Ceritinib and Everolimus in Treating Patients With Locally Advanced or Metastatic Solid Tumors or Stage IIIB-IV Non-small Cell Lung Cancer

NCT02321501 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2014-0890NCI-2015-00062
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of ceritinib and everolimus in treating patients with solid tumors that have spread from where they started to nearby tissue or lymph nodes (locally advanced) or to other places in the body (metastatic) or stage IIIB-IV non-small cell lung cancer. Ceritinib and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

ALK Positive; Locally Advanced Malignant Solid Neoplasm; Metastatic Malignant Solid Neoplasm; ROS1 Gene Rearrangement; Stage IIIB Lung Non-Small Cell Cancer AJCC v7; Stage IV Lung Non-Small Cell Cancer AJCC v7

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) of ceritinib and everolimus, defined as the highest dose level in which 6 patients were treated with at most 1 experiencing a dose limiting toxicity

  MTD will be assessed.

  28 days

Secondary Outcomes (3)

• Response rate

  Up to 28 days after discontinuation of study drugs

• Progression-free survival

  Time from the start of the study until disease progressive or death, assessed up to 28 days after discontinuation of study drugs

• Pharmacokinetic parameters of everolimus and ceritinib

  Days 1, 15, and 21 (course 1), day 1 (course 2), day 1 (course 3), and at progression

Other Outcomes (1)

• Levels of biomarkers as measured by immunohistochemistry, multiplex technology and/or enzyme-linked immunosorbent assays

  Up to 28 days after discontinuation of study drugs

Study Arms (1)

Treatment (ceritinib, everolimus)

EXPERIMENTAL

Patients receive ceritinib PO QD and everolimus PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Ceritinib; Drug: Everolimus; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Ceritinib DRUG

Given PO

Also known as: LDK 378, LDK378, Zykadia

Treatment (ceritinib, everolimus)

Everolimus DRUG

Given PO

Also known as: 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001, RAD001, Votubia, Zortress

Treatment (ceritinib, everolimus)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ceritinib, everolimus)

Pharmacological Study OTHER

Correlative studies

Treatment (ceritinib, everolimus)

Eligibility Criteria

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

You may qualify if:

• For dose escalation cohort: patients with histologically or cytologically confirmed locally advanced or metastatic solid tumors who have failed at least one line of therapy
• For dose expansion cohort: patients with stage IIIB or IV ALK + NSCLC who have failed at least one line of therapy and are progressing on an ALK inhibitor; for dose expansion, patients who have ROS1 rearrangement testing by either next generation sequencing (NGS) or fluorescence in situ hybridization (FISH) will be eligible
• Absolute neutrophil count (ANC) \>= 1,500/microliter
• Platelets \>= 100,000/microliter
• Hemoglobin (Hgb) \>= 9 g/dL
• Creatinine =\< 1.5 x upper limit of normal (ULN)
• Prothrombin time (PT), partial thromboplastin time (PTT) =\< 1.5 x ULN
• Total bilirubin =\< 1.5 x ULN
• Alanine transaminase (ALT) and aspartate aminotransferase (AST) \< 1.5 x ULN (\< 5 x ULN if patient has liver metastasis)
• Patient will have a tumor suitable for fine needle aspirates (FNA) or core biopsy for research purposes (2 or more FNAs if core is not feasible)
• Able to swallow oral medications
• Patient must have performance status =\< 2 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Measurable disease by RECIST or evaluable disease (e.g., bone metastasis, or lesions which do not fulfill RECIST criteria for metastatic disease)
• ALK-positive NSCLC patients with asymptomatic central nervous system (CNS) metastases who are neurologically stable or have not required increasing doses of steroids within the 2 week prior to study entry to manage CNS symptoms
• Non-ALK-positive NSCLC patients with CNS metastasis should have completed a course of therapy would be eligible for the study provided they are clinically stable for 1 month prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis (2) off steroids

You may not qualify if:

• Patients who have received prior everolimus or 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 (i.e. affecting activities of daily living or requiring therapeutic intervention)
• Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks including chemotherapy, radiation therapy, antibody based therapy, etc.
• Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus)
• Patients with known hypersensitivity to any of the excipients of ceritinib (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate)
• Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
• Uncontrolled diabetes mellitus as defined by hemoglobin A1c (HbA1c) \> 8% despite adequate therapy; patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary
• 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 mmHg and/or diastolic blood pressure (DBP) \>= 100 mmHg, 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 interval (QTc) \> 450 msec using Fridericia correction on the screening electrocardiogram (ECG)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

ceritinib; Everolimus

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• George R Blumenschein

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2014
• First Posted: December 22, 2014
• Study Start: June 22, 2016
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 20, 2026

Record last verified: 2026-05

Locations

US (1)