Neoplasms

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Mesothelioma

Mesothelioma, Malignant

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Mesothelial

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Malignant Mesothelioma

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Dexamethasone

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Ipilimumab

Dexamethasone acetate

BB 1101

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Histamine H1 Antagonists

Histamine

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LMB-100

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Immunologic Factors

Those with pleural or peritoneal mesothelioma receiving intra-tumoral administration of LMB-100 + ipilimumab for up to 4 cycles.

LMB-100 administered into lesion on days 1 and 4 during cycle 1.

Administered intravenously once per cycle up to three 21-day cycles. Administration will occur during cycles 2,3,4.

ipilimumab

Infusion related reactions precaution: All participants will be premedicated with 25-50 mg Diphenhydramine by mouth (PO) or intravenous (IV) (or alternative antihistamine at adequate dose) 30-60 minutes (+ 30 minutes) prior to each LMB-100 administration.

Infusion related reactions precaution: All participants will be premedicated with 20 mg Famotidine by mouth (PO) or intravenous (IV) (or alternative histamine H2- receptor antagonists (H2) blocker at adequate dose) 30-60 minutes (+ 30 minutes) prior to each LMB-100 administration.

Infusion related reactions precaution: All participants will be premedicated with 650 mg Acetaminophen by mouth (PO) or intravenous (IV) 30-60 minutes (+ 30 minutes) prior to each LMB-100 administration.

Additional infusion precaution at infusions of LMB-100 after Cycle 1 Day 1 (as appropriate): Dexamethasone 20 mg by mouth (PO), 6-12 hours prior to LMB-100 administration OR 10mg, intravenous (IV), 30-60 minutes prior to LMB-100 administration OR equivalent dose of another corticosteroid as clinically indicated.

As feasible at screening, Cycle 1 Day 1 and 5, Cycle 2, 3, \& 4 Day 1, and Cycle 4 Day 21 (±7 days).

Biopsy

At screening, at the end of cycles 2 \& 4 ± 7 days, Follow-Up Visit (4-6 weeks after end of treatment), and Long-Term Follow-Up (every 6-12 weeks).

FDG-PET

CT CAP

At screening, Cycle 1 Day 1, Cycles 2, 3, \& 4 Day 1 and Follow-Up Visit (4-6 weeks after end of treatment).

Echocardiogram

Raffit Hassan, M.D.

Background:

Mesothelioma is a type of cancer. It originates in cells that line human body cavities. Most people have advanced disease when they are diagnosed. Researchers want to see if a combination of drugs can help.

Objective:

To find a safe dose of LMB-100 in combination with ipilimumab when LMB-100 is injected into tumors.

Eligibility:

Adults ages 18 and older with malignant pleural or peritoneal mesothelioma, that cannot be cured with surgery and has not responded to standard first-line treatments for mesothelioma.

Design:

Participants will be screened with:

* Tumor biopsy or effusion, if needed
* Medical history
* Physical exam
* Blood and urine tests
* Imaging scans
* Heart and lung function tests
* Pregnancy test, if needed

Some screening tests will be repeated during the study.

Participants will get LMB-100 on Days 1 and 4 for up to 2 cycles. Each cycle lasts 21 days. They will stay in the hospital for about 8 days each time they get LMB-100. It will be injected into their tumor with needles.

Participants will get ipilimumab through a tube that is put in a vein. It will be given on Day 2 of the first 2 cycles and Day 1 of the next 2 cycles.

Participants will be assessed for how well they do daily activities. They will give blood and tissue samples for research.

Participants will have a safety visit 4 to 6 weeks after the last dose of the study drugs. Then they will have scans every 6 weeks until their disease gets worse. If their tumor gets bigger, they will have phone, video, or email follow-ups every 12 weeks.

Participants will be on this study for life....

Background:

LMB-100, and a closely related immunotoxin, SS1P, also targeting mesothelin, given intravenously, have been studied in Phase 1 clinical studies for mesothelioma and pancreatic cancer.

