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Mesothelin-Targeted Immunotoxin LMB-100 Alone or in Combination With Nab-Paclitaxel in People With Previously Treated Metastatic and/or Locally Advanced Pancreatic Ductal Adenocarcinoma and Mesothelin Expressing Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02810418
Recruitment Status : Active, not recruiting
First Posted : June 23, 2016
Results First Posted : February 2, 2021
Last Update Posted : February 2, 2021
Sponsor:
Information provided by (Responsible Party):
Christine Alewine, M.D., National Cancer Institute (NCI)

Brief Summary:

Background:

LMB-100 is a man-made protein designed to kill cancer cells. LMB-100 targets a cancer marker called mesothelin. Mesothelin is found on the surface of many different tumors, including pancreatic cancer, but is made by a very small number of normal tissues. Other cancers that make mesothelin include mesothelioma, cholangiocarcinoma, thymic carcinoma, ovarian, lung, gastric, endometrial, cervical, and ampullary cancers. After binding to the mesothelin on tumors, LMB-100 can attack and kill cancer cells. Researchers want to see how well it works when given with and without nab-paclitaxel, a drug which treats pancreatic cancer.

Objectives:

Arm A- To find a safe dose of LMB-100 with a fixed standard dose of nab-paclitaxel in people with advanced pancreatic cancer. To see how well the combination of the two drugs reduce tumor size.

Arm B- To find a safe dose of LMB-100 when it is given as a continuous infusion over several days.

Eligibility:

Arm A- Adults age 18 and older with advanced pancreatic cancer that has worsened after anti-cancer therapy.

Arm B- Adults age 18 and older with advanced pancreatic cancer, mesothelioma or other solid tumor that makes mesothelin that has worsened after anti-cancer therapy

Design:

Participants will be screened with medical history and physical exam. They will give blood, urine, and tissue samples. They will have scans and x-rays.

During each 21-day cycle:

  • For Arm A

    • Participants will get LMB-100 by an intravenous (IV) catheter on days 1, 3, and 5. This is a tube inserted in a vein, usually in the arm.
    • Participants will get nab-paclitaxel by IV on days 1 and 8.
  • For Arm B

    • Participants will get LMB-100 by an IV catheter as a continuous infusion beginning on day 1 and continuing for 2-4 days
    • Some participants will also get nab-paclitaxel by IV on days 1 and 8.

All participants will get this combination for up to 2 cycles or until their disease worsens or they have intolerable side effects.

Participants will have blood and urine tests and scans throughout the study.

Participants will have a safety follow-up visit 3-6 weeks after treatment ends. If their disease remains stable or improves, they will be scanned every 6 weeks until their disease gets worse. Even if their disease gets worse, they or their doctor will be called to talk about their cancer status....


Condition or disease Intervention/treatment Phase
Neoplasms Pancreatic Neoplasms Drug: LMB-100 Drug: Nab-Paclitaxel Device: Mesothelin Expression Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib/II Study of Mesothelin-Targeted Immunotoxin LMB-100 Alone or in Combination With Nab-Paclitaxel in Participants With Previously Treated Metastatic and/ or Locally Advanced Pancreatic Ductal Adenocarcinoma and Mesothelin Expressing Solid Tumors
Actual Study Start Date : August 3, 2016
Actual Primary Completion Date : January 2, 2019
Estimated Study Completion Date : January 31, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Paclitaxel

Arm Intervention/treatment
Experimental: Arm A1, Dose Level 1 (Phase 1, short infusion) 100µg/kg LMB-100

Arm A1, Dose Level 1, Phase I Short Infusion 100µg/kg LMB-100 +125mg/m^2 nab-paclitaxel

Dose level 1 (DL1) Maximum tolerated dose (MTD) determination in patients with pancreatic cancer receiving short infusion LMB-100+nabpaclitaxel

Drug: LMB-100
Arms A1 and A2 (short infusion): Administered intravenously (IV) on days 1, 3 and 5 of a 21 day cycle for a maximum of 2 cycles Arm B1 (continuous infusion): Administered IV for 24, 48, 72 or 96 hours continuously on the first 1 - 4 days or 24 hour infusions on days 1 and 4 (depending on dose level) of each 21 day cycle for a maximum of 2 cycles. Arm B2 (continuous infusion): Administered IV for 24,48, 72 or 96 hours continuously on the first 1 - 4 days or 24 hour infusions on days 1 and 4 (depending on dose level) of each 14 day cycle for a maximum of 3 cycles.

