Study of Safety and Efficacy of LEE011 and Ceritinib in Patients With ALK-positive Non-small Cell Lung Cancer.

NCT02292550 | Completed Phase 1 FDA Drug

• 1 other identifier: CLEE011X2110C
• Study Type: interventional
• Target: 27
• Locations: 6 countries
• Sites: 8

Brief Summary

This was a Phase Ib/II study of the ALK inhibitor ceritinib in combination with the CDK4/6 inhibitor LEE011 in patients with ALK-positive non-small cell lung cancer. The purpose of the study was to determine the MTD/RP2D of the LEE011 and ceritinib combination and evaluate whether the combination was safe and had beneficial effects in ALK-positive advanced non-small cell lung cancer patients. This trial did not progress to Phase II. Trial population terminated before reaching Phase II

Conditions

Non-small Cell Lung Cancer

Keywords

Non-small cell lung cancer; ALK translocation; ALK-positive; NSCLC; LEE011; CDK4/6 inhibitor; EML4-ALK; cancer

Outcome Measures

Primary Outcomes (3)

• Incidence rate of dose limiting toxicities (DLTs) during the first cycle of treatment (Phase Ib )

  Maximum Tolerated Dose(s) (MTD(s)) and/or recommended phase 2 dose (RP2D(s)) and schedule of LEE011 in combination with ceritinib in ALK-positive non-small cell lung cancer (NSCLC) patients. Cycle = 28 days

  1 month

• Overall Response Rate (ORR) as per RECIST v1.1

  Preliminary anti-tumor activity of the LEE011 and ceritinib combination

  Up to 24 months

• Exposure to LEE011 and ceritinib (Phase Ib )

  Measurement of pharmacokinetics (PK) parameters (AUC0-24h at C1D15)

  Up to 6 months

Secondary Outcomes (10)

• Overall Response Rate (ORR) - Phase Ib & II

  Up to 24 months

• Frequency of adverse events/serious adverse events

  Up to 24 months

• PK parameters of LEE011 and ceritinib

  Up to 6 months

• Frequency of dose interruptions and dose reductions (phase lb & ll)

  Up to 24 months

• Progression free survival (PFS) per RECIST v1.1 - Phase Ib & II

  Up to 24 months

Study Arms (5)

Ribociclib 100 mg + Ceritinib 300 mg

EXPERIMENTAL

LEE011 capsule for oral use (ribociclib) and Ceritinib for oral use

Drug: Ribociclib; Drug: Ceritinib

Ribociclib 100 mg + Ceritinib 450 mg

EXPERIMENTAL

LEE011 capsule for oral use (ribociclib) and Ceritinib for oral use

Drug: Ribociclib; Drug: Ceritinib

Ribociclib 200 mg + Ceritinib 300 mg

EXPERIMENTAL

LEE011 capsule for oral use (ribociclib) and Ceritinib for oral use

Drug: Ribociclib; Drug: Ceritinib

Ribociclib 200 mg + Ceritinib 450 mg

EXPERIMENTAL

LEE011 capsule for oral use (ribociclib) and Ceritinib for oral use

Drug: Ribociclib; Drug: Ceritinib

Ribociclib 300 mg + Ceritinib 450 mg

EXPERIMENTAL

LEE011 capsule for oral use (ribociclib) and Ceritinib for oral use

Drug: Ribociclib; Drug: Ceritinib

Interventions

Ribociclib DRUG

CDK 4/6 inhibitor

Also known as: LEE011

Ribociclib 100 mg + Ceritinib 300 mg; Ribociclib 100 mg + Ceritinib 450 mg; Ribociclib 200 mg + Ceritinib 300 mg; Ribociclib 200 mg + Ceritinib 450 mg; Ribociclib 300 mg + Ceritinib 450 mg

Ceritinib DRUG

ALK inhibitor

Also known as: LDK378, Zykadia

Ribociclib 100 mg + Ceritinib 300 mg; Ribociclib 100 mg + Ceritinib 450 mg; Ribociclib 200 mg + Ceritinib 300 mg; Ribociclib 200 mg + Ceritinib 450 mg; Ribociclib 300 mg + Ceritinib 450 mg

