Last updated on August 2018

Phase I/Ib Dose Escalation & Biomarker Study of Ceritinib (LDK378) + Everolimus for Locally Advanced or Metastatic Solid Tumors With an Expansion in Non-Small Cell Lung Cancer (NSCLC) Characterized by Abnormalities in Anaplastic Lymphoma Kinase (ALK) Expression


Brief description of study

The goal of this clinical research study is to find the highest tolerable dose of ceritinib (LDK378) and everolimus that can be given to patients with NSCLC or head and neck cancer. The safety of the drug combination will also be tested.

This is an investigational study. LDK 378 is FDA approved and commercially available for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic lung cancer (NSCLC) who have progressed on or intolerant to crizotinib.

Everolimus is also FDA approved or commercially available for the treatment of advanced hormone receptor-positive, HER2-negative breast cancer, advanced neuroendocrine tumors of pancreatic origin (PNET), advanced renal cell carcinoma (RCC), renal angiomyolipoma and tuberous sclerosis complex (TSC), and subependymal giant cell astrocytoma (SEGA) with Tuberous Sclerosis Complex (TSC).

The combination of the drugs is being used for research purposes only.

Up to 66 participants will be enrolled in this study. All will take part at MD Anderson.

Detailed Study Description

Study Groups and Study Drug Administration:

If you are found to be eligible to part in this study, the dose of LDK378 you receive will depend on when you join this study. The first group of participants will receive the lowest dose level of LDK 378 and everolimus. Each new group will receive either higher dose of LDK 378 or a higher dose of everolimus than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of LDK 378 and everolimus is found.

Once the high tolerable dose is found, up to 30 participants will receive the drug at this dose level.

You will take 2 to 4 capsules (depending on the dose) of LDK 378 by mouth 1 time each day for each 28-day study cycle.

LDK 378 should be taken in the morning right after (within 30 minutes) a low-fat meal (about 1.5 to 9 grams of fat [no more than 15 grams] and about 100 to 330 total calories [no more than 500 total calories]). You should swallow the capsule whole with a cup of water (about 8 ounces) over as short a time as possible (not slower than 1 capsule every 2 minutes). Do not chew or open the capsules.

If you vomit or miss a dose, do not take another dose to make it up. That day's dose should be skipped, and you should take your next dose on the following day.

You will take 1 or 2 capsules of everolimus (depending on the dose) tablets by mouth 1 time each day for each 28-day cycle. Everolimus should be taken at about the same time every day with a glass of water, either consistently with or without food

Study Visits:

On Day 1 of Cycle 1:

  • You will have a physical exam, including a check of your blood oxygen level.
  • Blood (about 2 teaspoons) will be drawn for routine tests and to check your cholesterol levels. You must fast for at least 12 hours before the draw.
  • Blood (about 2 teaspoons at each draw) will be drawn for pharmacokinetic (PK) and biomarker testing before your dose of LDK378 and then 6 more times over the next 24 hours after the dose. PK testing measures the amount of study drug in the body at different time points.

On Days 8, 15, and 21 of Cycle 1:

  • You will have a physical exam.
  • Blood (about 2 teaspoons) will be drawn for routine tests and to check your cholesterol levels. You must fast for at least 12 hours before the draw.
  • On Days 15 and 21 only, blood (about 2 teaspoons) will be drawn for PK and biomarker testing.

On Day 1 of Cycle 2:

  • You will have a physical exam, including a check of your blood oxygen level.
  • Blood (about 2 teaspoons) will be drawn for routine tests and to check your cholesterol levels. You must fast for at least 12 hours before the draw.
  • You will have an EKG before you take the study drug.
  • Blood (about 2 teaspoons at each draw) will be drawn for PK testing before and 6 more times between 1-24 hours after your dose of study drugs.
  • If you can become pregnant, blood (about teaspoon) or urine will be collected for a pregnancy test.

On Day 1 of Cycle 3:

  • You will have a physical exam, including a check of your blood oxygen level.
  • Blood (about 2 teaspoons) will be drawn for routine tests and to check your cholesterol levels. You must fast for at least 12 hours before the draw.
  • You will have an EKG before you take the study drug.
  • Blood (about 2 teaspoons) will be drawn for PK and biomarker testing.
  • If you can become pregnant, blood (about teaspoon) or urine will be collected for a pregnancy test.

On Day 1 of Cycles 3 and every other cycle after that (Cycles 5, 7 and so on), you will have a CT scan or MRI of your chest, abdomen, and brain to check the status of the disease.

On Day 1 of Cycles 4 and beyond:

  • You will have a physical exam, including a check of your blood oxygen level.
  • Blood (about 2 teaspoons) will be drawn for routine tests and to check your cholesterol levels. You must fast for at least 12 hours before the draw.
  • You will have an EKG before you take the study drug.
  • If you can become pregnant, blood (about teaspoon) or urine will be collected for a pregnancy test.

If at any time the disease appears to get worse while you are on study, you will have an FNA or core biopsy for biomarker testing.

If the doctor thinks it is needed, you will have extra EKGs.

Length of Study:

You may continue taking the study drugs as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation in this study will be over after the end-of-study visit.

End-of-Study Visit:

Within 28 days of your last dose of study drugs:

  • You will have a physical exam, including a check of your blood oxygen level.
  • Blood (about 2 teaspoons) will be drawn for routine tests and to check your cholesterol levels. You must fast for at least 12 hours before the draw.
  • Blood (about 2 teaspoons) will be drawn for PK and biomarker testing.
  • If you can become pregnant, blood (about teaspoon) or urine will be collected for a pregnancy test.

Clinical Study Identifier: NCT02321501

Contact Investigators or Research Sites near you

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George Blumenschein, MD

University of Texas MD Anderson Cancer Center
Houston, TX United States
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