MesotheliomaPhase 1NCT02798536
Mesothelin-Targeted Immunotoxin LMB-100 in People With Malignant Mesothelioma
A Phase 1 study testing LMB-100 and nab-paclitaxel in people with Mesothelioma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: LMB-100 is a man-made protein. It is attracted to the mesothelin protein. This is found in many tumors, including mesothelioma. But it is found in only a very small number of normal tissues. After binding to mesothelin on tumors, LMB-100 attacks and kills cancer cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mesothelioma
- What is being tested?
- LMB-100 and nab-paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Jul 2016to 21 Apr 2022
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed epithelial or biphasic 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, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as greater than or equal to 20 mm with conventional techniques or as greater than or equal to10 mm with spiral computed tomography (CT) scan.
- 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.
- Patients for whom no standard curable therapy exists
Show all 26Show fewer
- Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of LMB-100 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 (ECOG) performance status (PS) 0 or1
- Adequate hematological function: neutrophil count of more than of equal to 1.5x10^9 cells/L, platelet count of greater than or equal to 100,000/microl, (transfusion independent, defined as not receiving platelet transfusions within 7 days prior to laboratory sample) hemoglobin more than or equal to 9 g/dL
- Adequate Liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5 X upper limit of normal alkaline phosphate less than 2.5 X upper limit of normal unless bone metastasis is present (less than 5 X upper limit of normal) in the absence of liver metastasis.
- Bilirubin less than or equal to 1.5 mg/dL (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 less than 1.5 mg/dL OR creatinine clearance (by Cockcroft Gault formula) greater than or equal to 50 mL/min.
- Must have serum albumin > 2.5 mg/dL without intravenous supplementation
- Must have left ventricular ejection fraction > 50%
- Must have an ambulatory oxygen saturation of > 90% on room air
- Women of child-bearing potential (defined as a sexually mature woman who (1) has not undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy [the surgical removal of both ovaries] or; (2) has not been naturally postmenopausal for at least 24 consecutive months [i.e., has had menses at any time during the preceding 24 consecutive months]) must:
- Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis), or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting study therapy (including dose interruptions), while on study medication and for 3 months after the last dose of study therapy; and
- Have a negative serum pregnancy test (<= -human chorionic gonadotropin (hCG) result at screening and agree to ongoing pregnancy testing during the course of the study, and after the end of study therapy. This applies even if the subject practices true abstinence* from heterosexual contact.
- Men must agree to practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following discontinuation of study therapy, even if he has undergone a successful vasectomy.
- 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, unstable arrhythmias, unstable angina, 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
- 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
Show all 14Show fewer
- 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
- Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with LMB-100, breastfeeding should be discontinued if the mother is treated with LMB-100. These potential risks may also apply to other agents used in this study.
- Known hypersensitivity to any of the components of LMB-100
- High doses of systemic corticosteroids within 7 days prior to first dosing. High dose is considered as > 20 mg of dexamethasone a day (or equivalent) for > 7 consecutive days.
- Subjects must not have received paclitaxel nor nab-paclitaxel within 4 months prior to initiation of study therapy.
- Participants with contra-indication and/or history of sever hypersensitivity reactions to nab-paclitaxel.
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 With or Without Nab-Paclitaxel (Abraxane) in Patients With Malignant Mesothelioma
Background:
LMB-100 is a man-made protein. It is attracted to the mesothelin protein. This is found in many tumors, including mesothelioma. But it is found in only a very small number of normal tissues. After binding to mesothelin on tumors, LMB-100 attacks and kills cancer cells. Researchers want to test LMB-100 in people with advanced mesothelioma.
Read more
Objective:
To find a safe dose and anti-tumor activity of LMB-100 for people with advanced mesothelioma.
Eligibility:
Adults ages 18 and older with:
Advanced pleural or peritoneal mesothelioma that has not responded to platinum-based
therapy
Adequate organ function
Design:
Participants will be screened with:
Samples of tumor tissue or tumor fluid. These can be new or from a previous procedure.