LMB-100 given intravenously results in systemic inflammation in patients, but as a single agent has limited anti-tumor efficacy.

Almost all patients develop neutralizing anti-LMB-100 antibodies after 2 cycles of therapy.

Intra-tumoral delivery of LMB-100 has been shown to induce immune cell infiltration in immune-competent mice, bearing murine malignant mesothelioma tumors. Combination with cytotoxic T-lymphocyte associated protein 4 (CTLA-4) blockage eradicates murine tumors by promoting anti-cancer immunity.

Ipilimumab is a fully human anti CTLA-4 monoclonal antibody, that is approved for treatment of melanoma and in combination with nivolumab for many solid tumors.

It is hypothesized that intra-tumoral delivery of anti-mesothelin immunotoxin LMB-100 in combination with ipilimumab will result in greater anti-tumor efficacy in patients with mesothelioma.

Objective:

To determine the safety and feasibility of intra-tumoral LMB-100 injection plus ipilimumab infusion in patients with mesothelioma

To identify the recommended phase 2 dose (RP2D) of intratumorally administered LMB-100 + ipilimumab in patients with malignant mesothelioma

Eligibility:

Histologically confirmed pleural or peritoneal mesothelioma not amenable to potentially curative surgical resection.

Have locally accessible disease suitable for intra-tumor injection of LMB-100. This includes superficial or visceral lesions.

Subjects must have received prior immune checkpoint therapy with anti-Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1) inhibitors alone or in combination with anti-CTLA4 blocking antibodies, as well as platinum-based chemotherapy.

Age \>= 18 years.

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Adequate organ and bone marrow function

Subjects with clinically significant pericardial effusion are excluded.

Chemotherapy within 3 weeks or radiotherapy within 2 weeks prior to start of study therapy, is prohibited.

Subjects with active central nervous system (CNS) metastasis are excluded.

Subjects with active autoimmune disease for which they have received systemic immunosuppressive medications during the previous 2 years (excluding daily glucocorticoid-replacement therapy for conditions such as adrenal or pituitary insufficiency) are excluded.

Subjects with active interstitial lung disease, or a history of pneumonitis or interstitial lung disease for which they had received glucocorticoids are excluded.

Design:

This is an open-label, single center phase I dose escalation study of intratumorally administered LMB-100 followed by ipilimumab in subjects with malignant mesothelioma.

Subjects will receive intratumorally administered LMB-100, beginning at dose level 1, in 21-day cycles. LMB-100 will be given on days 1 and 4 of cycle 1, and ipilimumab is given on day 1 of cycles 2-4.

Tumor biopsies will be performed prior to each administration of LMB-100, on day 1 of cycle 2 and after completion of ipilimumab therapy to evaluate changes in the tumor immune microenvironment.

Up to 14 evaluable subjects will be enrolled.

Intratumor Injection of Anti-Mesothelin Immunotoxin LMB-100 With Ipilimumab in Malignant Mesothelioma

Phase I Study of Intratumor Injection of Anti-Mesothelin Immunotoxin LMB-100 With Ipilimumab in Malignant Mesothelioma

All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

RP2D is defined as the highest dose at which fewer than 2 of 6 participants experience a dose-limiting toxicity. A dose-limiting toxicity is defined as any Grade 4 hematological toxicity lasting greater than 5 days. Grade 3 febrile neutropenia, Grade 3 thrombocytopenia associated with bleeding episodes, any Grade 3 or greater, non-hematological toxicity with the following exceptions: tumor lysis syndrome, Grade 3 electrolyte changes associated with clinically significant consequences, Grade 3 nausea and diarrhea which has not received appropriate treatment, isolated Grade 3 fever occurring within 48 hours of LMB-100 infusion and resolving within 48 hours to ≤ Grade 2 and fully resolved within 1 week, alopecia, infusion-related reactions up to and including Grade 3, asymptomatic ≥ Grade 3 lymphopenia, leukopenia, hypoalbuminemia, electrolyte abnormalities resolving within 24 hours, and increase in alkaline phosphatase.