Drug: Nab-Paclitaxel
Administered intravenously (IV) on days 1 and for Arms A1, A2 and B1 on day 8 of each 14-21 day cycle for a maximum of 2 (Arms A1, A2 and B1) or 3 (Arm B2) cycles
Other Name: Abraxane

Experimental: Arm A1, Dose Level-1 (Phase 1, short infusion) 65µg/kg LMB-100
Arm A1, DL-1, Ph I Short Infusion 65µg/kg LMB-100 +125mg/m^2 nab-paclitaxel
Drug: LMB-100
Arms A1 and A2 (short infusion): Administered intravenously (IV) on days 1, 3 and 5 of a 21 day cycle for a maximum of 2 cycles Arm B1 (continuous infusion): Administered IV for 24, 48, 72 or 96 hours continuously on the first 1 - 4 days or 24 hour infusions on days 1 and 4 (depending on dose level) of each 21 day cycle for a maximum of 2 cycles. Arm B2 (continuous infusion): Administered IV for 24,48, 72 or 96 hours continuously on the first 1 - 4 days or 24 hour infusions on days 1 and 4 (depending on dose level) of each 14 day cycle for a maximum of 3 cycles.

Drug: Nab-Paclitaxel
Administered intravenously (IV) on days 1 and for Arms A1, A2 and B1 on day 8 of each 14-21 day cycle for a maximum of 2 (Arms A1, A2 and B1) or 3 (Arm B2) cycles
Other Name: Abraxane

Experimental: Arm A2 (Phase 2, short infusion) 65µg/kg LMB-100

Arm A2, Phase 2 Short Infusion 65µg/kg LMB-100 +125mg/m^2 nab-paclitaxel

Efficacy determination in patients with pancreatic cancer receiving short infusion LMB-100 + nabpaclitaxel

Drug: LMB-100
Arms A1 and A2 (short infusion): Administered intravenously (IV) on days 1, 3 and 5 of a 21 day cycle for a maximum of 2 cycles Arm B1 (continuous infusion): Administered IV for 24, 48, 72 or 96 hours continuously on the first 1 - 4 days or 24 hour infusions on days 1 and 4 (depending on dose level) of each 21 day cycle for a maximum of 2 cycles. Arm B2 (continuous infusion): Administered IV for 24,48, 72 or 96 hours continuously on the first 1 - 4 days or 24 hour infusions on days 1 and 4 (depending on dose level) of each 14 day cycle for a maximum of 3 cycles.

Drug: Nab-Paclitaxel
Administered intravenously (IV) on days 1 and for Arms A1, A2 and B1 on day 8 of each 14-21 day cycle for a maximum of 2 (Arms A1, A2 and B1) or 3 (Arm B2) cycles
Other Name: Abraxane

Experimental: Arm B1, Dose Level 2 Phase I (Continuous infusion single agent lead-in)
Arm B1, DL2, 48-hr Continuous Infusion Single Agent Lead-in 100µg/kg/day LMB-100 Maximum tolerated dose (MTD) determination in patients with pancreatic cancer receiving continuous infusion LMB-100 as single agent
Drug: LMB-100
Arms A1 and A2 (short infusion): Administered intravenously (IV) on days 1, 3 and 5 of a 21 day cycle for a maximum of 2 cycles Arm B1 (continuous infusion): Administered IV for 24, 48, 72 or 96 hours continuously on the first 1 - 4 days or 24 hour infusions on days 1 and 4 (depending on dose level) of each 21 day cycle for a maximum of 2 cycles. Arm B2 (continuous infusion): Administered IV for 24,48, 72 or 96 hours continuously on the first 1 - 4 days or 24 hour infusions on days 1 and 4 (depending on dose level) of each 14 day cycle for a maximum of 3 cycles.

