any cause

Time Frame

from the date of randomization to the date of first radiologically documented disease progression or death due to any cause (assessed every 6 weeks up to approximately 34 months)

Secondary Outcome Measure Information:

Title

Overall Survival (OS)

Description

OS defined as time from date of randomization to date of death due to any cause

Time Frame