MesotheliomaPhase 1NCT03436732
Mesothelin-Targeted Immunotoxin LMB-100 in Combination With SEL-110 in Subjects With Malignant Pleural or Peritoneal Mesothelioma
A Phase 1 study testing LMB-100 and SEL-110 in people with Mesothelioma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Mesothelioma
- What is being tested?
- LMB-100 and SEL-110
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Feb 2018to 30 Apr 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed epithelial or biphasic pleural or peritoneal mesothelioma not amenable to potentially curative surgical resection. However, patients with biphasic tumors that have a more than or equal to 50% sarcomatoid component will be excluded.
- The diagnosis will be confirmed by the Laboratory of Pathology, Center for Cancer Research (CCR), National Cancer Institute (NCI).
- Archival sample or fresh biopsy or tumor effusion must be available for confirmation of diagnosis.
- 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.
- The last dose of previous therapy must have occurred at least 3 weeks prior to the start of study therapy. Palliative radiotherapy is allowed up to 2 weeks before the first LMB-100 infusion.
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- Patients for whom no standard curative therapy exists
- Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of LMB-100 + SEL-110 in patients <18 years of age, children are excluded from this study
- All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade less than or equal to 1, except alopecia (any grade) and Grade 2 peripheral neuropathy.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- Adequate hematological function: neutrophil count of more than or equal to 1.0 times 10(9) cells/L, platelet count of greater than or equal to 100,000/mcL, hemoglobin more than or equal to 9 g/dL
- Adequate liver function: Bilirubin less than or equal to 2.5 times the upper limit of normal (ULN) (excluding Gilbert's Syndrome, see below).
- Patients with Gilbert's syndrome will be eligible for the study. The diagnosis of Gilbert's syndrome is suspected in people who have persistent, slightly elevated levels of unconjugated bilirubin without any other apparent cause. A diagnosis of Gilbert's syndrome will be based on the exclusion of other diseases based on the following criteria:
- Unconjugated hyperbilirubinemia noted on several occasions
- No evidence of hemolysis (normal hemoglobin, reticulocyte count, and lactate dehydrogenase (LDH))
- Normal liver function tests
- Absence of other diseases associated with unconjugated hyperbilirubinemia
- Adequate renal function: creatinine clearance (by Cockcroft Gault formula) greater than or equal to 50 mL/min.
- Must have serum albumin > 2.5 g/dL without intravenous supplementation
- Must have left ventricular ejection fraction > 50%
- Must have an ambulatory oxygen saturation of > 90% on room air
- The effects of LMB-100 in combination with SEL-110 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry until 3 months after the last dose of study therapy. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- Ability of subject to understand and the willingness to sign a written informed consent document
Who cannot join
- Known or clinically suspected central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases. History or clinical evidence of CNS metastases unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days.
- Evidence of significant, uncontrolled concomitant diseases which could affect compliance with the protocol or interpretation of results, including significant pulmonary disease other than primary cancer, uncontrolled diabetes mellitus, and/or significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, uncontrolled arrhythmias, unstable angina, non-compensative congestive heart failure, or clinically significant pericardial effusion)
- Active or uncontrolled infections.
- Human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. HIV positive patients will be excluded due to a theoretical concern that the degree of immune suppression associated with the treatment may result in progression of HIV infection.
- Patients with prior pneumonectomy
- Prior therapy with LMB-100
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- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
- Major surgery or significant traumatic injury greater than or equal to 28 days prior to the first LMB-100 infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment
- Dementia or altered mental status that would prohibit informed consent
- Live attenuated vaccinations 14 days prior to treatment
- Pregnant women are excluded from this study because it is unknown whether LMB-100 + SEL 100 has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with LMB-100+SEL-110, breastfeeding should be discontinued if the mother is treated with LMB-100+SEL-110. These potential risks may also apply to other agents used in this study.
- Known hypersensitivity to any of the components of LMB-100 and/or SEL-110
- Presence of immunosuppressive conditions, including administration of any medications or treatments that may adversely affect the immune system such as allergy injections, immune globulin, interferon, immunomodulators, cytotoxic drugs, or systemic corticosteroids (oral or injectable) during 3 months prior to enrollment.
- Inhaled and topical corticosteroids allowed.
- Known allergy to polyethylene glycol (PEG)ylated products.
