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Clinical Trial 20884

Cancer Type: Gastrointestinal Tumor
Study Type: Treatment
NCT#: NCT04234568

Phase: Phase I
Prinicipal Investigator: Strosberg, Jonathan

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Overview

Study Title

Phase I Trial of Triapine and Lutetium Lu 177 Dotatate in Combination for Well-Differentiated Somatostatin Receptor-Positive Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)

Summary

This phase I trial studies the side effects and best dose of triapine when given together with lutetium Lu 177 dotatate in treating patients with neuroendocrine tumors. Triapine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radioactive drugs, such as lutetium Lu 177 dotatate, may carry radiation directly to tumor cells and not harm normal cells. Giving triapine and lutetium Lu 177 dotatate together may be a good way in treating patients with neuroendocrine tumors.

Objective

Primary Objective: 1) To evaluate the safety & to determine the recommended phase 2 dose (RP2D) of Lutetium Lu 177 Dotatate in combination with triapine. 2) To observe and record anti-tumor activity. Although the clinical benefit of this combination has not yet been established, the intent of offering this treatment is to provide a possible therapeutic benefit, and thus the patient will be carefully monitored for tumor response and symptom relief in addition to safety and tolerability. 3) To determine the overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at 2, 4, 6, and 8 months post therapy. Secondary Objectives 1) To measure duration of response (DOR) associated with the combination. 2) To evaluate progression-free survival (PFS), 24-month PFS, and overall survival (OS). Correlative Objectives 1) Measure baseline gallium-dotatate biodistribution. 2) Evaluate oral triapine plasma pharmacokinetics and corresponding methemoglobin level by venous blood gas proportion. 3) Evaluate NETest at baseline and disease progression to correlate result with clinical outcome. 4) Describe the tumor molecular profile using whole exome sequencing (WES), as well as RNAseq by the National Clinical Laboratory Network (NCLN) Genomics Lab and correlate it with treatment outcome. 5) Collect plasma for circulating DNA (ctDNA) assessment.

Treatments

Therapies

Therapy (NOS)

Medications

Lutetium Lu 177 Dotatate (); Triapine ()

Inclusion Criteria

Inclusion Criteria:

  • Metastatic, histologically confirmed well-differentiated neuroendocrine tumor with positive dotatate scan (Gallium-68 or Copper-64) within 6 months. Lesions on gallium 68 dotatate scan will be considered positive if the maximum standard uptake value (SUVmax) is > 2 times SUV mean of normal liver parenchyma
  • Failure of at least one prior systemic cancer treatment, including somatostatin analogs
  • Patients must have progressive disease based on RECIST criteria, version 1.1 evidenced with computed tomography (CT) scans/magnetic resonance imaging (MRI) obtained within 24 months from enrollment
  • Patients must have measurable disease per RECIST 1.1
  • No prior exposure to peptide receptor radionuclide therapy
  • Recovered from adverse events of previously administered therapeutic agents to grade 1 or less toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
  • Archival tissue no longer than 6 months old should be present, otherwise baseline research biopsy is needed for WES
  • Eastern Cooperative Oncology Group (ECOG) performance status 0,1, or 2 (Karnofsky >= 60%)
  • Adequate organ and bone marrow function as outlined per protocol.
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen, in the opinion of the enrolling physician, are eligible for this trial
  • Pregnancy precaution: Men and women should avoid pregnancy for seven months after the date of their last treatment with lutetium Lu 177 dotatate.
  • Additional criteria may apply

  • Exclusion Criteria

    Exclusion Criteria:

  • Patients who have had major surgical procedures in the prior 6 weeks
  • Patients with an inability to swallow oral medications or gastrointestinal disease limiting absorption of oral agents
  • Patients who have received prior external beam radiotherapy to more than 50% of bone marrow, as determined by a radiation medicine physicist who will calculate the volume of bone marrow exposure in prior radiotherapy portals divided by the volume of total bone marrow harboring tissues. This ratio must be less than 50 percent
  • Uncontrolled congestive heart failure (New York Heart Association [NYHA] III, IV)
  • Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study
  • Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
  • Patients who are receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to triapine or lutetium Lu 177 dotatate
  • Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection; symptomatic decompensated congestive heart failure; unstable angina pectoris; cardiac arrhythmia; and known inadequately controlled hypertension
  • Patients with psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because triapine is a ribonucleotide reductase (RNR) inhibitor and lutetium Lu 177 dotatate is a peptide receptor radionuclide therapy with the potential for 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 triapine and lutetium Lu 177 dotatate, breastfeeding should be discontinued if the mother is treated with triapine and lutetium Lu 177 dotatate and for 2.5 months following the last treatment
  • Discontinue long-acting somatostatin analogs (e.g., long-acting octreotide) for at least 4 weeks prior to initiating lutetium Lu 177 dotatate. Long-acting somatostatin analog will be allowed to continue if patient has history of carcinoid syndrome and requires long-acting somatostatin analog for control of his/her functional syndrome

  • If you are interested in learning more about clinical trials, our clinical trial navigators can discuss your options and recommend opportunities that may be suitable for you. Call 813-745-6100 or 1-800-679-0775 (toll-free) or submit a clinical trials inquiry form.