Azedra and Lutathera for the Treatment of Neuroendocrine Tumors
This phase I/II trial studies the effect of Azedra and Lutathera in treating patients with neuroendocrine tumors. Azedra (which uses radioactive iodine) and Lutathera (which uses the radioactive element lutetium) are radioactive drugs to treat neuroendocrine tumors. Many neuroendocrine tumors have receptors on their cells for both of these radioactive drugs to target. In order to kill as many tumor cells as possible, the radioactive drugs must target as many of these receptors as possible. Giving Azedra and Lutathera together may kill more tumor cells in patients with neuroendocrine tumors.
Inclusion Criteria
- STEP 1 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 or intermediate grade neuroendocrine tumor (i.e. grade 1 or grade 2) with a primary tumor location believed to be foregut, midgut, or hindgut
- Recommended to receive Lutathera or Azedra therapy
- Disease measuring >= 1.5 cm in diameter on computed tomography (CT) or magnetic resonance imaging (MRI) as measured per RECIST
- Adequate performance status (Eastern Cooperative Oncology Group [ECOG] of 0 or 1; or Karnofsky performance status [KPS] of > 70)
- Agrees to contraception during therapy
- Agreement to adhere to lifestyle considerations throughout study duration
- STEP 2 INCLUSION CRITERIA:
- One or more MIBG+ and edotreotide (DOTATOC)‐ tumors in addition to one or more DOTATOC+ tumors
- One or more tumor sites where the calculated "safe" radiation tumor dose is higher by at least 25% with a combination of Azedra and Lutathera than it is with Lutathera alone
Exclusion Criteria
- STEP 1 EXCLUSION CRITERIA
- Eligible for curative surgical resection
- 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 cycle (C)1 day (D)1. (Toxicities from prior therapies should have resolved to =< Common Terminology Criteria for Adverse Events [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 iobenguane (MIBG) uptake (unless approved by the principal investigator [PI] or designee)
- Proteinuria grade 2 (i.e., >= 2+ proteinuria)
- Prior external beam to the kidneys unless approved by the principal investigator
- 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
Additional locations may be listed on ClinicalTrials.gov for NCT04614766.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated radiation dose for the kidneys and bone marrow in combined therapy with dosimetrically individualized levels of cold contaminant-free iobenguane I-131 (Azedra) and lutetium Lu 177 dotatate (Lutathera) in patients with low and intermediate grade midgut neuroendocrine tumors (NETs) who have progressive metastatic disease who are candidates for peptide receptor radionuclide therapy (PRRT).
II. Determine initial effect size utilizing objective response rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 complete response (CR)/partial response (PR) when employing the recommended phase 2 organ radiation dose constraints in a phase 2 clinical trial expansion.
SECONDARY OBJECTIVES:
I. Determine tumor size and response (as per RECIST 1.1) to treatment with dosimetrically optimized combinations of Azedra and Lutathera.
II. Evaluate and characterize adverse events, including hematologic and renal toxicities, associated with therapeutic administration of dosimetrically optimized combinations of Azedra and Lutathera.
EXPLORATORY OBJECTIVE:
I. Explore the patient experience using quality of life and patient‐reported symptoms for patients with neuroendocrine tumor when treated with combined Azedra and Lutathera.
OUTLINE: Patients are assigned to 1 of 2 cohorts.
COHORT I: Patients receive lutetium Lu 177 dotatate intravenously (IV) over 30-40 minutes and tracer dose of cold contaminant-free iobenguane I-131 on day 1 of cycle 1. Patients undergo a series of single photon emission computed tomography (SPECT)/computed tomography (CT) scans after first dose of lutetium Lu 177 dotatate. Patients then receive lutetium Lu 177 dotatate IV over 30-40 minutes and cold contaminant-free iobenguane I-131 IV over 30 minutes on day 1 every 10-12 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
COHORT II: Patients not eligible for the combinatorial therapy receive lutetium Lu 177 dotatate IV over 30-40 minutes and tracer dose of cold contaminant-free iobenguane I-131 on day 1 of cycle 1. Patients undergo a series of SPECT/CT scans after first dose of lutetium Lu 177 dotatate. Patients then receive lutetium Lu 177 dotatate IV over 30-40 minutes on day 1 every 10-12 weeks for up to 3 additional cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months.
Trial PhasePhase I/II
Trial Typetreatment
Lead OrganizationUniversity of Iowa/Holden Comprehensive Cancer Center
Principal InvestigatorDavid Bushnell
- Primary ID202005556
- Secondary IDsNCI-2020-11392
- ClinicalTrials.gov IDNCT04614766