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Oranomed

Clinical Trial · NCT03466216

Phase 1 Study of AlphaMedix™ in Adult Subjects With SSTR (+) NET

Overview

AlphaMedix™ (²¹²Pb-DOTAMTATE) is a radiotherapeutic drug indicated in subjects with unresectable, metastatic somatostatin receptor (SSTR) positive neuroendocrine tumors (NETs). Because 212Pb is an in vivo generator of alpha particles, it is particularly suitable for SSTR therapy applications. This drug addresses an unmet need in the field of peptide receptor radionuclide therapy (PRRT) for NETs. Substitution of an alpha emitter (²¹²Pb) for the beta emitters currently being used (i.e., 177Lu or 90Y) will provide significantly higher Linear Energy Transfer (LET) and a shorter path length. Higher LET particles should cause more tumor cell death. Shorter path length should result in less collateral damage of the normal tissue and therefore less side effects for subjects receiving the drug.

Sponsor

Oranomed

Phase

Phase 1

ClinicalTrials.gov

NCT03466216

Drug / Compound

DOTAMTATE

Isotope(s):
Target(s):
  • SSTR2
Ligand Class: Peptides
Chelator: TCMC

Eligibility

Inclusion

  • Life expectancy of at least 12 weeks.
  • Histologically confirmed diagnosis of SSTR (+) NET, unresectable or metastatic.
  • ECOG status 0-2.
  • Measurable disease per RECIST 1.1 on CT/MRI scans, defined as at least 1 lesion with ≥ 1 cm in longest diameter (LD) (lymph nodes along short axis).
  • SSTR(+) disease, as evidenced by available FDA approved SSTR imaging (SRI) within 4 weeks prior to the first cycle.
  • Recent blood test results (within 2 weeks pre-dose) as follows: Sufficient bone marrow capacity as defined by white blood cell (WBC) ≥2,500/µl and WBC ≥2,000/µl for subsequent cycles; platelets ≥ 100,000/µl for the first treatment and ≥75,000 for the subsequent therapies, hemoglobin (HgB) ≥8.9 g/dl for the first treatment and 8.0 g/dl for the subsequent therapies, ANC ≥1,500/µl for the first treatment and ≥1,000/µl; for the subsequent therapies; ALT, AST values ≤3 times upper limit of normal (ULN); Bilirubin: ≤3 times ULN; Serum creatinine ≤150 µmol/liter or 1.7 mg/dl; Negative pregnancy test in women capable of child-bearing within 48 hours of administration; Serum albumin \> 3.0 g/L (\<3.0 g/L may be acceptable at the discretion of PI, if PT, PTT, and INR are within normal range)
  • All FDA-approved therapies for which the subject is eligible have been exhausted.
  • Appropriate diagnostic imaging studies, at the discretion of the PI including but not limited to CT, MRI, 18F-FDG PET/CT, NAF PET/CT bone scan, ultrasound, etc. of the tumor region or suspected area within the 4 weeks of dosing day.

Exclusion

  • GFR \< 35 mL/min
  • Indication for surgical lesion removal with curative potential
  • Known brain metastases; unless these metastases have been treated and stabilized 6 months prior to enrollment
  • Completion of: (1) cytotoxic chemotherapy for less than 6 weeks; (2) a biological agent for less than 5 half-lives; and (3) radiation therapy for less than 6 weeks prior to study enrolment,
  • Prior whole-body radiotherapy and PRRT using 177Lu/90Y/111In- DOTATATE/DOTATOC or TAT
  • Uncontrolled congestive heart failure; subjects suspected of having this condition need to show ejection fraction of \>55% as determined by multigated acquisition (MUGA) scan.
  • Any subject who is taking concomitant medications that decrease renal function (such as aminoglycoside antibiotics).
  • Therapeutic use of any somatostatin analogue, including Sandostatin® LAR (within 28 days) and Sandostatin® (within 1 day) prior to administration of investigational drug.
  • Carcinoid heart disease: Prior history of torsade de pointe, or congenital long QT syndrome; Conditions with screening ECG repolarization difficult to interpret, or showing significant abnormalities. This includes, but is not limited to: high degree AV block, pacemaker, atrial fibrillation or flutter; QTcF interval \> 480 msec on screening ECG; Significant hypokalemia at screening (Potassium \<3.5 mMol/L); Significant hypomagnesemia at screening (Mg++ \<0.7 mMol/L)
  • Current somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study.
  • Female subjects who are pregnant, lactating or women of childbearing potential not willing to practice effective contraceptive techniques during the study period and for 8 weeks post-injection or male subjects who have female partners of childbearing potential not willing to practice abstinence or effective contraception, during the study period and for 8 weeks post-injection.
  • Subjects with unusual hematological parameters, including an increased mean corpuscular volume (MCV) (\>100,000), and especially in those who had previous chemotherapy, the advice of a hematologist should be sought for adequate further work-up to rule out myelodysplastic syndrome (MDS).
  • Known hypersensitivity to 68Gallium, Octreotate, or any of the excipients of 68Ga-DOTATATE, AA infusion or AlphaMedix™.

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