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.
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
Drug | Synonyms | Arms |
---|
Lutathera | lutetium Lu 177 dotatate | Combination Therapy |
Azedra | iobenguane I-131 | Combination 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
Name | Type | Description | Interventions |
---|
Combination Therapy | Experimental | Combined 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® only | Active Comparator | Single agent Lutathera® administered per standard of care: 200 millicuries of drug every 8 weeks for a total of 4 doses. | |
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
March 30, 2021