- History of anaphylactic reaction to a recombinant protein or hypersensitivity to PEG.
- Taken an investigational drug within 4 weeks prior to study drug administration or plans to take an investigational agent during the study.
- Taken a strong inhibitor or inducer of cytochrome P450 3A4 (CYP3A4) within 14 days prior to enrollment (see Flockhart Table or similarly updated source for a list of such agents)
- Taken drugs known to interact with Rapamune such as cyclosporine, diltiazem, erythromycin, ketoconazole (and other antifungals), nicardipine (and other calcium channel blockers), rifampin, verapamil within 14 days prior to enrollment
- Uncontrolled hypertension (above 150/95 mm Hg).
- History of end-stage renal disease requiring dialysis.
- Serum phosphorus less than 2.0 mg/dL
- Organ transplant recipient
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
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
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.
Read more
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.
Read the 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.
- Conditions
- Mesothelioma
- Being tested
- LMB-100, SEL-110
- Keywords
- Immunotoxin, Rapamycin, Targeted Therapy, Mesothelin
- Medical subject headings
- Mesothelioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LMB-100Drug
administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles
SEL-110Drug
administered on day 1 of each cycle for up to 4 cycles
| Study group | Role | What they receive |
|---|---|---|
| 1/Dose Escalation | Experimental | Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses Receives: Drug: LMB-100; Drug: SEL-110 |
| 2/Dose Expansion | Experimental | Dose expansion - patients with mesothelioma treated with LMB-100+SEL-110 at recommended phase 2 dose (RP2D) Receives: Drug: LMB-100; Drug: SEL-110 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Grade ≥3 Adverse Events Related to Study Drug at Dose Level 140 mcg/kg and 100 mcg/kg
Here are the grade ≥3 adverse events at each dose level assessed by the Common Terminology Criteria in Adverse Events CTCAE v5.0. 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. Grade 3 is Severe or medically significant but not immediately life-threatening;hospitalization or prolongation of hospitalization indicated; disabling;limiting self care ADL (i.e., bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. Grade 4 is life-threatening consequences;urgent intervention indicated. Grade 5 is death related to adverse event.
Measured: Day 85
Maximum Tolerated Dose (MTD)
MTD is defined as the highest tested dose of LMB-100 and SEL-110 at which no more than 1 of 6 subjects experience a dose limiting toxicity. A dose limiting toxicity is defined as any of the following: Grade 4 neutropenia for a minimum duration of 7 days. Grade 4 thrombocytopenia (≤25.0 x 10(9) cells/L), Grade 3 thrombocytopenia associated with bleeding episodes, and Grade 4 anemia. Grade ≥3 non-hematological toxicity with the exception of Alopecia (any grade), Grade 3 nausea and vomiting lasting > 48 hours despite appropriate treatment, Grade 3 diarrhea lasting for ≤ 2 days with no fever or dehydration, and laboratory values of ≥ grade 3 that are judged not clinically significant by the investigator. Any other drug related toxicity considered significant enough to be qualified as a DLT in the opinion of the principal investigator. Inability to start cycle 2 within 3 weeks after completing cycle 1 due to drug-related adverse events.
Measured: Day 21
Secondary outcomes (3)
Number of Participants With Partial Response or Complete Response (PR + CR)
Response is defined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response is at least a 30% decrease in the sum of the diameters of target lesion, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Measured: 42 days
Fraction of Participants With Detectable LMB-100 in Blood After Cycle 4
Blood is measured for a detectable level of LMB-100 in the blood. LMB-100 is either detectable in the blood or not. A detectable level of LMB-100 in the blood is considered a desirable outcome for the participant. Hence, the reverse is not a considered a desirable outcome for the participant.
Measured: Day 85
Number of Participants With Serious and Non-Serious Adverse Events
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in 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.
Measured: Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2018
- Study start28 Feb 2018
- Primary completion30 Apr 2019
- Study completion30 Apr 2019
Why it stopped: Due to fatal occurrence (pneumonitis) attributed to one of the study drugs.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MesotheliomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Raffit Hassan, M.D., National Cancer Institute (NCI)
- Investigators
- Raffit Hassan, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03436732
- Sponsor's protocol ID
- 180057
- Other IDs
- 18-C-0057
- Status last verified
- Nov 2019
- First submitted
- 16 Feb 2018
- Last updated
- 22 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03436732
- Acronym / sponsor ID
- 180057
- Conditions
- Mesothelioma
- Keywords
- Immunotoxin, Rapamycin, Targeted Therapy, Mesothelin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to fatal occurrence (pneumonitis) attributed to one of the study drugs.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 28 Feb 2018 (actual)
- Primary completion
- 30 Apr 2019 (actual)
- Study completion
- 30 Apr 2019 (actual)
- First posted
- 19 Feb 2018 (actual)
- Results
- Posted 22 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1/Dose Escalation | Experimental | Drug: LMB-100, Drug: SEL-110Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses |
| 2/Dose Expansion | Experimental | Drug: LMB-100, Drug: SEL-110Dose expansion - patients with mesothelioma treated with LMB-100+SEL-110 at recommended phase 2 dose (RP2D) |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Histologically confirmed epithelial or biphasic pleural or peritoneal mesothelioma not amenable to potentially curative surgical resection. However, patients with biphasic tumors that have a more than or equal to 50% sarcomatoid component will be excluded.
- The diagnosis will be confirmed by the Laboratory of Pathology, Center for Cancer Research (CCR), National Cancer Institute (NCI).
- Archival sample or fresh biopsy or tumor effusion must be available for confirmation of diagnosis.
- 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.
Key exclusion criteria (23 listed)
- Known or clinically suspected central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases. History or clinical evidence of CNS metastases unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days.
- Evidence of significant, uncontrolled concomitant diseases which could affect compliance with the protocol or interpretation of results, including significant pulmonary disease other than primary cancer, uncontrolled diabetes mellitus, and/or significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, uncontrolled arrhythmias, unstable angina, non-compensative congestive heart failure, or clinically significant pericardial effusion)
- Active or uncontrolled infections.
- Human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. HIV positive patients will be excluded due to a theoretical concern that the degree of immune suppression associated with the treatment may result in progression of HIV infection.
- Patients with prior pneumonectomy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LMB-100administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles | Drug | 1/Dose Escalation, 2/Dose Expansion |
| SEL-110administered on day 1 of each cycle for up to 4 cycles | Drug | 1/Dose Escalation, 2/Dose Expansion |
Primary outcome
Number of Participants With Grade ≥3 Adverse Events Related to Study Drug at Dose Level 140 mcg/kg and 100 mcg/kg
Time frame: Day 85
Here are the grade ≥3 adverse events at each dose level assessed by the Common Terminology Criteria in Adverse Events CTCAE v5.0. 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. Grade 3 is Severe or medically significant but not immediately life-threatening;hospitalization or prolongation of hospitalization indicated; disabling;limiting self care ADL (i.e., bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. Grade 4 is life-threatening consequences;urgent intervention indicated. Grade 5 is death related to adverse event.
Maximum Tolerated Dose (MTD)
Time frame: Day 21
MTD is defined as the highest tested dose of LMB-100 and SEL-110 at which no more than 1 of 6 subjects experience a dose limiting toxicity. A dose limiting toxicity is defined as any of the following: Grade 4 neutropenia for a minimum duration of 7 days. Grade 4 thrombocytopenia (≤25.0 x 10(9) cells/L), Grade 3 thrombocytopenia associated with bleeding episodes, and Grade 4 anemia. Grade ≥3 non-hematological toxicity with the exception of Alopecia (any grade), Grade 3 nausea and vomiting lasting > 48 hours despite appropriate treatment, Grade 3 diarrhea lasting for ≤ 2 days with no fever or dehydration, and laboratory values of ≥ grade 3 that are judged not clinically significant by the investigator. Any other drug related toxicity considered significant enough to be qualified as a DLT in the opinion of the principal investigator. Inability to start cycle 2 within 3 weeks after completing cycle 1 due to drug-related adverse events.
3 secondary outcomes
Number of Participants With Partial Response or Complete Response (PR + CR)
Time frame: 42 days
Fraction of Participants With Detectable LMB-100 in Blood After Cycle 4
Time frame: Day 85
Number of Participants With Serious and Non-Serious Adverse Events
Time frame: Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raffit Hassan, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LMB-100 and SEL-110 in people with Mesothelioma, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Grade ≥3 Adverse Events Related to Study Drug at Dose Level 140 mcg/kg and 100 mcg/kg (time frame: Day 85). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2019.