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Nervous System Neoplasms

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Palbociclib

Benzocaine

Protein Kinase Inhibitors

Enzyme Inhibitors

Tannic Acid

Description Patients who fulfill eligibility criteria will be entered into the trial to receive Palbociclib

After the screening procedures confirm participation in the research study:

* Palbociclib- Fixed Dose, daily for 21 days per cycle.
* The participant will be requested to maintain a medication diary of each dose of medication. The medication diary will be returned to clinic staff at the end of each cycle.

Priscilla Brastianos, MD

Eudocia K. Lee, MD

Eudocia Lee, MD

This research study is studying palbociclib as a possible treatment for recurrent brain metastases.

- Pfizer, a pharmaceutical company, is supporting this research study by providing the study drug as well as funding for research activities

* This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.
* This is a study designed to evaluate the efficacy and safety of palbociclib in recurrent brain metastases. Palbociclib is being studied for use in the treatment of a broad range of cancers. This type of drug inhibits cell growth in the cells called cyclin-dependent kinases which promote tumor cell proliferation.
* The FDA (the U.S. Food and Drug Administration) has not approved palbociclib for participants specific disease but it has been approved for other uses

Palbociclib In Progressive Brain Metastases

A Phase 2 Study of Palbociclib in Progressive Brain Metastases Harboring Alterations in the CDK Pathway

Simon two-stage design comparing the proportion of intracranial responders (as defined by CR, PR or SD) under a null hypothesis response rate of 10% against an alternative of 30%.

Kaplan-Meier estimates of overall survival will be presented with 90% confidence intervals estimated using log(-log(survival)) methodology

Pfizer

Massachusetts General Hospital

Principal Investigator

Neoplasms, Second Primary

Patients will be initially administered 8 Gy RT (level). The dose at each level will be increase by 2 Gy up to level 4. If ≥ 2 of the patients in a dose cohort encounter a DLT, then that dose level will be declared the maximum administered dose. An additional 3 patients will then be entered at the previous dose level and provided no more than one patient experiences a DLT, that level will be declared the maximum tolerated dose (MTD). Up to 6 more patients can be treated at the given dose level while awaiting the results of 6 months of follow-up.

Hypofractionated stereotactic radiotherapy

Caroline Chung, MD

Brain metastases occur in 20% to 40% of all patients with cancer , with an incidence 10 times higher than that of primary malignant brain tumors. Patients with brain metastases have a poor prognosis with a median survival of 1-2 months with corticosteroids and 5-7 months with whole brain radiotherapy (WBRT). Local control achieved with WBRT in patients with otherwise controlled systemic disease remains at issue. A single high dose of radiation delivered with high precision to the target lesion (Stereotactic radiosurgery (SRS)), is considered standard care in salvage of recurrent lesions after WBRT. SRS can destroy tumour with very little damage to surrounding tissue. Research suggests that delivering radiotherapy in a number of smaller doses is more beneficial than receiving all of the radiotherapy in a single dose. Brain metastases are well suited for SRS as they are often small, radiographically well-circumscribed, pseudospherical tumors that are noninfiltrative.

With increasing volume of tumor, the dose of radiosurgery that can be safely delivered to recurrent oligo-metastases in the brain must be reduced. However, reducing the dose of radiosurgery also compromises local control. There is mounting evidence of a local control benefit to a hypofractionated approach in radiation delivery for brain metastases compared with single fraction radiosurgery. Here we propose a novel therapeutic strategy that builds on this concept whereby time between each delivered fraction will enable us to measure and adapt to response, with the objective of reducing irradiated volumes and improving outcomes. In general, the treatment of malignant tumors benefits from fractionation of the dose due to a number of radiobiological properties (redistribution, reoxygenation, repair) that distinguish, and select against, malignant lesions in the fractionation process. Hypofractionated stereotactic radiotherapy (HSRT) is a method of delivering a highly conformal dose distribution in a few treatment sessions using a relocatable stereotactic frame. HSRT may be an attractive alternative to SRS because it may 1) improve patient comfort by removing the invasive nature of SRS frames, 2) confer a radiobiologic advantage over single fraction treatment.

Perfexion Brain Metastasis

Hypofractionated Stereotactic Radiotherapy (HF-SRT) for Large-Volume Brain Metastases

Princess Margaret Hospital, Canada

University Health Network, Toronto

Single intravenous administration of 18F fluciclovine for PET Scan

18F fluciclovine injection, 185 MegaBecquerel (MBq) (5 Millicurie (mCi)) ± 20%, delivered as an intravenous bolus

18F fluciclovine

Eugene Teoh, MD

Rupesh Kotecha, MD

An Open-label, Single-arm, Single-dose, Prospective, Multicenter Phase 2b Study to Establish Image Interpretation Criteria for 18F-Fluciclovine Positron Emission Tomography (PET) in Detecting Recurrent Brain Metastases After Radiation Therapy

Positron Emission Tomography (PET) Imaging study

Study to Establish Image Interpretation Criteria for 18F Fluciclovine PET in Detecting Recurrent Brain Metastases (PURSUE)

Sensitivity is calculated as % of participants with positive histopathology who are classified as positive on their 18F fluciclovine PET (i.e. true positive). Each participant had one lesion, therefore results are representative of both subject and lesion level sensitivity.

Three readers evaluated the PET scans to classify 18F fluciclovine uptake in study lesions according to 4 incremental categories: absent, mild, moderate or marked. Three different thresholds of 18F fluciclovine uptake were then applied to calculate the sensitivity: Mild or Higher Uptake, Moderate or Higher Uptake, Marked Uptake. As an example, for calculating sensitivity based on the threshold of Mild or Higher Uptake, all participants with positive histopathology, classified by a reader as having mild, moderate or marked 18F fluciclovine uptake, would be categorized as true positive. This calculation was then repeated on the other two threshold categories, to produce sensitivities at different thresholds.

Specificity is calculated as the % of participants with negative histopathology who are classified as negative on their 18F fluciclovine PET (i.e. true negative). Each participant had 1 lesion, therefore results are representative of both subject and lesion level specificity. 3 readers evaluated the PET scans to classify 18F fluciclovine uptake in study lesions according to 4 incremental categories: absent, mild, moderate or marked. 3 different thresholds of uptake were then applied to calculate the specificity: Mild or Higher Uptake, Moderate or Higher Uptake, Marked Uptake. Example, for calculating specificity based on the threshold of Moderate or Higher Uptake, all participants with negative histopath, classified by a reader as having absent or mild uptake (i.e. not classified by a reader as having moderate or marked uptake), would be categorized as true negative. This calculation was repeated on the other 2 threshold categories, to produce specificities at different thresholds

Sensitivity calculated as %participants with positive histopath and positive on PET (i.e. true positive). Each participant had 1 lesion, results represent both subject and lesion level sensitivity. Sensitivity is calculated using positive PET classified by quantitative and dynamic measures. Quantitative measure is based on lesion standardized uptake value (SUV). Receiver Operating Characteristic (ROC) analysis of all participant lesion SUV was performed. ROC analyses was performed to select a SUV threshold for calculating sensitivity. Sensitivity calculation: participants with positive histopath and SUV = or \> threshold are positive on scan. Dynamic measure: 3 readers evaluated PET scans to classify uptake pattern based on 4 categories: Type 0, Type I, Type II, Type III. Sensitivity is calculated for each type of uptake pattern (example: calculating sensitivity based on Type I pattern, participants with positive histopath, classified as Type I, would be categorized as true positive).

Specificity is calculated as %participants with negative histopath and negative on PET (i.e. true negative). Each participant had 1 lesion, results represent both subject and lesion level specificity. Specificity is calculated using negative PET classified by quantitative and dynamic measures. Quantitative measure is based on lesion standardized uptake value (SUV). Receiver Operating Characteristic (ROC) analysis of all participant lesion SUV was performed. ROC analyses was performed to select a SUV threshold for calculating sensitivity. Specificity calculation: participants with negative histopath, SUV \< threshold are negative on scan. Dynamic measure: 3 readers evaluated PET scans to classify uptake pattern based on 4 categories: Type 0, Type I, Type II, Type III. Specificity is calculated for each type of uptake pattern (example, calculating specificity based on Type I pattern, participants with negative histopath, classified as Type I, would be categorized as true negative)

Safety will be assessed from data on the occurrence of one or more treatment-emergent Adverse Events from the time of intravenous administration of 18F fluciclovine until 1 day post-18F-fluciclovine administration.

Precision For Medicine

Blue Earth Diagnostics

Subjects who have been dosed with 18F-Fluciclovine, have an evaluable on-study PET scan, and an evaluable central histopathology report from the sample obtained from the SoC craniotomy.

18F-Fluciclovine Injection

Single intravenous administration of 18F fluciclovine for PET Scan

18F fluciclovine: 18F fluciclovine injection, 185 MBq (5 mCi) ± 20%, delivered as an intravenous bolus

Patients

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Chief Medical Officer

Mild or Higher Uptake = Positive : Central Reader 1

Mild or Higher Uptake = Positive : Central Reader 2

Mild or Higher Uptake = Positive : Central Reader 3

Moderate or Higher Uptake = Positive : Central Reader 1

Moderate or Higher Uptake = Positive : Central Reader 2

Moderate or Higher Uptake = Positive : Central Reader 3

Marked Uptake = Positive : Central Reader 1

Marked Uptake = Positive : Central Reader 2

Marked Uptake = Positive : Central Reader 3

Subjects who have been dosed with 18F-Fluciclovine, have an evaluable on-study PET scan, and positive histopathology.

Sensitivity analysis (%) based on 10 subjects with positive lesions per standard of truth (central histopathological analysis).

Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds

Subjects who have been dosed with 18F-Fluciclovine, have an evaluable on-study PET scan, and negative histopathology.

Specificity analysis (%) based on 13 subjects with negative lesions per standard of truth (central histopathological analysis).

Specificity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds

Quantitative SUV ≥ 4.8 = Positive : Central Reader 1

Quantitative SUV ≥ 4.8 = Positive : Central Reader 2

Quantitative SUV ≥ 4.8 = Positive : Central Reader 3

Dynamic Type 0: Central Reader 1

Dynamic Type 0 : Central Reader 2

Dynamic Type 0 : Central Reader 3

Dynamic Type I: Central Reader 1

Dynamic Type I: Central Reader 2

Dynamic Type I: Central Reader 3

Dynamic Type II: Central Reader 1

Dynamic Type II: Central Reader 2

Dynamic Type II: Central Reader 3

Dynamic Type III: Central Reader 1

Dynamic Type III: Central Reader 2

Dynamic Type III: Central Reader 3

Subjects who have been dosed with 18F-Fluciclovine, have an evaluable on-study PET scan, and positive histopathology

Sensitivity analysis (%) based on 10 subjects with positive lesions per standard of truth.

Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases Based on Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake

SUV ≥ 4.8 : Central Reader 1

SUV ≥ 4.8 : Central Reader 2

SUV ≥ 4.8 : Central Reader 3

Dynamic Type 0 : Central Reader 1

Dynamic Type I : Central Reader 1

Dynamic Type I : Central Reader 2

Dynamic Type I : Central Reader 3

Dynamic Type II : Central Reader 1

Dynamic Type II : Central Reader 2

Dynamic Type II : Central Reader 3

Dynamic Type III : Central Reader 1

Dynamic Type III : Central Reader 2

Dynamic Type III : Central Reader 3

Specificity of 18F fluciclovine PET for detecting recurrent brain metastases based on quantitative and dynamic measures of lesion 18F fluciclovine uptake

Specificity of Different Thresholds of Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake.

Subjects reporting at least 1 TEAE

Nervous System Disorders (Headache)

Safety will be assessed from data on the occurrence of one or more treatment-emergent Adverse Events from the time of intravenous administration of 18F fluciclovine until 2 days post-18F-fluciclovine administration.

Treatment-emergent Adverse Events

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Skin and Connective Tissue Diseases

Lung Neoplasms

Breast Neoplasms

Disease Attributes

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Patients receive Cabazitaxel 25 mg/m2 i.v. infusion. This trial is a single arm trial.

Cabazitaxel 25 mg/m2 i.v. infusion (infusion time about 1h) on D1 of each 21-day cycle. Continuation of treatment until progression of brain metastases or unacceptable toxicity.

Cabazitaxel

Frank Kullmann, Prof. Dr.

Patients suffering from histologically or cytologically confirmed stage IV lung or breast cancer with progressive or recurrent brain metastases after prior external beam radiotherapy will receive treatment with cabazitaxel until progression of brain metastases (BM) or unacceptable toxicity.

Cabazitaxel is a new taxane compound that exhibited a broad spectrum of in vivo antitumor activity, not only in docetaxel - sensitive tumor models, but also in tumors models in which docetaxel was poorly or not active. In contrast to other taxanes, cabazitaxel has the ability to cross the blood-brain-barrier. Marked antitumor activity was obtained in nude mice bearing intracranial glioblastomas. Consequently, there is a good rationale to investigate cabazitaxel in patients with breast or lung cancer and recurrent or progressive brain metastases.

The primary object of the study is to measure objective tumor response of brain metastases for patients with breast or lung cancer and recurrent or progressive brain metastases.

A Study of Cabazitaxel for Patients With Breast or Lung Cancer and Recurrent or Progressive Brain Metastases - Cabazitaxel for Brain Metastases (CaBaMet)

A Phase II Study of Cabazitaxel for Patients With Breast or Lung Cancer and Recurrent or Progressive Brain Metastases - Cabazitaxel for Brain Metastases (CaBaMet)

Objective tumor response of brain metastases (Complete response (CR) or partial response (PR) or at least a minor response (MR; 25-50% reduction) according to WHO criteria1,2 and Iwamoto3 confirmed by magnetic resonance imaging (MRI))

Efficacy measure, assessed with EORTC QLQ-C30 and additional module BN20 questionnaire

ClinAssess GmbH

Sanofi

AIO-Studien-gGmbH

Patients will undergo craniotomy and patients in the treatment arm will undergo implantation of Cesium 131 brachytherapy in coordination with the radiation oncologist.

Craniotomy

Cesium-131 brachytherapy

Nelson Moss, MD

Brandon Imber, MD

Adam Robin, MD

The purpose of this study is to see if Cs-131 brachytherapy is effective in people with recurrent brain cancer who are scheduled to have brain surgery for removal of their tumor(s). The researchers would like to see whether Cs-131 prevents brain tumors from growing back after surgery.The researchers will compare Cs-131 brachytherapy (which occurs during brain surgery) with the usual approach of brain surgery without brachytherapy. The researchers will compare both the effectiveness and safety of the two approaches.

Prospective randomized phase II multicenter trial.

Patient will be blinded to their treatment until postoperatively.

Intracavitary Carrier-embedded Cs131 Brachytherapy for Recurrent Brain Metastases: a Randomized Phase II Study

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

With a contrast enhanced brain MRI scan. Treatment response will be determined based on the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria.

Physical examination including wound examination will be performed, and wound complications (including dehiscence, superficial/deep infection, CSF leak) will be recorded by the evaluating clinicians.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Palbociclib In Progressive Brain Metastases	NCT02896335	Metastatic Mali...	Palbociclib	18 Years -	Massachusetts General Hospital
Perfexion Brain Metastasis	NCT00805103	Brain Metastase...	Hypofractionate...	18 Years -	University Health Network, Toronto
Study to Establish Image Interpretation Criteria for 18F Fluciclovine PET in Detecting Recurrent Brain Metastases (PURSUE)	NCT04410367	Brain Metastase...	18F fluciclovin...	18 Years -	Blue Earth Diagnostics
A Study of Cabazitaxel for Patients With Breast or Lung Cancer and Recurrent or Progressive Brain Metastases - Cabazitaxel for Brain Metastases (CaBaMet)	NCT02166658	Breast Cancer Lung Cancer Recurrent Brain... Progressive Bra...	Cabazitaxel	18 Years -	AIO-Studien-gGmbH
Intracavitary Carrier-embedded Cs131 Brachytherapy for Recurrent Brain Metastases: a Randomized Phase II Study	NCT04690348	Recurrent Brain...	Craniotomy Cesium-131 brac...	18 Years -	Memorial Sloan Kettering Cancer Center
LITT and Pembrolizumab in Recurrent Brain Metastasis	NCT04187872	Melanoma Non-small Cell ... Renal Cell Carc... Small-cell Lung... Head and Neck S... Classical Hodgk... Primary Mediast... Urothelial Carc... Microsatellite ... Gastric Cancer Esophageal Canc... Cervical Cancer Hepatocellular ... Merkel Cell Car... Brain Metastase...	LITT + Pembroli...	18 Years - 100 Years	University of Florida
Study to Establish Image Interpretation Criteria for 18F Fluciclovine PET in Detecting Recurrent Brain Metastases (PURSUE)	NCT04410367	Brain Metastase...	18F fluciclovin...	18 Years -	Blue Earth Diagnostics
Perfexion Brain Metastasis	NCT00805103	Brain Metastase...	Hypofractionate...	18 Years -	University Health Network, Toronto
Meclofenamate in Subjects With Recurrent or Progressive Brain Metastasis From Solid Tumor Primary	NCT02429570	Recurrent Brain... Progressive Bra...	Meclofenamate	18 Years - 80 Years	Memorial Sloan Kettering Cancer Center
Study to Establish the Diagnostic Performance of 18F Fluciclovine PET in Detecting Recurrent Brain Metastases	NCT04410133	Brain Metastase...	18F fluciclovin...	18 Years -	Blue Earth Diagnostics

Spots Global Cancer Trial Database for recurrent brain metastases