Toxicity was assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. And Grade 5 is death related to adverse event.

Proportion of participants who experienced an objective response defined as either a partial or complete response assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Partial response is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Complete response is disappearance of all target lesions.

Duration of response is defined as the median time criteria are met for partial or complete response to the first date that recurrence or progression is documented. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Partial response is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Complete response is disappearance of all target lesions. Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progressions.

Progression free survival is defined as the median time from start of treatment to time of progression or death, whichever occurs first. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progressions.

Overall survival is defined as the median time from start of treatment to death from any cause.

National Cancer Institute (NCI)

Principal Investigator

Dose Level 1: 400 mcg LMB-100 administered per dose, dose administered on days 1 and 4 of 21-day cycle, cycle 1 in participants with pleural or peritoneal mesothelioma.

Those with pleural or peritoneal mesothelioma receiving intra-tumoral administration of LMB-100 + Ipilimumab for up to 4 cycles.

For infusion related reactions precaution, all participants will be premedicated 30-60 minutes (+ 30 minutes) prior to each LMB-100 administration with the following medications: Diphenhydramine 25-50 mg by mouth (PO) or intravenous (IV) (or alternative antihistamine at adequate dose), Famotidine 20 mg by mouth (PO) or intravenous (IV) (or alternative histamine H2- receptor antagonists (H2) blocker at adequate dose), and Acetaminophen 650 mg by mouth (PO) or intravenous (IV).

Additional infusion precaution at infusions of LMB-100 after Cycle 1 Day 1 (as appropriate): Dexamethasone 20 mg by mouth (PO), 6-12 hours prior to LMB-100 administration OR 10mg, intravenous (IV), 30-60 minutes prior to LMB-100 administration OR equivalent dose of another corticosteroid as clinically indicated.

Biopsy as feasible at screening, Cycle 1 Day 1 and 5, Cycle 2, 3, \& 4 Day 1, and Cycle 4 Day 21 (±7 days).

Dose Level 1: 400 mcg LMB-100

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Raffit Hassan

All participants that received at least one dose of both LMB-100 and Ipilimumab.

Dose Level 1: 400 mcg LMB-100 administered per dose, dose administered on days 1 and 4 of 21-day cycle, cycle 1 in participants with pleural or peritoneal mesothelioma.

Those with pleural or peritoneal mesothelioma receiving intra-tumoral administration of LMB-100 + Ipilimumab for up to 4 cycles.

For infusion related reactions precaution, all participants will be premedicated 30-60 minutes (+ 30 minutes) prior to each LMB-100 administration with the following medications: Diphenhydramine 25-50 mg by mouth (PO) or intravenous (IV) (or alternative antihistamine at adequate dose), Famotidine 20 mg by mouth (PO) or intravenous (IV) (or alternative histamine H2- receptor antagonists (H2) blocker at adequate dose), and Acetaminophen 650 mg by mouth (PO) or intravenous (IV).

Additional infusion precaution at infusions of LMB-100 after Cycle 1 Day 1 (as appropriate): Dexamethasone 20 mg by mouth (PO), 6-12 hours prior to LMB-100 administration OR 10mg, intravenous (IV), 30-60 minutes prior to LMB-100 administration OR equivalent dose of another corticosteroid as clinically indicated.

All Participants in Dose Level 1: 400 mcg LMB-100

Recommended Phase 2 Dose (RP2D) of Intratumorally Administered LMB-100 in Participants With Mesothelioma

Grade 1 Non-Serious Abdominal pain

Grade 1 Non-Serious Edema limbs

Grade 1 Non-Serious Fatigue

Grade 1 Non-Serious Hypoalbuminemia

Grade 1 Non-Serious Non-cardiac chest pain

Grade 1 Non-Serious Weight gain

Grade 2 Non-Serious Anemia

Grade 2 Non-Serious Capillary leak syndrome

Grade 2 Non-Serious Edema limbs

Grade 2 Non-Serious Hypoalbuminemia

Grade 2 Non-Serious Pneumonitis

Grade 2 Non-Serious Sinus tachycardia

Grade 3 Serious and/or Non-Serious Events

Grade 4 Serious Pericardial tamponade

Grade 5 Serious and/or Non-Serious Events

Number of Participants Who Experienced Grades 1-5 Serious and/or Non-serious Toxicity Related (= Possibly + Probably + Definitely) to LMB-100

Grade 2 Non-Serious Hypoxia

Grade 4 Serious and/or Non-Serious Events

Number of Participants Who Experienced Grades 1-5 Serious and/or Non-serious Toxicity Related (= Possibly + Probably + Definitely) to Ipilimumab

Partial Response

Complete Response

Proportion of Participants Who Experienced an Objective Response Defined as Either a Partial or Complete Response

Duration of Response

Progression Free Survival

Overall Survival

Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

Dose Level -1: 200 mcg LMB-100 administered per dose, dose administered on days 1 and 4 of 21-day cycle, cycle 1 in participants with pleural or peritoneal mesothelioma.

Those with pleural or peritoneal mesothelioma receiving intra-tumoral administration of LMB-100 + Ipilimumab for up to 4 cycles.

For infusion related reactions precaution, all participants will be premedicated 30-60 minutes (+ 30 minutes) prior to each LMB-100 administration with the following medications: Diphenhydramine 25-50 mg by mouth (PO) or intravenous (IV) (or alternative antihistamine at adequate dose), Famotidine 20 mg by mouth (PO) or intravenous (IV) (or alternative histamine H2- receptor antagonists (H2) blocker at adequate dose), and Acetaminophen 650 mg by mouth (PO) or intravenous (IV).

Additional infusion precaution at infusions of LMB-100 after Cycle 1 Day 1 (as appropriate): Dexamethasone 20 mg by mouth (PO), 6-12 hours prior to LMB-100 administration OR 10mg, intravenous (IV), 30-60 minutes prior to LMB-100 administration OR equivalent dose of another corticosteroid as clinically indicated.

Biopsy as feasible at screening, Cycle 1 Day 1 and 5, Cycle 2, 3, \& 4 Day 1, and Cycle 4 Day 21 (±7 days).

Dose Level -1: 200 mcg LMB-100

Dose Level 2: 1200 mcg LMB-100 administered per dose, dose administered on days 1 and 4 of 21-day cycle, cycle 1 in participants with pleural or peritoneal mesothelioma.

Those with pleural or peritoneal mesothelioma receiving intra-tumoral administration of LMB-100 + Ipilimumab for up to 4 cycles.

For infusion related reactions precaution, all participants will be premedicated 30-60 minutes (+ 30 minutes) prior to each LMB-100 administration with the following medications: Diphenhydramine 25-50 mg by mouth (PO) or intravenous (IV) (or alternative antihistamine at adequate dose), Famotidine 20 mg by mouth (PO) or intravenous (IV) (or alternative histamine H2- receptor antagonists (H2) blocker at adequate dose), and Acetaminophen 650 mg by mouth (PO) or intravenous (IV).

Additional infusion precaution at infusions of LMB-100 after Cycle 1 Day 1 (as appropriate): Dexamethasone 20 mg by mouth (PO), 6-12 hours prior to LMB-100 administration OR 10mg, intravenous (IV), 30-60 minutes prior to LMB-100 administration OR equivalent dose of another corticosteroid as clinically indicated.

Biopsy as feasible at screening, Cycle 1 Day 1 and 5, Cycle 2, 3, \& 4 Day 1, and Cycle 4 Day 21 (±7 days).

Dose Level 2: 1200 mcg LMB-100

Overall Study

Spots Global Cancer Trial Database for ct cap

Every month we try and update this database with for ct cap cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for ct cap

Every month we try and update this database with for ct cap cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ct cap cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.