Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Nervous System Diseases

Breast Neoplasms

Neoplasm Metastasis

Meningeal Carcinomatosis

Neoplasms, Second Primary

Brain Neoplasms

Carcinoma

Breast Diseases

Skin Diseases

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Meningeal Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Micronutrients

Hematinics

Vitamins

Paclitaxel

Capecitabine

Methotrexate

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Folinic Acid

Folate

Vitamin B9

One of the protocol specified Physician's Best Choice therapies, assigned by the Investigator prior to randomization: capecitabine or eribulin or high-dose intravenous (IV) methotrexate.

ANG1005

Active Comparator: one of 3 pre-determined choices of therapies: capecitabine or eribulin or high-dose IV methotrexate.

Physician's Best Choice

John Huss

This is an open-label Phase 3 study to see if ANG1005 can prolong survival compared to a Physician Best Choice control in HER2-negative breast cancer patients with newly diagnosed leptomeningeal disease and previously treated brain metastases.

1:1 randomization to experimental arm and comparator arm

ANG1005 in Leptomeningeal Disease From Breast Cancer

A Randomized Open-Label, Multi-Center Pivotal Study of ANG1005 Compared With Physician's Best Choice in HER2-Negative Breast Cancer Patients With Newly Diagnosed Leptomeningeal Carcinomatosis and Previously Treated Brain Metastases (ANGLeD)

Angiochem Inc

Recurrence

Meningitis

Neuroinflammatory Diseases

Pharmaceutical Solutions

RTA 744 injection administered intravenously for a maximum of 18 cycles (54 weeks). Dose escalation based on four dose levels and occurance of dose limiting toxicity (DLT).

Aqueous solution of RTA 744 is packaged in 5 ml vials - 1 mg/ ml. The drug is mixed in D10W and infused over 2 hours on three consecutive days.

RTA 744

This study assesses the tolerability, safety, efficacy and pharmacokinetics of RTA 744 in recurrent neoplastic meningitis.

Neoplastic meningitis refers to the deposition of malignant cells in the lining (leptomeninges) of the brain and spine. Neoplastic meningitis from solid tumors most often occurs in patients with advanced systemic disease who have failed prior chemotherapy; it is also frequent in patients with CNS parenchymal metastasis. Patient survival remains low, and better treatments are needed to penetrate the blood brain barrier and treat the entire neuraxis.

RTA 744 is a close chemical analogue of the well characterized anti-cancer agent doxorubicin. Unlike doxorubicin, RTA 744 has shown ability to cross the blood brain barrier and to achieve high concentration in CNS tumor tissue in animal models. Dose escalation will continue as pre-determined until first occurrence of a dose-limiting toxicity. Maximum tolerated dose will be determined as defined in protocol.

Study Sponsor, originally Reata Pharmaceuticals, Inc., is now Reata Pharmaceuticals, Inc., a wholly owned subsidiary of Biogen.

A Safety Study of RTA 744 in Recurrent, Progressive or Refractory Neoplastic Meningitis

A Phase I Safety and Pharmacokinetic Study of Intravenous RTA 744 Injection in Patients With Recurrent, Progressive or Refractory Neoplastic Meningitis

In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Reata, a wholly owned subsidiary of Biogen

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Amino Acids

Erlotinib Hydrochloride

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Erlotinib 150mg/day (if no negative conversion --\> increment to 250mg/day)

Erlotinib

To assess the efficacy and safety of erlotinib for non-small cell lung cancer patients with leptomeningeal carcinomatosis

A Study to Assess the Efficacy of Erlotinib for Leptomeningeal Carcinomatosis in EGFR Mutation Positive Non-small Cell Lung Cancer

Seoul National University Hospital

Korean Cancer Study Group

Clinical Research Center for Solid Tumor, Korea

Dae Seog Heo/Professor

Rare Diseases

Astrocytoma

Oligodendroglioma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Neuroepithelioma

This is an expanded access study with ANG1005 treatment for two individual patients from Protocol ANG1005-CLN-03 with WHO Grade III Anaplastic Astrocytoma and WHO Grade III Anaplastic Oligodendroglioma and one individual patient from Protocol ANG1005-CLN-04 with Recurrent Brain Metastases and Leptomeningeal Carcinomatosis.

Expanded Access to ANG1005 for Individual Patients

Expanded Access to ANG1005 for an Individual Patient With Recurrent WHO Grade III Anaplastic Astrocytoma; Expanded Access to ANG1005 for an Individual Patient With Recurrent WHO Grade III Anaplastic Oligodendroglioma; Expanded Access to ANG1005 for an Individual Breast Cancer Patient With Recurrent Brain Metastases and Leptomeningeal Carcinomatosis.

Nivolumab

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

All patients will be treated based on their primary tumor diagnosis with a combination regimen of Nivolumab and Ipilimumab. Each treatment cycle is 6 weeks; exceptions below.

* Melanoma:

  * Nivolumab 1 mg/kg and Ipilimumab 3 mg/kg, every 3 weeks for 4 doses.
  * Followed by Nivolumab 480 mg every 4 weeks until disease progression. Each cycle of monotherapy is defined as 8 weeks.
* Non-small Cell Lung Cancer / Head and Neck Cancer:

  - Nivolumab 3 mg/kg every 2 weeks, and Ipilimumab 1 mg/kg every 6 weeks.
* Small Cell Lung Cancer / Breast Cancer / Bladder Cancer:

  * Nivolumab 1 mg/kg and Ipilimumab 3 mg/kg, every 3 weeks for 4 doses.
  * Followed by Nivolumab 240 mg every 2 weeks until disease progression.
* Renal Cell Carcinoma / Other Solid Tumors (not listed above):

  * Nivolumab 3 mg/kg and Ipilimumab 3 mg/kg, every 3 weeks for 4 doses.
  * Followed by Nivolumab 480 mg every 4 weeks until disease progression. Each cycle of monotherapy is defined as 8 weeks.

* Melanoma:

  - Combination therapy with Nivolumab 1 mg/kg for 4 doses followed by monotherapy Nivolumab 480 mg per cycle.
* Non-small Cell Lung Cancer / Head and Neck Cancer:

  - Combination therapy with Nivolumab 3 mg/kg
* Small Cell Lung Cancer / Breast Cancer / Bladder Cancer:

  - Combination therapy with Nivolumab 1 mg/kg for 4 doses followed by monotherapy Nivolumab 240 mg per cycle.
* Renal Cell Carcinoma / Other Solid Tumors (not listed above):

  * Combination therapy with Nivolumab 3 mg/kg for 4 doses followed by monotherapy Nivolumab 480 mg per cycle.

* Non-small Cell Lung Cancer / Head and Neck Cancer:

  - Combination therapy with Ipilimumab 1 mg/kg
* Small Cell Lung Cancer / Breast Cancer / Bladder Cancer:

  - Combination therapy with Ipilimumab 3 mg/kg for 4 doses
* Renal Cell Carcinoma / Other Solid Tumors (not listed above):

  * Combination therapy with Ipilimumab 3 mg/kg for 4 doses

Priscilla Brastianos, MD

This research study is studying a combination of two drugs as a possible treatment for Leptomeningeal Metastases.

The names of the study interventions involved in this study are:

* Ipilimumab
* Nivolumab

This research study is a Phase II clinical trial.

Researchers hope to study the effects of the combination of Nivolumab and Ipilimumab. Many cancers use specific pathways, such as programmed death-1 (PD-1), programmed death-ligand-1 (PD-L1), and cytotoxic T lymphocyte antigen-4 (CTLA-4), to evade the body's immune system. Nivolumab and ipilimumab work by blocking the PD-1/PD-L1 and CTLA-4 pathways and thus releasing the brakes on the immune system so it can stop or slow cancer.

The FDA (the U.S. Food and Drug Administration) has approved Nivolumab and Ipilimumab as a treatment option for melanoma, but has not approved them for use when cancer cells spread to the cerebrospinal fluid

Ipilimumab and Nivolumab in Leptomeningeal Metastases

Phase II Trial of Ipilimumab and Nivolumab in Leptomeningeal Metastases

Overall Survival (OS) is defined as the time from registration to death due to any cause, or censored at date last known alive.

Grade 3 or 4 treatment-related adverse events occurring in at least 15% of participants, based on CTCAE v4.0 criteria.

Cumulative incidence describes the average probability of developing progressive disease (PD) by immunotherapy response assessment for neuro-oncology (iRANO) criteria. PD is defined as any of the following: (1) \>/= 25% increase in 2-dimensional contrast lesions; (2) significant worsened changes on T2-weighted MRI scans; (3) new lesion; or (4) significant clinical decline. Confirmation of progressive disease is based on follow-up imaging for participants without significant clinical decline.

Cumulative incidence describes the average probability of developing progressive disease (PD) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. PD is defined as any of the following: (1) \>/= 25% increase in 2-dimensional contrast lesions; (2) significant worsened changes on T2-weighted MRI scans; (3) new lesion; or (4) significant clinical decline. Confirmation of progressive disease is based on follow-up imaging for participants without significant clinical decline.

Cerebrospinal fluid (CSF) collection and cytology is done 6-9 weeks after treatment initiation to assess for LMD response, especially complete response or partial response.

Complete Response is defined as:

* Reversion to negative CSF cytology (or NA)
* Disappearance of all disease related symptoms present prior to therapy (or NA)
* Complete disappearance of all detectable radiographic evidence of disease (or NA).

Partial Response is defined as:

* \> 50% decrease in malignant CSF cytology
* Improvement in neurologic symptoms or no worsening of symptoms
* Improvement in radiographic evidence of disease. No new sites of measurable or assessable central nervous system (CNS) disease.

Extracranial Progression-Free Survival (EPFS) is defined as the time from first dose of study drug to documented extracranial disease progression or death, whichever occurs first. Extracranial disease progression is assessed with CT scans of the chest, abdomen, and pelvis, by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria and immune-related response criteria (irRC) criteria. Progression is defined using RECIST v1.0 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The follow-up of participants who have neither died nor progressed at the time of analysis will be censored at the date of last adequate disease assessment.

Intracranial Progression-Free Survival (IPFS) is defined as the time from first dose of study drug to documented intracranial disease progression or death, whichever occurs first. Intracranial disease progression is assessed with CT or MRI scans of the brain, using the Response assessment in neuro-oncology (RANO) criteria, which defines progression as:

* ≥ 25% increase in in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline; or
* Presence of new lesions; or
* Worsening of clinical/neurologic status (unless clearly unrelated to the cancer); or
* Worsening of non-measurable disease.

The follow-up of participants who have neither died nor progressed at the time of analysis will be censored at the date of last adequate disease assessment.

Bristol-Myers Squibb

Massachusetts General Hospital

All patients will be treated with the combination regimen of Nivolumab at pre-determine dose with Ipilimumab at a pre-determine dose.This will be followed by Nivolumab Monotherapy.

Each treatment Cycle will last 6 weeks

Nivolumab

Ipilimumab

Combination Of Nivolumab With Ipilimumab

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

0 = Fully active; no performance restrictions

1 = Strenuous physical activity restricted; fully ambulatory and able to carry out light work

2 = Capable of all self-care but unable to carry out work activities.Up and about >50% of waking hrs

Eastern Cooperative Oncology Group (ECOG) performance status is a scale used to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. Scale ranges from 0 to 5 and a lower score indicates a better functional status.

Eastern Cooperative Oncology Group (ECOG) performance status

Breast Cancer

Melanoma

Anaplastic astrocytoma

Esophageal adenocarcinoma

Ependymoma

Gastroesophageal (GE) junction adenocarcinoma

Glioblastoma

Lung adenocarcinoma

Ovarian

Small cell lung carcinoma

Primary tumor diagnosis

Brain metastases at the time of leptomeningeal disease (LMD) diagnosis

Unknown

Extracranial disease at the time of leptomeningeal disease (LMD) diagnosis

Percentage of Participants With Overall Survival

Percentage of Participants With Treatment-related Adverse Events

Cumulative Incidence of Progressive Disease at 3 Months for Intracranial Sites

Cumulative Incidence of Progressive Disease at 3 Months for Extracranial Sites

Complete Response

Partial Response

Due to the clinical nature of LMD with rapidly progressive disease, the majority participants did not undergo post-treatment lumbar punctures before going off study or passing away. CSF cytology 6-9 weeks after treatment initiation was only obtained on 4 participants, which does not provide statistically meaningful interpretation of data. Individual results are reported below.

Number of Participants With Leptomeningeal Disease (LMD) Response Post-Treatment

Extracranial Progression-Free Survival

Intracranial Progression-Free Survival

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
ANG1005 in Leptomeningeal Disease From Breast Cancer	NCT03613181	Leptomeningeal ... Leptomeningeal ... Brain Metastase... HER2-negative B...	ANG1005 Physician's Bes...	18 Years -	Angiochem Inc
ANG1005 in Leptomeningeal Disease From Breast Cancer	NCT03613181	Leptomeningeal ... Leptomeningeal ... Brain Metastase... HER2-negative B...	ANG1005 Physician's Bes...	18 Years -	Angiochem Inc
A Safety Study of RTA 744 in Recurrent, Progressive or Refractory Neoplastic Meningitis	NCT00527410	Leptomeningeal ...	RTA 744	18 Years -	Biogen
A Study to Assess the Efficacy of Erlotinib for Leptomeningeal Carcinomatosis in EGFR Mutation Positive Non-small Cell Lung Cancer	NCT00830245	Leptomeningeal ... Non-small Cell ...	Erlotinib	18 Years -	Clinical Research Center for Solid Tumor, Korea
Expanded Access to ANG1005 for Individual Patients	NCT02755987	Anaplastic Astr... Anaplastic Olig... Breast Cancer W... Leptomeningeal ...	ANG1005	18 Years -	Angiochem Inc
Expanded Access to ANG1005 for Individual Patients	NCT02755987	Anaplastic Astr... Anaplastic Olig... Breast Cancer W... Leptomeningeal ...	ANG1005	18 Years -	Angiochem Inc
Ipilimumab and Nivolumab in Leptomeningeal Metastases	NCT02939300	Leptomeningeal ...	Nivolumab Ipilimumab	18 Years -	Massachusetts General Hospital
ANG1005 in Leptomeningeal Disease From Breast Cancer	NCT03613181	Leptomeningeal ... Leptomeningeal ... Brain Metastase... HER2-negative B...	ANG1005 Physician's Bes...	18 Years -	Angiochem Inc
Expanded Access to ANG1005 for Individual Patients	NCT02755987	Anaplastic Astr... Anaplastic Olig... Breast Cancer W... Leptomeningeal ...	ANG1005	18 Years -	Angiochem Inc

Spots Global Cancer Trial Database for leptomeningeal carcinomatosis