Medical history
Physical exam
Blood, urine, and heart tests
Chest x-rays
Computed tomography (CT) or magnetic resonance imaging (MRI) scans
Fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans
Participants will get LMB-100 on days 1, 3, and 5 of each 21-day cycle. It will be given through an intravenous (IV) catheter, a tube inserted in an arm vein. They will get standard medicines before each infusion to help prevent side effects. Each infusion lasts about 30 minutes. They will be monitored for up to 2 hours after.
During each cycle, participants will repeat the screening tests.
Participants will get the study drug for up to 4 cycles or until their disease worsens or they have intolerable side effects.
About 4-6 weeks after their last infusion, participants will have a follow-up visit. They will repeat the study tests.
Participants will have follow-up scans every 6 weeks until their disease gets worse.
Participants will be called about once a year to see how they are doing.
Read the detailed description
Background:
- Although mesothelioma patients with a limited tumor burden may benefit from surgical resection, most patients have advanced disease at diagnosis and are not candidates for cytoreductive surgery.
- For mesothelioma patients who are not eligible for curative surgery, the median survival with supportive care alone is 6 months whereas with the current standard treatment, a combination of cisplatin and pemetrexed, the median survival is 12 months.
- Mesothelin, a tumor differentiation antigen, is expressed in over 95% of epitheloid mesothelioma. Mesothelin is a suitable candidate for targeted therapy due to its very limited expression in normal human tissue and its high expression in several tumors including mesothelioma.
- LMB-100 is a novel recombinant anti-mesothelin immunotoxin developed for the treatment of patients with solid tumors that express mesothelin. Mesothelin is targeted by linking a humanized fragment of the anti-mesothelin Fab to a de-immunized Pseudomonas exotoxin (PE).
- The clinical use of first generation immunotoxins such as SS1P was hampered mainly by their high immunogenicity. LMB-100 is a next generation PE-fusion protein that has been protein-engineered to maximally reduce its immunogenicity. LMB-100 has shown broad activity against different mesothelin expressing cancer cell lines and tumor xenograft models.
Objectives: Phase 1
To identify the recommended phase 2 dose (RP2D) of LMB-100 in patients with treatment refractory advanced epithelioid or biphasic mesothelioma and evaluate potential efficacy of the identified RP2D.
-Phase 2
To determine the efficacy of LMB-100 with respect to objective response rate in patients with treatment refractory advanced epithelioid or biphasic mesothelioma.
Eligibility:
- Age greater than or equal to 18 years
- Histologically confirmed advanced pleural or peritoneal mesothelioma
- Subjects must have had at least 1 prior chemotherapy regimen with last dose of previous therapy occurring at 3 weeks before the start of study treatment
- Adequate organ function
- Participants with central nervous system (CNS) metastases or prior pneumonectomy are excluded
Design:
- This is a Phase I, open-label study to evaluate the safety, pharmacokinetics, and activity of LMB-100 in patients with treatment refractory advanced epithelioid or biphasic mesothelioma.