Eligibility Criteria

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

You may qualify if:

• Patients must be diagnosed with ALK-positive advanced NSCLC. The tumor must be ALK-positive as determined by ALK rearrangement in ≥15% of cells (as measured by FISH using the Vysis break-apart ALK probe) or by using the Ventana ALK IHC test. The analysis may be performed locally.
• Eastern cooperative oncology group (ECOG) performance status ≤ 2.
• Measurable disease as per RECIST v1.1
• Availability of tumor sample:
• For ALK inhibitor naïve patients:
• o A representative tumor sample must be submitted. An archival tumor specimen is acceptable
• For patients after progression on an ALK inhibitor:
• o A new tumor biopsy is required unless a biopsy performed after progression on the patient's most recent ALK inhibitor is available for submission For all patients a newly obtained tumor specimen must be submitted if no appropriate archival sample is available. In the event that no sample is available and a new biopsy cannot be obtained, enrollment may be considered after discussion with the sponsor.

You may not qualify if:

• For Phase I part:
• o Patients who have not previously received at least one line of therapy for ALK-positive NSCLC
• For Phase II part:
• Group A: prior therapy with any ALK inhibitor is not permitted.
• Group B: progression following any ALK inhibitor(s) other than ceritinib is required and the last dose of the ALK inhibitor must be no more than 60 days prior to the first dose of study drug. Prior ceritinib is not permitted.
• Group C: progression following ceritinib is required and the last dose of ceritinib must be no more than 60 days prior to the first dose of study drug.
• Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or require increasing doses of steroids or local CNS-directed therapy to control their CNS disease
• Patients with abnormal laboratory values during screening and on day 1 of pre-dose
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of ceritinib or LEE011
• Patients who are currently receiving treatment (that cannot be discontinued at least 1 week prior to the initiation of the study) with agents that are known to be any of the following: strong inducers or inhibitors of CYP3A4/5; sensitive substrates of CYP3A; substrates of CYP3A4/5 or CYP2C9 with a narrow therapeutic index.
• Patient has a history of pancreatitis or history of increased amylase or lipase that was due to pancreatic disease.
• Patient with impaired cardiac function or any clinically significant uncontrolled cardiac disease, and/or, cardiac repolarization abnormality, including any of the following:
• Clinically significant heart disease such as CHF requiring treatment (NYH grade ≥ 2), history of angina pectoris, myocardial infarction, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to study entry, documented cardiomyopathy, or left ventricular ejection fraction (LVEF) \< 50% as determined by multiple gated acquisition scan (MUGA) or echocardiogram (ECHO).
• Uncontrolled systolic blood pressure (SBP) ≥160 mmHg and/or diastolic blood pressure (DBP) ≥100 mmHg, with or without anti-hypertensive medication. Initiation or adjustment of antihypertensive medication (s) is allowed prior to screening, Systolic blood pressure (SBP) \<90 mmHg Standard 12-lead ECG values defined as the mean of the triplicate ECGs and assessed by central laboratory
• QTcF interval at screening \>450 msec (using Fridericia's correction)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (8)

Novartis Investigative Site

Boston, Massachusetts, 02114, United States

Location

Novartis Investigative Site

Marseille, 13385, France

Location

Novartis Investigative Site

Bologna, BO, 40138, Italy

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Seoul, Seocho Gu, 06591, South Korea

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Tainan, Taiwan ROC, 70403, Taiwan

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Related Links

• Results for CLEE011X2110C can be found on the Novartis Clinical Trial Results Website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms

Interventions

ribociclib; ceritinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This was a multi-center, open-label, dose finding, Phase Ib dose escalation study to estimate the maximum tolerated doses (MTD(s))

Study Record Dates

• First Submitted: November 12, 2014
• First Posted: November 17, 2014
• Study Start: May 14, 2015
• Primary Completion: September 26, 2018
• Study Completion: September 26, 2018
• Last Updated: December 17, 2020

Record last verified: 2019-07

Locations

KR (1); FR (1); US (1); IT (2); ES (1); TW (2)