Clinical Trials /

A Clinical Trial Evaluating the Safety of Combining Lutathera(R) and Azedra(R) to Treat Mid-gut Neuroendocrine Tumors

NCT04614766

Description:

This study is designed to identify the best tolerated doses of Lutathera® and Azedra® when co-administered to treat midgut neuroendocrine tumors. These drugs are radioactive drugs, known as radionuclide therapy, and are both approved in the treatment of midgut neuroendocrine tumor as single agents (not together). Currently, the safest and best tolerated doses of these drugs (when combined) is unknown. That is the purpose of this clinical trial.

Related Conditions:
  • Adrenal Gland Pheochromocytoma
  • Gastrointestinal Neuroendocrine Tumors
  • Paraganglioma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Clinical Trial Evaluating the Safety of Combining Lutathera(R) and Azedra(R) to Treat Mid-gut Neuroendocrine Tumors
  • Official Title: A Phase 1/2 Trial Using AZEDRA and LUTATHERA in a Dosimetrically-determined Optimal Combination for Therapy of Selected Patients With Midgut Neuroendocrine Tumors

Clinical Trial IDs

  • ORG STUDY ID: 202005556
  • SECONDARY ID: P50CA174521
  • NCT ID: NCT04614766

Conditions

  • Gastro-enteropancreatic Neuroendocrine Tumor
  • Neuroendocrine Tumors

Interventions

DrugSynonymsArms
Lutatheralutetium Lu 177 dotatateCombination Therapy
Azedraiobenguane I-131Combination Therapy

Purpose

This study is designed to identify the best tolerated doses of Lutathera® and Azedra® when co-administered to treat midgut neuroendocrine tumors. These drugs are radioactive drugs, known as radionuclide therapy, and are both approved in the treatment of midgut neuroendocrine tumor as single agents (not together). Currently, the safest and best tolerated doses of these drugs (when combined) is unknown. That is the purpose of this clinical trial.

Detailed Description

      Azedra and Lutatheraare are FDA-approved radioactive drugs designed to treat specific tumor
      cells. These drugs are a combination of the radiation (131-Iodine, 177-lutetium) and a
      protein that targets the tumor cell (MIBG or DOTATATE). Because these proteins are attracted
      to, and stick to, the tumor, the radiation is centered in the tumors. This kills more tumor
      cells and minimizes radiation-damage to healthy tissues, like the heart and lungs.

      Two organs still absorb some of the radiation, though: bone marrow and the kidney. These
      organs limit how much radiation can be given to tumors, but we don't know how much radiation
      is too much. Too much radiation to bone marrow can result in anemia. Too much radiation to
      the kidneys can result in kidney failure. From prior radiation therapies, we have a general
      idea of how much radiation we can give safely.

      Azedra and Lutathera have never been given together. We want to give them together because
      many times, tumors are actually groups of different types of cells. This means, not all the
      cells respond to therapy the same way. If some tumor cells survive therapy, the tumor will
      continue to grow and eventually come back. We know some mid-gut neuroendocrine tumors (NETs)
      have targets for DOTATATE and some other mid-gut NETs have targets for MIBG. We also have now
      identified that some people with mid-gut NETs have different tumors: some with targets for
      MIBG and some with targets for DOTATATE. For these people, this means treating only with
      Azedra or Lutathera will not be enough to treat their cancer. They need both radioactive
      drugs.

      Because we are combining these radioactive drugs, this study is known as a first-in-man
      study. We are also using a special imaging to help us estimate the radiation dose to the bone
      marrow and to the kidneys. This is what decides the final dose of Azedra and Lutathera.

      After receiving a standard treatment of Lutathera, participants are asked to undergo imaging
      to verify they have both MIBG and DOTATATE tumor types:

        -  participants are given a tracer dose of Azedra

        -  a special camera (SPECT/CT) collects images (scans)

        -  imaging (scans) are done over 4 calendar days

        -  blood samples are taken at that time, too, to measure the circulating amount of tracer
           doses

      If the scans show a participant does not have both MIBG and DOTATATE receptors, they continue
      with standard therapy (Lutathera only). Participants are asked to still undergo study
      assessments to provide a comparison group.

      If the scans show a participant has both MIBG and DOTATATE receptors, combined therapy is
      administered:

        -  a customized dose of Lutathera is given on day 1 of a treatment cycle. This is given
           outpatient.

        -  a customized dose of Azedra is given on day 2 of a treatment cycle. This is given
           inpatient (admitted to the hospital).

        -  participants are monitored through blood tests to identify the side effects of therapy.

      Each participant can have up to 2 cycles of therapy. The cycles are 12 weeks apart.