- LMB-100 will be administered intravenously on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles
- Tumor response will be assessed after every 2 cycles
- Optional tumor biopsies may be collected at baseline and after 2 cycles of therapy
- The accrual ceiling will be set at 30
- Conditions
- Mesothelioma
- Being tested
- LMB-100, nab-paclitaxel
- Keywords
- Immunotoxin, Mesothelin, Targeted Therapy
- 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 intravenous (IV) on days 1, 3 and 5 of a 21 day cycle for up to 4 cycles (Arms A1 and A2) or 2 cycles (Arms B1 and B2)
nab-paclitaxelDrug
Arms B1 and B2 only. Administered intravenous (IV) on days 1 and 8 of each 21 day cycle for up to 6 cycles
| Study group | Role | What they receive |
|---|---|---|
| A1/LMB-100 dose escalation (closed) | Experimental | De-escalating doses of LMB-100 in up to 18 subjects Receives: Drug: LMB-100 |
| A2/LMB-100 dose expansion (closed) | Experimental | Fixed dose of LMB-100 as determined in Arm A1 in up to 16 subjects Receives: Drug: LMB-100 |
| B1/LMB-100+ nab- paclitaxel dose escalation | Experimental | De-escalating doses of LMB-100 + fixed dose of nab-paclitaxel in up to 12 subjects Receives: Drug: LMB-100; Drug: nab-paclitaxel |
| B2/LMB-100+ nab- paclitaxel dose expansion | Experimental | Fixed dose of LMB-100 as determined in Arm B1 + fixed dose of nab-paclitaxel in up to 16 subjects Receives: Drug: LMB-100; Drug: nab-paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended Phase 2 Dose (RP2D) of LMB100 + Nab-paclitaxel
Highest administered dose of LMB-100 + nab-paclitaxel at which no more than 1 of 6 participants experiences a dose limiting toxicity (DLT). A DLT is any of the following events attributed to LMB-100 and occurring within 21 days after the first dose of LMB-100 such as Grade 4 neutropenia, Grade 3 and 4 febrile neutropenia, Grade 4 thrombocytopenia, Grade 3 thrombocytopenia associated with bleeding episodes. Grade ≥ 3 non-hematological toxicity with the exception of alopecia (any grade), Grade 3 nausea and vomiting without appropriate treatment, Grade 3 diarrhea lasting for ≤ 2 days with no fever or dehydration.
Measured: 3 weeks after initial dose
Secondary outcomes (7)
Number of Participants at Recommended Phase 2 Dose (RP2D) With Partial or Complete Response by the Response Evaluation Criteria in Solid Tumors (RECIST)
Number of participants at maximum tolerated dose (MTD) with partial or complete response measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. 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.
Measured: End of treatment, an average of 57.6 days
Median Progression Free Survival (PFS)
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.
Measured: At progression, up to 3.6 months
Median Overall Survival (OS)
OS is defined as the duration of time from start of treatment to time of death.
Measured: At death, up to 60.8 months
Number of Participants With LMB-100 Maximum Observed Serum Concentration (Cmax) of >100ng/mL
Number of participants with LMB-100 Maximum observed serum concentration (Cmax) of >100ng/mL was measured by
Measured: Cycle 1 and Cycle 2 (each cycle is 21 days), approximately 42 days
Number of Participants With Anti-drug Antibodies (ADAs) Formation to LMB-100
ADAs formation to LMB-100 were measured by the enzyme-linked immunosorbent assay (ELISA). The presence of ADAs (i.e., positive) may indicate the participant may have poor blood levels.
Measured: Cycle 1 and Cycle 2 (each cycle is 21 days), approximately 42 days
Number of Grade 3-5 Adverse Events Possibly, Probably, and/or Definitely Related to the LMB-100 +/- Nab-Paclitaxel
Adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 3 is serious, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.
Measured: 30 days after treatment
Duration of Response (DOR)
The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Progressive disease was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) and is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.
Measured: time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented by computed tomography (CT) scans performed every 6 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2016 (estimated)
- Study start27 Jul 2016
- Primary completion20 Jul 2017
- Study completion21 Apr 2022
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
- 21 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
- NCT02798536
- Sponsor's protocol ID
- 160127
- Other IDs
- 16-C-0127
- Status last verified
- Jul 2022
- First submitted
- 10 Jun 2016
- Last updated
- 23 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2022. 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 With or Without Nab-Paclitaxel (Abraxane) in Patients With Malignant Mesothelioma
- ClinicalTrials.gov ID
- NCT02798536
- Acronym / sponsor ID
- 160127
- Conditions
- Mesothelioma
- Keywords
- Immunotoxin, Mesothelin, Targeted Therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 27 Jul 2016 (actual)
- Primary completion
- 20 Jul 2017 (actual)
- Study completion
- 21 Apr 2022 (actual)
- First posted
- 14 Jun 2016 (estimated)
- Results
- Posted 23 Aug 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
LMB-100 is a man-made protein. It is attracted to the mesothelin protein. This is found in many tumors, including mesothelioma. But it is found in only a very small number of normal tissues. After binding to mesothelin on tumors, LMB-100 attacks and kills cancer cells. Researchers want to test LMB-100 in people with advanced mesothelioma.