Device: Mesothelin Expression
Research blood test for Arm B1 eligibility

Drug: LMB-100
A 40 mcg/kg loading dose of LMB-100 is administered over 30 minutes immediately prior to the start of each long infusion.

Experimental: Arm B1, Dose Level 1 Phase I (Continuous infusion single agent lead-in)
Arm B1, DL1, 48-hr Continuous Infusion Single Agent Lead-in 65µg/kg/day LMB-100
Drug: LMB-100
Arms A1 and A2 (short infusion): Administered intravenously (IV) on days 1, 3 and 5 of a 21 day cycle for a maximum of 2 cycles Arm B1 (continuous infusion): Administered IV for 24, 48, 72 or 96 hours continuously on the first 1 - 4 days or 24 hour infusions on days 1 and 4 (depending on dose level) of each 21 day cycle for a maximum of 2 cycles. Arm B2 (continuous infusion): Administered IV for 24,48, 72 or 96 hours continuously on the first 1 - 4 days or 24 hour infusions on days 1 and 4 (depending on dose level) of each 14 day cycle for a maximum of 3 cycles.

Device: Mesothelin Expression
Research blood test for Arm B1 eligibility

Experimental: Arm B1, Dose Level 3R Phase I (Continuous infusion single agent lead-in)
Arm B1, DL3R, 24-hr Continuous Infusion Single Agent Lead-in 100µg/kg LMB-100
Drug: LMB-100
Arms A1 and A2 (short infusion): Administered intravenously (IV) on days 1, 3 and 5 of a 21 day cycle for a maximum of 2 cycles Arm B1 (continuous infusion): Administered IV for 24, 48, 72 or 96 hours continuously on the first 1 - 4 days or 24 hour infusions on days 1 and 4 (depending on dose level) of each 21 day cycle for a maximum of 2 cycles. Arm B2 (continuous infusion): Administered IV for 24,48, 72 or 96 hours continuously on the first 1 - 4 days or 24 hour infusions on days 1 and 4 (depending on dose level) of each 14 day cycle for a maximum of 3 cycles.

Device: Mesothelin Expression
Research blood test for Arm B1 eligibility

Drug: LMB-100
A 40 mcg/kg loading dose of LMB-100 is administered over 30 minutes immediately prior to the start of each long infusion.

Experimental: Arm B2 Phase I (continuous infusion combination therapy)
Subjects with pancreatic cancer receiving continuous infusion LMB-100 combination therapy
Drug: LMB-100
Arms A1 and A2 (short infusion): Administered intravenously (IV) on days 1, 3 and 5 of a 21 day cycle for a maximum of 2 cycles Arm B1 (continuous infusion): Administered IV for 24, 48, 72 or 96 hours continuously on the first 1 - 4 days or 24 hour infusions on days 1 and 4 (depending on dose level) of each 21 day cycle for a maximum of 2 cycles. Arm B2 (continuous infusion): Administered IV for 24,48, 72 or 96 hours continuously on the first 1 - 4 days or 24 hour infusions on days 1 and 4 (depending on dose level) of each 14 day cycle for a maximum of 3 cycles.

Drug: Nab-Paclitaxel
Administered intravenously (IV) on days 1 and for Arms A1, A2 and B1 on day 8 of each 14-21 day cycle for a maximum of 2 (Arms A1, A2 and B1) or 3 (Arm B2) cycles
Other Name: Abraxane

Drug: LMB-100
A 40 mcg/kg loading dose of LMB-100 is administered over 30 minutes immediately prior to the start of each long infusion.




Primary Outcome Measures :
  1. Objective Response (OR) (Partial Responses + Complete Responses) in Phase 2 Subjects of Short Infusion LMB-100+ Nab-paclitaxel [ Time Frame: Approximately 6 weeks after the start of treatment and continuing every 6 weeks until progression or start of a new treatment, up to 1 year ]
    OR is defined as partial responses + complete response in participants in the phase 2 Arm A portion of the study assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)v1.1. Complete Response is a disappearance of all target lesions. 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

  2. Maximum Tolerated Dose (MTD) of Short Infusion LMB-100 + Nab Paclitaxel [ Time Frame: 21 days after LMB-100 is administered (end of cycle 1) ]
    MTD is defined as the highest dose tolerated without exceeding a pre-set number of adverse events in Phase 1, Arm A.