      The doses for Lutathera and Azedra are decided based on radiation to the bone marrow and
      radiation to the kidney. Doses are decided by how well other participants have done on this
      study.

      Participants have life long follow-up for this study. This is very important, because a study
      like this has not been done.
    

Trial Arms

NameTypeDescriptionInterventions
Combination TherapyExperimentalCombined treatment with Lutathera® and Azedra® Administered amounts of each drug are based on imaging and radiation dose constraints to the kidneys and the bone marrow. The drug administration is individualized to each participant.
  • Lutathera
  • Azedra
Lutathera® onlyActive ComparatorSingle agent Lutathera® administered per standard of care: 200 millicuries of drug every 8 weeks for a total of 4 doses.
  • Lutathera

Eligibility Criteria

        Inclusion Criteria:

          -  Ability to understand and willingness to provide informed consent; legally authorized
             representative will not be utilized compliant with the principles of good clinical
             practice (i.e., ICH E6(R2)).

          -  Stated willingness to comply with all study procedures and availability for duration
             of study

          -  Aged ≥ 18 years to 80 years at the time of study drug administration

          -  Pathologically confirmed (histology or cytology) malignant neoplasm that is determined
             to be:

               -  a well-differentiated neuroendocrine tumor (i.e. grade 1 or grade 2) with a
                  primary tumor location believed to be midgut, or,

               -  pheochromocytoma, or,

               -  paraganglioma

          -  Recommended to receive LUTATHERA® or AZEDRA® therapy

          -  Disease measuring ≥ 1.5 cm in diameter on CT or MRI as measured per RECIST

          -  Adequate performance status (ECOG of 0 or 1; or KPS of >70).

          -  Agrees to contraception during therapy.

          -  Agreement to adhere to Lifestyle Considerations throughout study duration

        Exclusion Criteria:

        An individual who meets any of the following criteria will be excluded from participation
        in this study:

          -  Patient with increased fall risk in the opinion of healthcare professionals

          -  Women who are pregnant.

          -  Women who are breast feeding.

          -  Surgery, radiation therapy, or chemotherapy ≤ 4 weeks of C1D1. (Toxicities from prior
             therapies should have resolved to ≤ CTCAE grade 1 or a new baseline established).

          -  Prior peptide-receptor radiotherapy (PRRT).

          -  Therapeutic investigational drug within 4 weeks of C1D1 (imaging agents are
             acceptable).

          -  A concurrent malignancy that, in the opinion of the investigator, would cause a safety
             risk by delaying therapy or confound/negatively impact study objectives (documentation
             of the rationale must be provided).

          -  History of congestive heart failure with a history of cardiac ejection fraction ≤ 35%.

          -  Patients unable to discontinue medications known to affect MIBG uptake (unless
             approved by the PI or designee)

          -  Proteinuria grade 2 (i.e., 2+ proteinuria).

          -  Prior external beam radiation dose of >16 Gy to the kidneys.

          -  Prior external beam radiation (including brachytherapy) involving 25% of the bone
             marrow (excluding scatter doses of 5 Gy) as estimated by a radiation oncologist.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to Octreoscan® or Netspot™.

        Participants meeting the above criteria will receive one cycle of standard Lutathera
        treatment (200 millicuries) as well as a tracer dose of Azedra for imaging. Participants
        will then undergo protocol specific imaging to calculate the radiation dose to the kidneys,
        the bone marrow, and to the tumor lesions.

        To continue on study and receive the combined therapy, a participant's imaging must
        demonstrate one of the following:

          -  At least one tumor that is positive for Azedra but negative for Lutathera in addition
             to Lutathera positive tumors, or,

          -  At least one tumor site where the calculated safe radiation dose to that tumor site is
             25% higher using the combined therapy compared to Lutathera alone

        Participants who do not meet this criteria are invited to participate in the comparator arm
        to receive standard Lutathera treatment as indicated by their physicians.
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1: Determination of maximum tolerated radiation dose (MTD) to the kidneys
Time Frame:9 months after initial treatment
Safety Issue:
Description:MTD will be determined by incidence of renal AEs as characterized by type, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.

Secondary Outcome Measures

Measure:Tumor size
Time Frame:6 months post-treatment
Safety Issue:
Description:Determine tumor size and response using RECIST 1.1 criteria in patients treated with the combined regimen
Measure:Tumor size
Time Frame:12 months post-treatment
Safety Issue:
Description:Determine tumor size and response using RECIST 1.1 criteria in patients treated with the combined regimen
Measure:Number of Treatment-Related Adverse Events
Time Frame:Up to 24 months post-treatment
Safety Issue:
Description:Categorize and quantify adverse events using the Common Terminology Criteria for Adverse Events (v5)

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:David Bushnell

Last Updated

October 28, 2020