Clinical Trials /

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

NCT03466216

Description:

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.

Related Conditions:
  • Neuroendocrine Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase 1 Study of AlphaMedix™ in Adult Subjects With SSTR (+) NET
  • Official Title: A Phase 1, Non-Randomized, Open-Label, Dose Escalation, Single-Center Study to Determine the Safety, Bio-distribution, and Preliminary Effectiveness of AlphaMedix™ in Adult Subjects With SSRT(+) NETs.

Clinical Trial IDs

  • ORG STUDY ID: ALPHAMEDIX01
  • NCT ID: NCT03466216

Conditions

  • Neuroendocrine Tumor

Interventions

DrugSynonymsArms
AlphaMedixAlphaMedix

Purpose

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.

Detailed Description

      This dose escalation study will include a maximum of 50 subjects with histologically
      confirmed NET, a positive somatostatin analogue scan, and no prior history of PRRT therapy.

      The study will begin with a single ascending dose (SAD) of AlphaMedix™ administered by IV.
      Subsequent cohorts will receive an incremental 30% increase that will continue until tumor
      response or DLT. Once tumor response is observed, the study will convert to a Multiple
      Ascending Dose (MAD) regimen. The MAD treatment regimen will start with the previous safe
      cohort's dose and will consist of 3 IV administrations of AlphaMedix™ at 8-week intervals.
      Subsequent cohorts will receive an incremental 30% increase that will continue until tumor
      response or DLT.

      The primary objective is to assess the safety and dose limiting toxicity (DLT) using
      ascending doses of AlphaMedix™. The secondary objectives are to determine the pharmacokinetic
      properties and preliminary effectiveness of AlphaMedix™.
    

Trial Arms

NameTypeDescriptionInterventions
AlphaMedixExperimentalThere is only a single treatment arm.
  • AlphaMedix

Eligibility Criteria

        Inclusion Criteria:

          -  ECOG status 0-2.

          -  Life expectancy of at least 12 weeks.

          -  Histologically confirmed diagnosis of SSTR (+) NET, unresectable or metastatic.

          -  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).

          -  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.

          -  SSTR(+) disease, as evidenced by available FDA approved SSTR imaging (SRI) within 4
             weeks prior to the first cycle.

          -  All FDA-approved therapies for which the subject is eligible have been exhausted.

          -  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)

        Exclusion Criteria:

          -  Prior whole-body radiotherapy and PRRT using 177Lu/90Y/111In- DOTATATE/DOTATOC or TAT

          -  Known hypersensitivity to 68Gallium, Octreotate, or any of the excipients of
             68Ga-DOTATATE, AA infusion or AlphaMedix™.

          -  Therapeutic use of any somatostatin analogue, including Sandostatin® LAR (within 28
             days) and Sandostatin® (within 1 day) prior to administration of investigational drug.

          -  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).

          -  Any subject who is taking concomitant medications that decrease renal function (such
             as aminoglycoside antibiotics).

          -  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.

          -  Current somatic or psychiatric disease/condition that may interfere with the
             objectives and assessments of the study.

          -  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,

          -  Uncontrolled congestive heart failure; subjects suspected of having this condition
             need to show ejection fraction of >55% as determined by multigated acquisition (MUGA)
             scan.

          -  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)

          -  GFR < 35 mL/min
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To determine dose-limiting toxicity (DLT)
Time Frame:8 weeks
Safety Issue:
Description:DLT is defined as non-hematological toxicity - all Grade 4 and Grade 3 (except alk. phos.) that is not responsive to NMT 72 hours of supportive care - and all hematological toxicity that does not recover to NMT than Grade 2 within 8 wks of dose administration.

Secondary Outcome Measures

Measure:Partial or complete response assessed by modified RECIST v1.1
Time Frame:8 weeks after injection
Safety Issue:
Description:CT/MRI or 18FDG-PET/CT (for patients who are FDG-avid at baseline) will be used to measure tumor size
Measure:To determine effective blood clearance and cumulative blood activity of 212-Pb
Time Frame:24 hours
Safety Issue:
Description:Blood will be taken at Time 0, 1 hr, 4 hr and 24 hr post-injection and measured for activity in an auto gamma counter
Measure:To determine the rate and extent of 212-Pb elimination in urine
Time Frame:24 hours
Safety Issue:
Description:Bladder will be emptied just prior to injection and qualitative urine collections will be done 0-1 hr, 1-4 hr and 4-24 hr post-injection and measured for activity in an auto gamma counter
Measure:Incidence of treatment-related AEs and SAEs as assessed by CTCAE v. 4
Time Frame:12 months
Safety Issue:
Description:AEs will be recorded both spontaneously by the patient and at all safety follow ups (2 wks, 4 wks, 6 wks, 8 wks post each injection and 3 mo, 6 mo, and 10 mo post last injection)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Radiomedix, Inc.

Trial Keywords

  • somatostatin receptor

Last Updated

March 8, 2018