  3. Maximum Tolerated Dose (MTD) of Continuous Infusion LMB-100 [ Time Frame: 21 days after LMB-100 is administered (end of cycle 1) ]
    MTD is defined as the highest dose tolerated without exceeding a pre-set number of adverse events in Phase 1, 1 Arm B, single agent lead-in


Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: Time from treatment initiation to disease progression or death, an average of 1 year. ]
    PFS is the average time from treatment initiation to disease progression or death. Progression was assessed 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. And the appearance of one or more new lesions.

  2. Overall Survival (OS) [ Time Frame: Time from treatment initiation to death, up to 1-2 years. ]
    OS is the average time from treatment initiation to death.

  3. Proportion of Participants Disease Control Rate (DCR) at End of Treatment (EOT) [ Time Frame: up to 3 months ]
    DCR is the proportion of participants with stable disease, partial response or complete response at end of treatment. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. 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. Stable disease is neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.

  4. Number of Participants With an Objective Response (OR) (Partial Responses + Complete Responses) in Phase 1 Arm A1 [ Time Frame: Approximately 6 weeks after the start of treatment and continuing every 6 weeks until progression or start of a new treatment up to 1 year. ]
    OR is defined as partial response + complete response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)v1.1. Complete Response is a disappearance of all target lesions. 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

  5. Number of Participants With an Objective Response (OR) (Partial Response + Complete Response) in Phase 1, Arm B [ Time Frame: Approximately 6 weeks after the start of treatment and continuing every 6 weeks until progression or start of a new treatment up to 1 year. ]
    OR is defined as partial responses + complete response in participants in the phase 1 Arm B portion of the study assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)v1.1. Complete Response is a disappearance of all target lesions. 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.

  6. Number of Participants With Adverse Events Attributed to LMB-100 [ Time Frame: Date treatment consent signed to date off study, approx. 11 mos, 8 days for A1DL1; 20 mos, 9 days for A1DL-1; 10 mos, 17 days for A2; 2 mos, 16 days for B1DL1; 14 mos, 30 days for B1DL2; 5 mos, 1 day for B2; and 4 mos, 15 days for B1DL3R. ]
    Grade 1-4 adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0 observed in subjects with pancreatic cancer. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe or medically significant. Grade 4 is life-threatening consequences.

  7. Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). [ Time Frame: Date treatment consent signed to date off study, approx. 11 mos, 8 days for A1DL1; 20 mos, 9 days for A1DL-1; 10 mos, 17 days for A2; 2 mos, 16 days for B1DL1; 14 mos, 30 days for B1DL2; 5 mos, 1 day for B2; and 4 mos, 15 days for B1DL3R. ]
    Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). 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.


Other Outcome Measures:
  1. Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) [ Time Frame: First 28 days following infusion of LMB-100 on Cycle 1, Day 1 through the duration of the study treatment up to 1 year. ]
    A DLT is defined per protocol as events attributed to LMB-100 and occurring during the DLT period such as hematological toxicities: Grade 4 neutropenia, Grade 3 and 4 febrile neutropenia, Grade 4 thrombocytopenia, and Grade 3 thrombocytopenia associated with bleeding episodes. Grade ≥3 non-hematological toxicity with the exception of: Grade 3 nausea and vomiting without appropriate treatment, Grade 3 diarrhea lasting ≤2 days with no fever or dehydration, and isolated Grade 3 fever. Grade ≥4 non-hematological toxicity: infusion related reactions, and any other drug related toxicity qualified as a DLT per the discretion of the principal investigator.

  2. Area Under the Plasma Concentration vs. Time Curve Extrapolated to Infinity (AUCinf) [ Time Frame: For Arms A1 & A2: Pre-dose, end of infusion (EOI), 1, 2 and 4 hours after EOI during Cycle 1 Day 1. ]
    Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0). It is used to characterize drug absorption.

  3. Area Under the Serum Concentration Versus Time Curve Extrapolated to Infinity (AUCinf)/D (Dose) [ Time Frame: For Arms A1 & A2: Pre-dose, end of infusion (EOI), 1, 2 and 4 hours after EOI during Cycle 1 Day 1. ]
    The AUC is a measure of the serum concentration of the drug dose over time. It is used to characterize drug absorption.

