Clinical Trials /

177Lu-DTPA-Omburtamab Radioimmunotherapy for Leptomeningeal Metastasis From Solid Tumors

NCT04315246

Description:

Adults with leptomeningeal metastasis from solid tumors will be treated with 177Lu-DTPA-omburtamab, which is a radioactive labelling of a murine monoclonal antibody targeting B7-H3.

Related Conditions:
  • Breast Ductal Carcinoma
  • Lobular Breast Carcinoma
  • Melanoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 177Lu-DTPA-Omburtamab Radioimmunotherapy for Leptomeningeal Metastasis From Solid Tumors
  • Official Title: A Phase I/II Trial of Intracerebroventricular 177Lu DTPA Omburtamab Radioimmunotherapy for Leptomeningeal Metastasis From Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 302
  • NCT ID: NCT04315246

Conditions

  • Leptomeningeal Metastasis
  • Solid Tumor, Adult

Interventions

DrugSynonymsArms
radiolabeled DPTA-omburtamabDrug: 177Lu-DTPA-omburtamab177Lu-DTPA-omburtamab

Purpose

Adults with leptomeningeal metastasis from solid tumors will be treated with 177Lu-DTPA-omburtamab, which is a radioactive labelling of a murine monoclonal antibody targeting B7-H3.

Detailed Description

      Part 1 is a dose-escalation phase with a 3+3 sequential-group design in which patients will
      receive a dosimetry dose followed by maximum of five 5-week cycles of treatment doses of
      intracerebroventricular 177Lu-DTPA-omburtamab.

      Part 2 is a cohort-expansion phase in which patients will receive a treatment at the
      recommended dose determined in Part 1, until confirmed LM progression, unacceptable toxicity,
      or for maximum of 104 weeks, whichever comes first; however, the total number of cycles will
      be determined based upon data from Part 1 (e.g., the dosimetry data) to minimize the risk of
      radiation necrosis and decreased neurological function End of treatment will take place
      within 5 weeks after the last cycle and thereafter the patients will be enter the follow-up
      period. The patients will be followed for up until one year after first dose (Part 1) and 2
      years after first dose (Part 2).
    

Trial Arms

NameTypeDescriptionInterventions
177Lu-DTPA-omburtamabExperimentalIntracerebroventricular administration of 177Lu-DTPA-omburtamab for up to five cycles (Part 1) and up to 104 weeks (Part 2).
  • radiolabeled DPTA-omburtamab

Eligibility Criteria

        Inclusion Criteria:

          -  Primary ductal or lobular breast cancer, non-small cell lung cancer, or malignant
             melanoma

          -  Type I or Type II LM with a "confirmed" or "probable" diagnosis according to EANO-ESMO
             guidelines 2017

          -  Life expectancy more than 2 months, as judged by the Investigator

          -  ECOG Performance status 0, 1, or 2

          -  Acceptable hematological status and liver and kidney function

          -  Written informed consent obtained in accordance with local regulations

        Exclusion Criteria:

          -  Obstructive or symptomatic communicating hydrocephalus

          -  Progressive systemic (extra-leptomeningeal) disease

          -  Uncontrolled life-threatening infection

          -  Ventriculo-peritoneal shunts without programmable valves. Ventriculo-atrial or
             ventriculo-pleural shunts

          -  Received craniospinal irradiation (for intraparenchymal or dural metastases) or
             intrathecal cytotoxic anti-cancer therapy less than 3 weeks prior to first dose of
             177Lu-DTPA-omburtamab

          -  Severe non-hematologic organ toxicity; specifically, any renal, cardiac, hepatic,
             pulmonary, or gastrointestinal system toxicity Grade 3 or above prior to enrolment

          -  Grade 4 nervous system disorder. Hearing loss or stable neurological deficits due to
             brain tumor are allowed

          -  Female of childbearing potential, who are pregnant, breast-feeding, intend to become
             pregnant, or are not using highly effective contraceptive methods or male who is not
             using highly effective contraceptive method

          -  Smallest diameter of treated or untreated nodular or linear leptomeningeal metastasis
             >0.5 cm on MRI (Part 2 only)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events (AEs) and serious adverse events (SAEs)
Time Frame:1 year
Safety Issue:
Description:Safety will be evaluated by the incidence of AEs and SAEs graded according to CTCAE version 5.0. The maximum tolerated dose and the recommended phase 2 dose (RP2D) will be determined in Part 1

Secondary Outcome Measures

Measure:Maximum radioactivity count of lutetium-177 in blood
Time Frame:2 weeks
Safety Issue:
Description:The time for maximum absorbed radiation dose
Measure:Elimination half-life of lutetium-177 radioactivity in blood
Time Frame:2 weeks
Safety Issue:
Description:The time for eliminating half of the radioactivity in blood
Measure:Absorbed radiation dose of lutetium-177 in blood and cerebrospinal fluid (CSF)
Time Frame:2 weeks
Safety Issue:
Description:Time-activity curves of radioactivity measurements in blood and CSF will be modeled to deliver absorbed doses in blood and CSF
Measure:Dosimetry analysis of lutetium-177
Time Frame:2 weeks
Safety Issue:
Description:Whole-body dosimetry by gamma camera scans and single-photon emission computed tomography (SPECT)
Measure:Maximum Plasma Concentration [Cmax] in CSF
Time Frame:7 weeks
Safety Issue:
Description:Concentration of 177Lu-DTPA-omburtamab in CSF
Measure:Maximum Plasma Concentration [Cmax] in serum
Time Frame:7 weeks
Safety Issue:
Description:Concentration of 177Lu-DTPA-omburtamab in serum
Measure:Elimination Half Life in CSF
Time Frame:7 weeks
Safety Issue:
Description:Concentration of 177Lu-DTPA-omburtamab in CSF
Measure:Elimination Half Life in serum
Time Frame:7 weeks
Safety Issue:
Description:Concentration of 177Lu-DTPA-omburtamab in serum
Measure:Response
Time Frame:2 years
Safety Issue:
Description:Objective response rate (ORR) will be defined as the proportion of all evaluable patients achieving a response as the best overall response at the time of assessment
Measure:Investigator-assessed Duration of Response (DoR)
Time Frame:2 years
Safety Issue:
Description:DoR is defined as the time from first response to LM progression
Measure:Progression-free Survival (PFS)
Time Frame:2 years
Safety Issue:
Description:PFS is defined as the time from first treatment to date of LM progression or death from any cause, whichever comes first
Measure:Overall Survival (OS)
Time Frame:2 years
Safety Issue:
Description:OS is defined as the time from first treatment to date of death

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Y-mAbs Therapeutics

Last Updated

October 2, 2020