Ceritinib in Combination With Stereotactic Ablative Radiation Metastatic Lung Adenocarcinoma

NCT02513667 | Terminated Phase 2 Results DMC

• 1 other identifier: STU 042015-076
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to see if Ceritinib can target ALK in non-small cell lung cancer and slow down cancer growth and prevent it from spreading.

Conditions

ALK-positive Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Number of days until disease progression or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

  Baseline until date of first observed disease progression or death, assessed up to 31.7 months.

Secondary Outcomes (6)

• Overall Survival

  at 12 months

• Time to 2nd Subsequent Stereotactic Ablative Radiation

  18 hours

• Time to 3rd Subsequent Stereotactic Ablative Radiation (SABR)

  3 months

• Number of Patients With CR/PR/Stable Disease for 6 Months

  At 6 months

• Number of Patients With CR/PR/Stable Disease for 12 Months

  at 12 months

Study Arms (2)

ALK-inhibitor naive patients

EXPERIMENTAL

Patients will receive ceritinib at a dose of 750 mg (150 mg capsules times 5 capsules once a day) for 10 weeks. Patient will stop taking Ceritinib 72 hours before SABR (Stereotactic ablative body radiation). They could get 1, 3 ,or 5 treatments on consecutive days with 18 hours between each treatment or every other day (doctor's determination). The patient may start taking Ceritinib again 72 hours after radiation is complete. Patient will continue to take certinib for up to 8 months. At Follow-Up treatment, patients will be contacted every 3 months for 9 months.

Drug: Ceritinib; Radiation: Stereotactic ablative body radiation

Patients recieved prior ALK inhibitor

EXPERIMENTAL

Patients will receive ceritinib at a dose of 750 mg (150 mg capsules times 5 capsules once a day) for 10 weeks. Patient will stop taking Ceritinib 72 hours before SABR (Stereotactic ablative body radiation). They could get 1, 3 ,or 5 treatments on consecutive days with 18 hours between each treatment or every other day (doctor's determination). The patient may start taking Ceritinib again 72 hours after radiation is complete. Patient will continue to take certinib for up to 8 months. At Follow-Up treatment, patients will be contacted every 3 months for 9 months.

Drug: Ceritinib; Radiation: Stereotactic ablative body radiation

Interventions

Ceritinib DRUG

Patients will receive ceritinib at a dose of 750 mg (150 mg capsules times 5 capsules once a day) for 10 weeks. Patient will stop taking Ceritinib 72 hours before SABR radiation. The patient may start taking Ceritinib again 72 hours after radiation is complete. Patient will continue to take certinib for up to 8 months.

ALK-inhibitor naive patients; Patients recieved prior ALK inhibitor

Stereotactic ablative body radiation RADIATION

Patients will receive study drug for 10 weeks. They could get 1, 3 ,or 5 treatments on consecutive days with 18 hours between each treatment or every other day (doctor's determination).

ALK-inhibitor naive patients; Patients recieved prior ALK inhibitor

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed diagnosis of lung adenocarcinoma that demonstrates ALK rearrangement as detected by the approved FISH test (Abbott Molecular Inc), using Vysis breakapart probes (defined as 15% or more positive tumor cells); or the Ventana IHC test. Evidence of rearrangement by gene sequencing tests such as FoundationOne or Caris will also be seen as evidence of ALK abnormality and meeting eligibility requirement.
• Patients with no prior ALK-inhibitor therapy will be placed in cohort A, those treated with one prior line of ALK-inhibitor (at any time) will enter cohort B.
• Patients will not have any other curative therapeutic option, such as radiation or surgery.
• WHO performance status 0-2.
• Age ≥18 years.
• Patients must have recovered from all toxicities related to any prior anticancer therapies to ≤ Grade 2 (CTCAE v 4.03), provided that any concomitant medication is given prior to initiation of treatment with ceritinib. Exception to this criterion: patients with any grade of alopecia are allowed to enter the treatment.
• Adequate organ function: the following laboratory criteria have been met:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Hemoglobin (Hgb) ≥ 8 g/dL
• Platelets ≥ 75 x 109/L
• Serum creatinine \<1.5 mg/dL and /or calculated creatinine clearance (using Cockcroft-Gault formula) ≥30 mL/min
• 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 or direct bilirubin ≤ 1.5 x ULN
• Aspartate transaminase (AST) \< 2.0 x ULN, except for patients with liver metastasis, who are only included if AST \< 3 x ULN; alanine transaminase (ALT) \< 2.0 x ULN, except for patients with liver metastasis, who are only included if ALT \< 3 x ULN
• Alkaline phosphatase (ALP) ≤5.0 x ULN
• Fasting plasma glucose ≤175 mg/dL (≤9.8 mmol/L)

You may not qualify if:

• Patients with known hypersensitivity to any of the excipients of ceritinib (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate).
• History of carcinomatous meningitis.
• Prior therapy with ceritinib.
• Patient has history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention).
• Patient who has received thoracic radiotherapy to lung fields ≤4 weeks prior to starting the study treatment or patients who have not recovered from radiotherapy-related toxicities. For all other anatomic sites (including radiotherapy to thoracic vertebrae and ribs) radiotherapy ≤2 weeks prior to starting the study treatment or has not recovered from radiotherapy-related toxicities. Palliative radiotherapy for bone lesions ≤2 weeks prior to starting study treatment is allowed.
• Patient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months), such as:
• unstable angina within 6 months prior to screening;
• myocardial infarction within 6 months prior to screening;
• history of documented congestive heart failure (New York Heart Association functional classification III-IV);
• uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 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 QT (QTcF) \>470 ms using Fridericia's 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. Although, patients unable to swallow capsules will be allowed to participate in this study, by following the specific instructions on making a slurry of the medication.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Interventions

ceritinib

Results Point of Contact

• Title: Dr. Sawsan Rashdan
• Organization: UT Southwestern Medical Center

Sawsan.Rashdan@UTSouthwestern.edu

214-648-4180

Study Officials

• Saad Khan, MD

  UT Southwetern Medical Center-Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: July 30, 2015
• First Posted: July 31, 2015
• Study Start: November 1, 2015
• Primary Completion: May 29, 2020
• Study Completion: May 29, 2021
• Last Updated: February 3, 2023
• Results First Posted: December 17, 2021

Record last verified: 2023-01

Locations

US (1)