  4. Area Under the Serum Concentration Versus Time Curve Extrapolated to Last Measurement (AUClast)/D [ Time Frame: For Arms B1 & B2: Pre-dose, end of loading dose, 2 and 6 hours after start of continuous infusion, end of infusion (EOI) and 2 hrs after EOI during Cycle 1 Day 1. ]
    The AUC is a measure of the serum concentration of the drug dose over time. It is used to characterize drug absorption

  5. Time Curve Extrapolated to Last Measurement (AUClast) for LMB-100 [ Time Frame: For Arms B1 & B2: Pre-dose, end of loading dose, 2 and 6 hours after start of continuous infusion, end of infusion (EOI) and 2 hrs after EOI during Cycle 1. ]
    Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated to last measurement. It is used to characterize drug absorption.

  6. The Total Clearance (CL) of LMB-100 [ Time Frame: For Arms A1 & A2: Pre-dose, end of infusion (EOI), 1, 2 and 4 hours after EOI during Cycle 1 Day 1. ]
    The CL is a quantitative measure of the rate at which a drug substance is removed from the body.

  7. Plasma Half-Life (T1/2) of LMB-100 [ Time Frame: For Arms A1 & A2: Pre-dose, end of infusion (EOI), 1, 2 and 4 hours after EOI during Cycle 1, Day 1. ]
    Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half.

  8. Volume of Distribution (Vd) of LMB-100 [ Time Frame: For Arms A1 & A2: Pre-dose, end of infusion (EOI), 1, 2 and 4 hours after EOI during Cycle 1, Day 1. ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

  9. Maximum Observed (Peak) Plasma Concentration (Cmax) of LMB-100 in Arm A1 and Arm A2 [ Time Frame: For Arms A1 & A2: Pre-dose, end of infusion (EOI), 1, 2 and 4 hours after EOI during Cycle 1 Day. Pre-dose and end of infusion (EOI) during Cycle 2 Day 1. ]
    The maximum observed analyte concentration in serum was reported.

  10. Maximum Observed (Peak) Plasma Concentration (Cmax) of LMB-100 in Arm B1 and Arm B2 [ Time Frame: For Arms B1 & B2: Pre-dose, end of loading dose, 2 and 6 hours after start of continuous infusion, end of infusion (EOI) and 2 hrs after EOI during Cycle 1 Day 1. Pre-dose, end of loading dose and EOI during Cycle 2 Day 1. ]
    The maximum observed analyte concentration in serum was reported.

  11. Maximum Observed (Peak) Plasma Concentration (Cmax)/D (Dose) of LMB-100 in Arm A1 and Arm A2 [ Time Frame: For Arms A1 & A2: Pre-dose, end of infusion (EOI), 1, 2 and 4 hours after EOI during Cycle 1 Day 1. Pre-dose and end of infusion (EOI) during Cycle 2 Day 1. ]
    The maximum observed analyte concentration of dose was reported.

  12. Maximum Observed (Peak) Plasma Concentration (Cmax)/D (Dose) of LMB-100 in Arm B1 and Arm B2 [ Time Frame: For Arms B1 & B2: Pre-dose, end of loading dose, 2 and 6 hours after start of continuous infusion, end of infusion (EOI) and 2 hrs after EOI during Cycle 1 Day 1. Pre-dose, end of loading dose and EOI during Cycle 2 Day 1. ]
    The maximum observed analyte concentration in serum was reported.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • For participants who will be receiving nab-paclitaxel (all arms except Phase I Arm B Single Agent Lead-in)