Objective:
To find a safe dose and anti-tumor activity of LMB-100 for people with advanced mesothelioma.
Eligibility:
Adults ages 18 and older with:
Advanced pleural or peritoneal mesothelioma that has not responded to platinum-based
therapy
Adequate organ function
Design:
Participants will be screened with:
Samples of tumor tissue or tumor fluid. These can be new or from a previous procedure.
Medical history
Physical exam
Blood, urine, and heart tests
Chest x-rays
Computed tomography (CT) or magnetic resonance imaging (MRI) scans
Fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans
Participants will get LMB-100 on days 1, 3, and 5 of each 21-day cycle. It will be given through an intravenous (IV) catheter, a tube inserted in an arm vein. They will get standard medicines before each infusion to help prevent side effects. Each infusion lasts about 30 minutes. They will be monitored for up to 2 hours after.
During each cycle, participants will repeat the screening tests.
Participants will get the study drug for up to 4 cycles or until their disease worsens or they have intolerable side effects.
About 4-6 weeks after their last infusion, participants will have a follow-up visit. They will repeat the study tests.
Participants will have follow-up scans every 6 weeks until their disease gets worse.
Participants will be called about once a year to see how they are doing.
Detailed description
Background:
- Although mesothelioma patients with a limited tumor burden may benefit from surgical resection, most patients have advanced disease at diagnosis and are not candidates for cytoreductive surgery.
- For mesothelioma patients who are not eligible for curative surgery, the median survival with supportive care alone is 6 months whereas with the current standard treatment, a combination of cisplatin and pemetrexed, the median survival is 12 months.
- Mesothelin, a tumor differentiation antigen, is expressed in over 95% of epitheloid mesothelioma. Mesothelin is a suitable candidate for targeted therapy due to its very limited expression in normal human tissue and its high expression in several tumors including mesothelioma.
- LMB-100 is a novel recombinant anti-mesothelin immunotoxin developed for the treatment of patients with solid tumors that express mesothelin. Mesothelin is targeted by linking a humanized fragment of the anti-mesothelin Fab to a de-immunized Pseudomonas exotoxin (PE).
- The clinical use of first generation immunotoxins such as SS1P was hampered mainly by their high immunogenicity. LMB-100 is a next generation PE-fusion protein that has been protein-engineered to maximally reduce its immunogenicity. LMB-100 has shown broad activity against different mesothelin expressing cancer cell lines and tumor xenograft models.
Objectives: Phase 1
To identify the recommended phase 2 dose (RP2D) of LMB-100 in patients with treatment refractory advanced epithelioid or biphasic mesothelioma and evaluate potential efficacy of the identified RP2D.
-Phase 2
To determine the efficacy of LMB-100 with respect to objective response rate in patients with treatment refractory advanced epithelioid or biphasic mesothelioma.
Eligibility:
- Age greater than or equal to 18 years
- Histologically confirmed advanced pleural or peritoneal mesothelioma
- Subjects must have had at least 1 prior chemotherapy regimen with last dose of previous therapy occurring at 3 weeks before the start of study treatment
- Adequate organ function
- Participants with central nervous system (CNS) metastases or prior pneumonectomy are excluded
Design:
- This is a Phase I, open-label study to evaluate the safety, pharmacokinetics, and activity of LMB-100 in patients with treatment refractory advanced epithelioid or biphasic mesothelioma.
