Preoperative Ceritinib (LDK378) in Glioblastoma Multiforme and CNS Metastasis

NCT02605746 | Completed Early Phase 1

• 1 other identifier: PHX15BN068
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is two parallel studies to examine pharmacokinetic (PK), pharmacodynamic (PD), and pharmacogenetic (PG) endpoints following short-interval therapy (10-14) daily doses without dose reduction and interruption) with the ALK (anaplastic lymphoma kinase) small-molecule inhibitor, ceritinib. The Phase 0 study will investigate:

1. 1.first recurrence GBM patients and
2. 2.patients with CNS metastases from solid tumors such as, but not limited to, NSCLC (non-small cell lung cancer) and melanoma.

Conditions

Glioblastoma; Brain Metastases

Outcome Measures

Primary Outcomes (3)

• Plasma Concentration

  Plasma concentration of Ceritinib after 10-14 oral doses of 750 mg. Will be summarized using descriptive statistics.

  at pre-dose on day 10-14(Day 0), 0.5, 1, 2, 4, 6, 8, and 24 hours following single dose of CERITINIB

• Cerebrospinal Concentration

  Cerebrospinal concentration of Ceritinib. Will be summarized using descriptive statistics.

  collected intraoperatively at 2-4, 4-8, and 22-26 hours following single dose of CERITINIB relative to the final dose on day 10-14

• Intratumoral Concentration

  Intratumoral concentration of Ceritinib. Will be summarized using descriptive statistics.

  collected intraoperatively at 2-4, 4-8, and 22-26 hours following single dose of CERITINIB relative to the final dose on day 10-14

Secondary Outcomes (4)

• Tumor Tissue

  at baseline(archival) and up to 26 hours post dosing

• Tumor Cells in M-Phase

  at baseline and up to 26 hours post dose CERITINIB

• Double Strand DNA

  at baseline and up to 26 hours post dose CERITINIB

• Tissue Concentration

  2-4, 4-8, and 22-26 hours post dosing relative to the final Day 10 dose, as compared to the immediate pre-operative MRI scan

Study Arms (3)

2-4 hours

EXPERIMENTAL

All patients will be orally-administered 10-14 doses of ceritinib 750mg with the final dose occurring at one of three intervals before brain tumor resection. This arm has the last ceritinib dose 2-4 hours prior to craniotomy for tumor resection.

Drug: ceritinib 750mg

4-8 hours

EXPERIMENTAL

All patients will be orally-administered 10-14 doses of ceritinib 750mg with the final dose occurring at one of three intervals before brain tumor resection. This arm has the last ceritinib dose 4-8 hours prior to craniotomy for tumor resection.

Drug: ceritinib 750mg

22-26 hours

EXPERIMENTAL

All patients will be orally-administered 10-14 doses of ceritinib 750mg with the final dose occurring at one of three intervals before brain tumor resection. This arm has the last ceritinib dose 22-26 hours prior to craniotomy for tumor resection.

Drug: ceritinib 750mg

Interventions

ceritinib 750mg DRUG

2-4 hours; 22-26 hours; 4-8 hours

Eligibility Criteria

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

You may qualify if:

• One prior resection of GBM or MRI evidence of solid tumor CNS metastasis
• All GBM and NSLC metastases must be ALK+
• Eastern Cooperative Oncology Group performance status ≤2
• Archival tumor tissue block available for research use
• Ability to understand written informed consent
• Recovery from toxicities related to prior anticancer therapies to ≤ grade 2 (CTCAE v 4.03). Exception: patients with any grade alopecia
• The following lab criteria are met:
• Absolute neutrophil count ≥ 1.5 x 10(9th power)/L
• Hemoglobin ≥ 8 g/dL
• Platelets ≥ 75 x 10(9th power)/L
• Serum total bilirubin ≤ 1.5 x upper limit of normal(ULN), except for patients with Gilbert's syndrome who may be included if total bilirubin ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
• Aspartate transaminase (AST) \< 3.0 x ULN, except for patients with liver metastasis, who are only included if AST \< 5 x ULN; alanine transaminase (ALT) \< 3.0 x ULN, except for patients with liver metastasis, who are only included if ALT \< 5 x ULN
• Creatinine clearance ≥ 30 mL/min
• Patient has following lab values or has lab values corrected with supplements to be within normal limits at screening:
• Potassium ≥ LLN

You may not qualify if:

• Co-morbid condition(s) that prevent safe surgical treatment
• Active infection or fever \> 38.5°C
• Patients with known hypersensitivity to any excipients of ceritinib
• Prior therapy with ceritinib
• Patients with known history of extensive disseminated bilateral interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, obliterative bronchiolitis, and clinically significant radiation pneumonitis (affecting activities of daily living or requiring therapeutic intervention)
• Clinically significant uncontrolled heart disease and/or recent cardiac event (within 6 months), such as:
• history of documented congestive heart failure (New York Heart Association functional classification III-IV);
• uncontrolled hypertension defined by a Systolic Blood Pressure ≥ 160 mm Hg and/or Diastolic Blood Pressure ≥ 100 mm Hg, with or without antihypertensive medication
• initiation or adjustment of antihypertensive medication(s) is allowed prior to screening;
• ventricular arrhythmias; supraventricular and nodal arrhythmias not controlled with medication;
• other cardiac arrhythmia not controlled with medication;
• corrected QTc \> 450 msec using Fridericia correction on the screening ECG
• Impaired GI function or GI disease that may alter absorption of ceritinib or inability to swallow up to five ceritinib capsules daily
• Ongoing GI adverse events \> grade 2 (e.g. nausea, vomiting, or diarrhea) at the start of the study
• Receiving medications that meet 1 of the following criteria and cannot be discontinued at least 1 week prior to start of treatment with ceritinib and for the duration of participation:

Sponsors & Collaborators

• St. Joseph's Hospital and Medical Center, Phoenix: lead
• Novartis: collaborator
• Wayne State University: collaborator
• Translational Genomics Research Institute: collaborator

Study Sites (1)

Barrow Brain and Spine

Phoenix, Arizona, 85013, United States

Location

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

ceritinib

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Nader Sanai, MD

  Barrow Brain and Spine, Phoenix AZ

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Clinician

Study Record Dates

• First Submitted: September 8, 2015
• First Posted: November 16, 2015
• Study Start: February 17, 2016
• Primary Completion: November 29, 2018
• Study Completion: July 12, 2019
• Last Updated: December 11, 2020

Record last verified: 2020-12

Locations

US (1)