    • Histologically confirmed recurrent, advanced or metastatic pancreatic ductal adenocarcinoma as determined by National Cancer Institute (NCI) Laboratory of Pathology.
    • No treatment with paclitaxel or nab-paclitaxel within 4 months prior to initiation of study therapy
    • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
    • Adequate hematological function: neutrophil count of greater than or equal to 1.0 x 10(9) cells/L, platelet count of greater than or equal to 95,000/microliters, hemoglobin greater than or equal to 9 g/dL
    • Measurable disease as per the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria v 1.1
    • For participants who will NOT receive nab-paclitaxel (Arm B1 Single Agent Lead-in only)
    • Histologically confirmed solid tumor malignancy for which no curative therapy exists with at least 25% of tumor cells expressing mesothelin as determined by NCI Laboratory of Pathology. Determination can be made using archival tumor tissue or fresh biopsy. Subjects with epithelioid mesothelioma and pancreatic adenocarcinoma are automatically eligible and are not required to have this test.
    • ECOG performance status (PS) 0-2.
    • Adequate hematological function: neutrophil count of greater than or equal to 1.0 x 10(9) cells/L, platelet count of greater than or equal to 85,000/microliters, hemoglobin greater than or equal to 8.5 g/dL
    • Measurable and/or evaluable disease as per the RECIST Criteria v 1.1
  • For all arms of the protocol

    • Participants must have received at least one prior chemotherapy regimen for their disease.
    • 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 combination with nab-paclitaxel in persons <18 years of age, children are excluded from this study.
    • Participants must be more than 14 days removed from most recent minor surgical procedure (such as biliary stenting), 28 days from most recent major surgical procedure, 14 days removed from most recent radiation therapy, chemotherapy or experimental drug treatment with published half-life known to be 72 hours or less and 28 days removed from last experimental drug treatment with unpublished or half-life greater than 72 hours.
    • All acute toxic effects of any prior radiotherapy, chemotherapy, experimental drug treatment or surgical procedure must have resolved to Grade less than or equal to 1, except alopecia (any grade) and peripheral neuropathy.
    • Serum albumin greater than or equal to 2.5 mg/dL without intravenous supplementation
    • Adequate liver function: Bilirubin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x upper limit of normal (ULN). AST and ALT up to 5x ULN is permitted for patients with liver metastases.
    • Adequate renal function: creatinine clearance greater than or equal to 50 mL/min.
    • Must have left ventricular ejection fraction > 50%
    • Must have an ambulatory oxygen saturation of > 88% on room air
    • The effects of LMB-100 alone or in combination with nab-paclitaxel 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 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 participant to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

  • Exclusion criteria for all study arms

    • Known or clinically suspected central nervous system (CNS) 2.1.2.1 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 that related to the 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)
    • Any known diagnoses, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition (other than pancreatic adenocarcinoma) that would contraindicate the use of an investigational drug, interfere with tumor measurement or lead to an expected life expectancy of less than 6 months as judged by the investigator
    • Active or uncontrolled infections.
    • Live attenuated vaccinations within 14 days prior to treatment
    • Dementia or altered mental status that would prohibit informed consent
    • Pregnant women are excluded from this study because the effects of LMB-100 on the developing fetus are unknown and may have the potential to cause 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, 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
    • Baseline corrected QT interval by Fridericia (QTcF) interval of > 470 ms, participants with baseline resting bradycardia < 45 beats per minute, or baseline resting tachycardia> 100 beats per minute.
  • Exclusion criteria specific to patients who will be receiving nab-paclitaxel (all arms except Arm B1 Single Agent Lead-in)

    • Participants with contra-indication and/or history of severe hypersensitivity reactions to nab-paclitaxel
    • Participants with baseline peripheral neuropathy greater than grade 2
    • Human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection due to risk of progression while receiving immunosuppressive chemotherapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02810418


Locations
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United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Christine C Alewine, M.D. National Cancer Institute (NCI)
  Study Documents (Full-Text)

Documents provided by Christine Alewine, M.D., National Cancer Institute (NCI):
Informed Consent Form: Screening Consent  [PDF] December 13, 2018

Additional Information:
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Responsible Party: Christine Alewine, M.D., Principal Investigator, National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02810418    
Other Study ID Numbers: 160128
16-C-0128
First Posted: June 23, 2016    Key Record Dates
Results First Posted: February 2, 2021
Last Update Posted: February 2, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Keywords provided by Christine Alewine, M.D., National Cancer Institute (NCI):
Immunotoxin
Mesothelin
Antibody-based Therapeutics
Advanced Cancer
Additional relevant MeSH terms:
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Neoplasms
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action