Clinical trial NCT02580045: Pharmacokinetics of Systemic Anti-Cancer Therapies in the Cerebrospinal Fluid (CSF) of Patients With Advanced Cancer
Official title: CSF Pharmacokinetics of Systemic Anti-Cancer Therapies in Patients With Advanced Cancer
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Metastatic Cancer Patients on an Anti-cancer Therapy
Advanced Cancer
Brain Metastasis
Keywords: metastatic cancer
lumbar puncture
advanced cancer
brain metastases
chemotherapy
endocrine therapy
HER2 targeted therapy
immune therapy
anti-cancer therapy
blood brain barrier
pharmacokinetics
Duke University
brain metastasis
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2015-10-20
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
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.

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The concentration of drug metabolites of systemic anti-cancer therapies in the cerebrospinal fluid
timeFrame: up to 3 weeks
measure: Ratio of serum to CSF concentration of systemic anti-cancer therapies as measured by concentration of drug metabolites in serum and in CSF
timeFrame: up to 3 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Kimberly L Blackwell, MD
role: PRINCIPAL_INVESTIGATOR
References: