Neoplasms

Symptoms and General Pathology

All Conditions

Nervous System Diseases

Neoplasm Metastasis

Meningeal Carcinomatosis

Carcinoma

Neoplastic Processes

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Meningeal Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

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.

Spots Global Cancer Trial Database for Ipilimumab and Nivolumab in Leptomeningeal Metastases

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial