Ignite Creation Date:
2025-12-24 @ 9:28 PM
Ignite Modification Date:
2025-12-25 @ 7:14 PM
Study NCT ID:
NCT03436732
Status:
TERMINATED
Last Update Posted:
2019-11-22
First Post:
2018-02-16
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Mesothelin-Targeted Immunotoxin LMB-100 in Combination With SEL-110 in Subjects With Malignant Pleural or Peritoneal Mesothelioma
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase I Study of the Mesothelin-Targeted Immunotoxin LMB-100 in Combination With SEL-110 in Subjects With Malignant Pleural or Peritoneal Mesothelioma
Status:
TERMINATED
Status Verified Date:
2019-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Due to fatal occurrence (pneumonitis) attributed to one of the study drugs.
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background:
Mesothelioma is cancer of the tissue that lines some organs. A new drug, LMB-100, may bind to a protein on mesothelioma tumors and kill cancer cells. But sometimes the body makes antibodies that reduce how well LMB-100 works. Researchers want to see if adding the drug SEL-110 to LMB-100 will prevent these antibodies from forming.
Objective:
To learn how safe and tolerable LMB-100 plus SEL-110 is in people with advanced mesothelioma.
Eligibility:
Adults ages 18 and older who have pleural or peritoneal mesothelioma that has not responded to prior platinum-based therapy
Design:
Participants will be screened with
* Medical history
* Physical exam
* Blood and urine tests
* Sample of tumor tissue. This can be from a previous procedure.
* Scan of the chest, abdomen, and pelvis. Participants will lie on a table in a scanner that takes pictures. A special dye may be injected in a vein.
* Positron emission tomography (fludeoxyglucose positron emission tomography (FDG-PET)) scan. A sugar attached to a chemical that gives off a signal will be injected before the scan.
* Heart function tests
The study will be done in 21-day cycles. Participants will get the study drugs for up to 4 cycles. They will get them through an intravenous (IV) catheter (a tube inserted in a vein, usually in the arm):
* LMB-100 for about 30 minutes on day 1, day 3, and day 5 of each cycle
* SEL-110 for about 1 hour on day 1 of each cycle
Participants will get standard medicines to help prevent side effects.
Participants will repeat some screening tests during each cycle and about 5 weeks after the last dose of study drug.
Mesothelioma is cancer of the tissue that lines some organs. A new drug, LMB-100, may bind to a protein on mesothelioma tumors and kill cancer cells. But sometimes the body makes antibodies that reduce how well LMB-100 works. Researchers want to see if adding the drug SEL-110 to LMB-100 will prevent these antibodies from forming.
Objective:
To learn how safe and tolerable LMB-100 plus SEL-110 is in people with advanced mesothelioma.
Eligibility:
Adults ages 18 and older who have pleural or peritoneal mesothelioma that has not responded to prior platinum-based therapy
Design:
Participants will be screened with
* Medical history
* Physical exam
* Blood and urine tests
* Sample of tumor tissue. This can be from a previous procedure.
* Scan of the chest, abdomen, and pelvis. Participants will lie on a table in a scanner that takes pictures. A special dye may be injected in a vein.
* Positron emission tomography (fludeoxyglucose positron emission tomography (FDG-PET)) scan. A sugar attached to a chemical that gives off a signal will be injected before the scan.
* Heart function tests
The study will be done in 21-day cycles. Participants will get the study drugs for up to 4 cycles. They will get them through an intravenous (IV) catheter (a tube inserted in a vein, usually in the arm):
* LMB-100 for about 30 minutes on day 1, day 3, and day 5 of each cycle
* SEL-110 for about 1 hour on day 1 of each cycle
Participants will get standard medicines to help prevent side effects.
Participants will repeat some screening tests during each cycle and about 5 weeks after the last dose of study drug.
Detailed Description:
Background:
* LMB-100 and a closely related immunotoxin also targeting mesothelin have been studied in previous Phase 1 clinical studies for mesothelioma and pancreatic cancer.
* Results from these studies showed that the majority of patients formed anti-drug-antibodies (ADAs) that neutralized subsequent injection of the product making it ineffective.
* In a small subset of patients that did not form ADAs to the product, good response and regression of tumors was seen.
* In a different application SEL-110, a biodegradable nanoparticle containing rapamycin, has been shown in clinical trials to prevent the formation of ADAs to an immunogenic enzyme when co-administered. Preclinical data show that SEL-110 also prevents the formation of ADAs to LMB-100.
* This clinical trial will investigate whether SEL-110 when administered with LMB-100 is able to prevent the formation of ADAs and thus allow patients to receive multiple, effective injections of LMB-100.
Objectives:
-The primary objective of the study is to assess the safety and tolerability of LMB-100 in combination with SEL-110.
Eligibility:
Primary Inclusion Criteria
* Greater than or equal to 18 years of age
* Histologically confirmed epithelial or biphasic pleural or peritoneal mesothelioma not amenable to potentially curative surgical resection.
* Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
* Patients must have had at least one prior chemotherapy regimen that includes pemetrexed and cisplatin or carboplatin. There is no limit to the number of prior chemotherapy regimens received.
* Patients for whom no standard curative therapy exists
Primary Exclusion Criteria:
* Known or clinically suspected central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases.
* Evidence of significant, uncontrolled concomitant diseases which could affect compliance with the protocol or interpretation of results.
* Evidence of active or uncontrolled infections.
* Live attenuated vaccinations 14 days prior to treatment
* Pregnant women are excluded from this study
Design:
* This is a Phase I, single center, dose escalation study of LMB-100 in combination with SEL-110
* Patients will receive the combination using a dose escalation scheme in which different doses of LMB100 and SEL-110 will be evaluated.
* Patients will receive 4 cycles of LMB-100 with SEL-110. A cycle will consist of intravenous (i.v.) infusion of SEL-110 on Day 1 of the cycle followed immediately by an i.v. infusion of LMB-100, then on Days 3 and 5 of the cycle patients will receive an i.v. infusion of LMB-100 only. Treatment cycles will be separated by 21 days.
* LMB-100 and a closely related immunotoxin also targeting mesothelin have been studied in previous Phase 1 clinical studies for mesothelioma and pancreatic cancer.
* Results from these studies showed that the majority of patients formed anti-drug-antibodies (ADAs) that neutralized subsequent injection of the product making it ineffective.
* In a small subset of patients that did not form ADAs to the product, good response and regression of tumors was seen.
* In a different application SEL-110, a biodegradable nanoparticle containing rapamycin, has been shown in clinical trials to prevent the formation of ADAs to an immunogenic enzyme when co-administered. Preclinical data show that SEL-110 also prevents the formation of ADAs to LMB-100.
* This clinical trial will investigate whether SEL-110 when administered with LMB-100 is able to prevent the formation of ADAs and thus allow patients to receive multiple, effective injections of LMB-100.
Objectives:
-The primary objective of the study is to assess the safety and tolerability of LMB-100 in combination with SEL-110.
Eligibility:
Primary Inclusion Criteria
* Greater than or equal to 18 years of age
* Histologically confirmed epithelial or biphasic pleural or peritoneal mesothelioma not amenable to potentially curative surgical resection.
* Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
* Patients must have had at least one prior chemotherapy regimen that includes pemetrexed and cisplatin or carboplatin. There is no limit to the number of prior chemotherapy regimens received.
* Patients for whom no standard curative therapy exists
Primary Exclusion Criteria:
* Known or clinically suspected central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases.
* Evidence of significant, uncontrolled concomitant diseases which could affect compliance with the protocol or interpretation of results.
* Evidence of active or uncontrolled infections.
* Live attenuated vaccinations 14 days prior to treatment
* Pregnant women are excluded from this study
Design:
* This is a Phase I, single center, dose escalation study of LMB-100 in combination with SEL-110
* Patients will receive the combination using a dose escalation scheme in which different doses of LMB100 and SEL-110 will be evaluated.
* Patients will receive 4 cycles of LMB-100 with SEL-110. A cycle will consist of intravenous (i.v.) infusion of SEL-110 on Day 1 of the cycle followed immediately by an i.v. infusion of LMB-100, then on Days 3 and 5 of the cycle patients will receive an i.v. infusion of LMB-100 only. Treatment cycles will be separated by 21 days.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 18-C-0057 | None | None | View |