- LMB-100 will be administered intravenously on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles
- Tumor response will be assessed after every 2 cycles
- Optional tumor biopsies may be collected at baseline and after 2 cycles of therapy
- The accrual ceiling will be set at 30
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| A1/LMB-100 dose escalation (closed) | Experimental | Drug: LMB-100De-escalating doses of LMB-100 in up to 18 subjects |
| A2/LMB-100 dose expansion (closed) | Experimental | Drug: LMB-100Fixed dose of LMB-100 as determined in Arm A1 in up to 16 subjects |
| B1/LMB-100+ nab- paclitaxel dose escalation | Experimental | Drug: LMB-100, Drug: nab-paclitaxelDe-escalating doses of LMB-100 + fixed dose of nab-paclitaxel in up to 12 subjects |
| B2/LMB-100+ nab- paclitaxel dose expansion | Experimental | Drug: LMB-100, Drug: nab-paclitaxelFixed dose of LMB-100 as determined in Arm B1 + fixed dose of nab-paclitaxel in up to 16 subjects |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Histologically confirmed epithelial or biphasic 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, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as greater than or equal to 20 mm with conventional techniques or as greater than or equal to10 mm with spiral computed tomography (CT) scan.
- 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.
Key exclusion criteria (14 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, unstable arrhythmias, unstable angina, 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 intravenous (IV) on days 1, 3 and 5 of a 21 day cycle for up to 4 cycles (Arms A1 and A2) or 2 cycles (Arms B1 and B2) | Drug | A1/LMB-100 dose escalation (closed), A2/LMB-100 dose expansion (closed), B1/LMB-100+ nab- paclitaxel dose escalation, B2/LMB-100+ nab- paclitaxel dose expansion |
| nab-paclitaxelArms B1 and B2 only. Administered intravenous (IV) on days 1 and 8 of each 21 day cycle for up to 6 cycles | Drug | B1/LMB-100+ nab- paclitaxel dose escalation, B2/LMB-100+ nab- paclitaxel dose expansion |
Primary outcome
Recommended Phase 2 Dose (RP2D) of LMB100 + Nab-paclitaxel
Time frame: 3 weeks after initial dose
Highest administered dose of LMB-100 + nab-paclitaxel at which no more than 1 of 6 participants experiences a dose limiting toxicity (DLT). A DLT is any of the following events attributed to LMB-100 and occurring within 21 days after the first dose of LMB-100 such as Grade 4 neutropenia, Grade 3 and 4 febrile neutropenia, Grade 4 thrombocytopenia, Grade 3 thrombocytopenia associated with bleeding episodes. Grade ≥ 3 non-hematological toxicity with the exception of alopecia (any grade), Grade 3 nausea and vomiting without appropriate treatment, Grade 3 diarrhea lasting for ≤ 2 days with no fever or dehydration.
7 secondary outcomes
Number of Participants at Recommended Phase 2 Dose (RP2D) With Partial or Complete Response by the Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: End of treatment, an average of 57.6 days
Median Progression Free Survival (PFS)
Time frame: At progression, up to 3.6 months
Median Overall Survival (OS)
Time frame: At death, up to 60.8 months
Number of Participants With LMB-100 Maximum Observed Serum Concentration (Cmax) of >100ng/mL
Time frame: Cycle 1 and Cycle 2 (each cycle is 21 days), approximately 42 days
Number of Participants With Anti-drug Antibodies (ADAs) Formation to LMB-100
Time frame: Cycle 1 and Cycle 2 (each cycle is 21 days), approximately 42 days
Number of Grade 3-5 Adverse Events Possibly, Probably, and/or Definitely Related to the LMB-100 +/- Nab-Paclitaxel
Time frame: 30 days after treatment
Duration of Response (DOR)
Time frame: time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented by computed tomography (CT) scans performed every 6 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.
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Peritoneal Mesothelioma, Peritoneal Carcinomatosis
RecruitingPhase 1/2
A 2-part Phase 1/2 Open-label Trial on ODM-212
Mesothelioma, Pancreatic Cancer
RecruitingPhase 1/2
Rinatabart Sesutecan (Rina-S, PRO1184, GEN1184) for Advanced Solid Tumors (GCT1184-01/ PRO1184-001)
High Grade Epithelial Ovarian Cancer, High Grade Serous Ovarian Cancer
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 nab-paclitaxel 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 26 inclusion and 14 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: finished, as of the sponsor's last update on 23 Aug 2022. 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 23 Aug 2022). 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?
Recommended Phase 2 Dose (RP2D) of LMB100 + Nab-paclitaxel (time frame: 3 weeks after initial dose). 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 23 Aug 2022.