Study of Safety and Preliminary Efficacy for LDK378 in Japanese Patients With Genetic Alterations in Anaplastic Lymphoma Kinase (ALK)

NCT01634763 | Completed Phase 1

• 1 other identifier: CLDK378X1101
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 3

Brief Summary

Estimation of the Maximum tolerated dose (MTD) and/or Recommended dose (RD) of LDK378 as a single agent when administered orally to Japanese patients with tumors characterized by genetic alterations in anaplastic lymphoma kinase (ALK)

Conditions

Tumors Characterized by Genetic Alterations in Anaplastic Lymphoma Kinase (ALK)

Keywords

Phase I, open-label, dose escalation, oral LDK378, Japanese patients with tumors characterized by ALK genetic alterations

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) and/or Recommended dose (RD) of LDK378

  As a single agent when administered orally to Japanese patients with tumors characterized by genetic alterations in ALK. The number of patients and category of Dose Limiting Toxicities (DLTs)

  During the first cycle (including the Pharmacokinetics [PK] run-in period) of LDK378 treatment. A treatment cycle consists of 21 days of daily dosing of LDK378.

Secondary Outcomes (9)

• The safety and tolerability of LDK378, including both acute and chronic toxicities

  Until disease progression or unacceptable toxicity occurs, or patient withdrawal

• Plasma concentration of LDK378

  PK run-in (0,0.5, 1, 2, 3, 4, 6, 8, 24, 48, and 72 hrs), Cycle1Day1 (0, 0.5, 1, 2, 3, 6, 8 and 24 hrs), Cycle2Day1 (0, 1, 2, 4, 6, 8 and 24 hrs), Day1 of every subsequent cycles up to Cycle6

• Preliminary anti-tumor activity of LDK378

  Baseline and every 6 weeks until disease progression or unacceptable toxicity occurs, or patient withdrawal

• PK parameter: AUClast

  PK run-in (0,0.5, 1, 2, 3, 4, 6, 8, 24, 48, and 72 hrs), Cycle1Day1 (0, 0.5, 1, 2, 3, 6, 8 and 24 hrs), Cycle2Day1 (0, 1, 2, 4, 6, 8 and 24 hrs), Day1 of every subsequent cycles up to Cycle6

• PK parameter: AUCtau

  PK run-in (0,0.5, 1, 2, 3, 4, 6, 8, 24, 48, and 72 hrs), Cycle1Day1 (0, 0.5, 1, 2, 3, 6, 8 and 24 hrs), Cycle2Day1 (0, 1, 2, 4, 6, 8 and 24 hrs), Day1 of every subsequent cycles up to Cycle6

Study Arms (2)

Dose-escalation

EXPERIMENTAL

Open-label dose escalation study of LDK378, administered orally in Japanese patients with tumors characterized by genetic alterations in anaplastic lymphoma kinase (ALK)

Drug: LDK378

Dose-expansion

EXPERIMENTAL

Open-label study of LDK378, administered orally in Japanese patients with tumors characterized by genetic alterations in ALK to see further safety, anti-tumor activity, and PK data in patients who has progressed since prior therapy with alectinib

Drug: LDK378

Interventions

LDK378 DRUG

Dose-escalation; Dose-expansion

Eligibility Criteria

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

You may qualify if:

• Patients with a locally advanced or metastatic malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists
• Only patients with tumors characterized by genetic alterations in ALK. For non-small cell lung cancer (NSCLC), an ALK translocation must be detected by Fluorescent in situ hybridization (FISH) in ≥15% of tumor cells. Local site documented results on ALK alteration are acceptable for enrollment of the patients. Central confirmation of local results is not required.
• Eastern Cooperative Oncology Group (ECOG) performance status grade ≤ 2
• Adequate organ function
• Dose-expansion part: Patients must have NSCLC that has progressed since prior therapy with alectinib. Alectinib must have been the only prior ALK inhibitor received by the patient prior to trial entry.

You may not qualify if:

• Patients with symptomatic Central Nerve System (CNS) metastases who are neurologically unstable or require increasing doses of steroids to control their CNS disease
• Patients with unresolved nausea, vomiting or diarrhea \> Common Terminology Criteria for Adverse Events (CTCAE) grade 1
• Other concurrent severe and/or uncontrolled medical conditions
• Patients who have been treated with chemotherapy or biologic therapy or other investigational agent \< 2 weeks prior to starting the daily dosing of the study drug for compounds with a half-life ≤ 3 days, and \< 4 weeks prior to starting the daily dosing of the study drug for compounds with a prolonged half-life (\< 6 weeks for patients that received nitrosoureas or mitomycin-C)
• Unresolved toxicity greater than CTCAE grade 1 or unstable toxicity from previous anti-cancer therapy or radiotherapy (excluding neurotoxicity, alopecia, ototoxicity, lymphopenia), or incomplete recovery from previous surgery, unless agreed by Novartis and the Principal Investigator and documented
• Patients who have received radiotherapy to lung within 4 weeks prior to starting the daily dosing of the study drug or patients who have not recovered from radiotherapy-related toxicities. For all other anatomic sites radiotherapy to a large volume (including whole brain radiotherapy) \< 2 weeks prior to starting the daily dosing of the study drug, and patients who have received radiotherapy to a small volume (including stereotactic radiotherapy to the CNS) \< 3 days prior to starting the study drug.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (3)

Novartis Investigative Site

Sunto-gun, Shizuoka, 411-8777, Japan

Location

Novartis Investigative Site

Koto, Tokyo, 135-8550, Japan

Location

Novartis Investigative Site

Fukuoka, 811-1395, Japan

Location

Related Publications (2)

• Ono A, Murakami H, Serizawa M, Wakuda K, Kenmotsu H, Naito T, Taira T, Koh Y, Ohde Y, Nakajima T, Endo M, Takahashi T. Drastic initial response and subsequent response to two ALK inhibitors in a patient with a highly aggressive ALK-rearranged inflammatory myofibroblastic tumor arising in the pleural cavity. Lung Cancer. 2016 Sep;99:151-4. doi: 10.1016/j.lungcan.2016.07.002. Epub 2016 Jul 5.

  PMID: 27565932 DERIVED

• Nishio M, Murakami H, Horiike A, Takahashi T, Hirai F, Suenaga N, Tajima T, Tokushige K, Ishii M, Boral A, Robson M, Seto T. Phase I Study of Ceritinib (LDK378) in Japanese Patients with Advanced, Anaplastic Lymphoma Kinase-Rearranged Non-Small-Cell Lung Cancer or Other Tumors. J Thorac Oncol. 2015 Jul;10(7):1058-66. doi: 10.1097/JTO.0000000000000566.

  PMID: 26020125 DERIVED

Related Links

• Results for CLDK378X1101 can be found on the Novartis Clinical Trial Results Website

MeSH Terms

Interventions

ceritinib

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2012
• First Posted: July 6, 2012
• Study Start: June 1, 2012
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: December 19, 2020

Record last verified: 2016-07

Locations

JP (3)