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

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ClinicalTrials.gov Identifier: NCT03466216
Recruitment Status : Completed
First Posted : March 15, 2018
Last Update Posted : July 12, 2021
Sponsor:
Collaborator:
Orano Med LLC
Information provided by (Responsible Party):
Radiomedix, Inc.

Tracking Information
First Submitted Date  ICMJE January 11, 2018
First Posted Date  ICMJE March 15, 2018
Last Update Posted Date July 12, 2021
Actual Study Start Date  ICMJE February 5, 2018
Actual Primary Completion Date July 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 8, 2018)
  • To determine dose-limiting toxicity (DLT) [ Time Frame: 8 weeks ]
    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.
  • To determine the maximum tolerated dose (MTD) [ Time Frame: 8 weeks ]
    The MTD is the dose level below that which 2 out of 6 subjects in a cohort have DLT.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 8, 2018)
  • Partial or complete response assessed by modified RECIST v1.1 [ Time Frame: 8 weeks after injection ]
    CT/MRI or 18FDG-PET/CT (for patients who are FDG-avid at baseline) will be used to measure tumor size
  • To determine effective blood clearance and cumulative blood activity of 212-Pb [ Time Frame: 24 hours ]
    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
  • To determine the rate and extent of 212-Pb elimination in urine [ Time Frame: 24 hours ]
    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
  • Incidence of treatment-related AEs and SAEs as assessed by CTCAE v. 4 [ Time Frame: 12 months ]
    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)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1 Study of AlphaMedix™ in Adult Subjects With SSTR (+) NET
Official Title  ICMJE 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.
Brief Summary

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™.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neuroendocrine Tumor
Intervention  ICMJE Drug: AlphaMedix
There is only a single treatment intervention.
Study Arms  ICMJE Experimental: AlphaMedix
There is only a single treatment arm.
Intervention: Drug: AlphaMedix
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 9, 2021)
33
Original Estimated Enrollment  ICMJE
 (submitted: March 8, 2018)
50
Actual Study Completion Date  ICMJE July 1, 2021
Actual Primary Completion Date July 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03466216
Other Study ID Numbers  ICMJE ALPHAMEDIX01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Radiomedix, Inc.
Study Sponsor  ICMJE Radiomedix, Inc.
Collaborators  ICMJE Orano Med LLC
Investigators  ICMJE
Principal Investigator: Rodolfo Nunez, MD Excel Diagnostics and Nuclear Oncology Center
PRS Account Radiomedix, Inc.
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP