Pharmacokinetics of Systemic Anti-Cancer Therapies in the Cerebrospinal Fluid (CSF) of Patients With Advanced Cancer

CSF Pharmacokinetics of Systemic Anti-Cancer Therapies in Patients With Advanced Cancer

This clinical trial is being done to learn more about how different types of cancer treatments affect cancer cells when they spread to the brain. Many cancer treatments are not able to make their way into the brain or into spinal fluid of the central nervous system. This is because they cannot cross what is called the "blood-brain barrier" or "BBB". The BBB is like a protective shield that only allows certain materials pass through to reach the brain but not others. This study is being initiated to help researchers learn more about what types of cancer treatments make it through the BBB to attack cancer cells within the brain, and what treatments do not make it through the BBB. Learning more about this may help future researchers develop more effective cancer drugs that better fight cancer cells that have spread to the brain.

Study Overview

• Status: Terminated
• Conditions: Advanced Cancer; Brain Metastasis; Metastatic Cancer Patients on an Anti-cancer Therapy

Detailed Description

Very little is known about the penetration of systemic therapies through the normal blood brain barrier and the ways in which a brain metastasis or radiation would impact the permeability of the blood brain barrier. This study would be one of the first to examine the concentrations of systemic cancer therapies in the cerebrospinal fluid (CSF) with matched serum samples. Additionally, the concentration of these therapies in brain metastasis surgical specimens would be of particular interest to correlate with serum and CSF levels, length of time on therapy, and latency to developing brain metastases in future studies.

As participants in this study, patients scheduled for a lumbar puncture per their standard of care treatment will be subject to a withdrawal of 15cc's of cerebrospinal fluid for pharmacokinetic analysis. They will also have a blood draw of 5mL within 2 hours of the lumbar puncture for serum pharmacokinetics. If the patient is eligible for and elects to proceed with surgical resection of a brain metastasis, optional CSF and serum samples would be drawn at the time of resection.

• Study Type: Observational
• Enrollment (Actual): 3

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Metastatic or advanced cancer patients on systemic anti-cancer therapy including chemotherapy, endocrine therapy, HER2-targeted therapy, and immune therapy.

Description

Inclusion Criteria:

1. Metastatic cancer patients on systemic anti-cancer therapy (chemotherapy, endocrine therapy, HER2 targeted therapy, immune therapy).
2. Patients must be able to have a lumbar puncture within 2 half-lives of the last dose of systemic therapy.
3. Patients undergoing an LP for any reason with known advanced cancer on systemic anti-cancer therapy are eligible.
4. Patients with new or previously treated brain metastases are eligible.
5. Patients may have received prior stereotactic radiosurgery to the brain and/or whole brain radiation.
6. No limitations on prior systemic or intrathecal therapies.
7. There are no restrictions on systemic therapy at enrollment.
8. Laboratory criteria: normal renal function: creatinine < 1.5 x upper limit of normal (ULN)), liver function: bilirubin < 1.5 x ULN, transaminases < 2 x ULN, except in known hepatic disease, wherein may be < 5 x ULN, and blood counts: WBC ≥ 2.0, Neutrophils ≥1500, platelets ≥100,000, Hemoglobin ≥ 10.
9. Age > 18 years
10. Patients must have the ability to give informed consent.
11. Patients must have a signed informed consent form prior to enrollment on study.

Exclusion Criteria:

1. No history of lumbar surgery or other pre-existing spinal conditions that would preclude a safe, reliable lumbar puncture.
2. Patients should have no significant psychiatric illness or medical illness that would preclude the ability to comply with the protocol.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The concentration of drug metabolites of systemic anti-cancer therapies in the cerebrospinal fluid	CSF pharmacokinetics of systemic anti-cancer therapies, as measured by the concentration of their metabolites in the cerebrospinal fluid, will be obtained via lumbar puncture. The lumbar puncture will take place within 2 half-lives of the last dose of systemic therapy. Because a wide variety of anti-cancer therapies will be studied in this trial, there is significant variability in the half-lives of these therapies. Some will take place 2-24 hours after the last dose of systemic therapy. Some will take place 1-6 days after the last dose of systemic therapy. Some will take place 1-3 weeks after the last dose of systemic therapy. The time of the lumbar puncture procedure will depend greatly on the identity of the systemic therapy with which the subject is being treated. In patients undergoing surgical resection of a brain metastasis, an additional CSF sample is optional.	up to 3 weeks
Ratio of serum to CSF concentration of systemic anti-cancer therapies as measured by concentration of drug metabolites in serum and in CSF	CSF and serum pharmacokinetics of systemic anti-cancer therapies, as measured by the concentration of their metabolites, will be obtained via lumbar puncture and blood draw, respectively. The lumbar puncture and blood draw will take place together within 2 half-lives of the last dose of systemic therapy. Because a wide variety of anti-cancer therapies will be studied in this trial, there is significant variability in the half-lives of these therapies. Some will take place 2-24 hours after the last dose of systemic therapy. Some will take place 1-6 days after the last dose. Some will take place 1-3 weeks after the last dose. The time of the lumbar puncture procedure will depend greatly on the identity of the systemic therapy with which the subject is being treated. In patients undergoing surgical resection of a brain metastasis, an additional matched CSF and serum sample is optional.	up to 3 weeks

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Kimberly L Blackwell, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): February 22, 2018
• Study Completion (Actual): February 22, 2018

Study Registration Dates

• First Submitted: October 7, 2015
• First Submitted That Met QC Criteria: October 16, 2015
• First Posted (Estimate): October 20, 2015

Study Record Updates

• Last Update Posted (Actual): February 28, 2018
• Last Update Submitted That Met QC Criteria: February 26, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: chemotherapy; pharmacokinetics; blood brain barrier; metastatic cancer; advanced cancer; brain metastases; brain metastasis; immune therapy; lumbar puncture; Duke University; endocrine therapy; HER2 targeted therapy; anti-cancer therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: Pro00062142