Clinical trial NCT04994977: Intra-Arterial Chemotherapy for Newly Diagnosed, Residual, or Recurrent Atypical Choroid Plexus Papilloma and Choroid Plexus Carcinoma Prior to Second-Look Surgery
Official title: Intra-Arterial (IA) Chemotherapy for Newly Diagnosed, Residual, or Recurrent Atypical Choroid Plexus Papilloma (ACPP) and Choroid Plexus Carcinoma (CPC) Prior to Second-Look Surgery
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Atypical Choroid Plexus Papilloma
Choroid Plexus Carcinoma
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
First posted: 2021-08-06
Enrollment: 1
Sex: ALL
Minimum age (years): 0
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will test the safety and efficacy of intra-arterial chemotherapy in subjects with newly diagnosed, residual, or recurrent atypical choroid plexus papilloma and choroid plexus carcinoma prior to a second surgery.

It is believed that intra-arterial chemotherapy will be safe and feasible for this population and will result in decreased tumor size, which may further improve the goals of a second-look surgery.

Detailed description: The intent of this study is to determine if intra-arterial chemotherapy is a safe and effective option for subjects with atypical choroid plexus papilloma and choroid plexus carcinoma prior to receiving second-look surgery. Angiography occurs when a catheter is inserted through the subjects vasculature to the major vessels that supply cerebral circulation. Subjects on this trial will undergo a a cerebral angiogram to determine the ideal arteries to use for drug infusion. Once identified, chemotherapy will be delivered through the catheter directly to the site of tumor.

Eligibility criteria: Inclusion Criteria:

1. Subjects with a histologically confirmed diagnosis of ACPP or CPC that is newly diagnosed, residual or recurrent.
2. Subjects must have a Karnofsky or Lansky Performance Score ≥ 60 % assessed within two weeks prior to enrollment. Karnofsky is used for patients ≥ 16 years and Lansky for those \< 16.
3. Subjects must have normal organ and marrow function documented within 14 days of enrollment and within 7 days of the start of treatment as noted below:

   1. Absolute neutrophil count ≥ 1,000/μL
   2. Platelets ≥ 100,000/μL (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to enrollment)
   3. Hemoglobin ≥ 8 g/dL (may receive PRBC transfusions)
   4. Total bilirubin \< 1.5 times upper limit of normal for age
   5. AST (SGOT)/ALT(SGPT) \< 2.5 X institutional upper limit of normal for age
   6. Creatinine clearance or radioisotope GFR ≥ 70 ml/min/1.73m2 or a serum creatinine WNL for age as determined using the Schwartz formula.36
   7. Sodium, Potassium, Calcium and Magnesium \< 1.5x institutional ULN
   8. Albumin ≥ 3 g/dL
4. Subjects who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment.
5. Subjects with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment.
6. If the subject has any of the following therapies, must be at least:

   * 4 weeks post-focal RT (radiation therapy), 3 months post-CSI (craniospinal irradiation)
   * 4 weeks post-myelosuppressive chemotherapy (if post-nitrosoureas, must have 6 weeks therapy)
   * 4 weeks post-monoclonal antibodies
   * 1 week post-targeted therapy
7. If subject has received any previous treatment, all treatment related toxicities should have recovered to \< grade 2
8. Subject or parent must sign a written informed consent document according to institutional guidelines.

Exclusion Criteria:

1. Females who are pregnant or lactating.
2. Subjects with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) likely to interfere with the study procedures or results.
3. Subjects who are receiving any other anticancer or investigational agents.
4. Subjects with uncontrolled seizures.
5. Subjects receiving enzyme inducing anticonvulsants.
6. Subjects with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) including heart failure that meets New York Heart Association (NYHA) class II or above.
7. Subjects who have had an allogenic bone marrow transplant \< 6 months prior to enrollment or an autologous bone marrow/stem cell transplant \< 3 months prior to enrollment.
8. Subjects with multifocal disease or disease that has been disseminated will not be eligible for this study. They will undergo systemic chemotherapy and their disease will be further evaluated prior to be eligible for 2nd look surgery.
9. This study will only enroll subjects with ACPP or CPC and will not enroll subjects with choroid plexus papilloma (CPP). ACPP or CPC subjects with symptomatic hydrocephalus will not be eligible for this study. These subjects will have to be treated for their hydrocephalus and be re-evaluated according to our eligibility criteria in order to be enrolled.

Primary outcomes:
measure: Safety of intra-arterial chemotherapy in subjects with ACPP and CPC, measured by the number of serious adverse events that are reported as at least possible related to the intervention that occur in subjects on the trial
timeFrame: Through study completion, a little over a year for each subject
Secondary outcomes:
measure: The number of successful angiography procedures, determined by examination of vasculature and assessment of catheter placement
timeFrame: On Day 1 of the trial for each subject
measure: The number of patients with a tumor volume reduction response, determined by MRI assessments
timeFrame: Between 4-6 weeks after intra-arterial chemotherapy
measure: The proportion of patients with a tumor volume reduction response, determined by MRI assessments
timeFrame: Between 4-6 weeks after intra-arterial chemotherapy
measure: The number of patients with a tumor vascularity reduction response, determined by MRI assessments
timeFrame: Between 4-6 weeks after intra-arterial chemotherapy
measure: The proportion of patients with a tumor vascularity reduction response, determined by MRI assessments
timeFrame: Between 4-6 weeks after intra-arterial chemotherapy
measure: The success of second look surgery determined by measuring the extent of tumor resection
timeFrame: Around 7 weeks after intra-arterial chemotherapy, during second look surgery
measure: The success of second look surgery determined by amount of blood loss
timeFrame: Around 7 weeks after intra-arterial chemotherapy, during second look surgery
measure: The success of second look surgery determined by percent of blood loss
timeFrame: Around 7 weeks after intra-arterial chemotherapy, during second look surgery
Other outcomes:
measure: Extent of pathology correlation to tumor vascularity and tumor viability
timeFrame: Around 7 weeks after intra-arterial chemotherapy
Locations:
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Mark Souweidane, M.D.
role: PRINCIPAL_INVESTIGATOR
References: