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

Advanced Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02580045
• Other study ID #: Pro00062142
• Status: Terminated
• Phase: N/A
• First received: October 7, 2015
• Last updated: February 26, 2018
• Start date: April 1, 2016
• Est. completion date: February 22, 2018

Study information

• Verified date: February 2018
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: February 22, 2018
• Est. primary completion date: February 22, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Cancer
• Brain Metastasis
• Brain Neoplasms
• Metastatic Cancer Patients on an Anti-cancer Therapy
• Neoplasm Metastasis
• Neoplasms

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Duke University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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