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

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ClinicalTrials.gov Identifier: NCT04315246
Recruitment Status : Recruiting
First Posted : March 19, 2020
Last Update Posted : October 26, 2021
Sponsor:
Information provided by (Responsible Party):
Y-mAbs Therapeutics

Tracking Information
First Submitted Date  ICMJE March 12, 2020
First Posted Date  ICMJE March 19, 2020
Last Update Posted Date October 26, 2021
Estimated Study Start Date  ICMJE November 30, 2021
Estimated Primary Completion Date December 31, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 16, 2020)
  • Incidence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: 1 year ]
    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
  • Incidence of AEs and SAEs [ Time Frame: 2 years ]
    In Part 2, safety will be evaluated by the incidence of AEs and SAEs graded according to CTCAE version 5.0, at the RP2D defined in Part 1
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 16, 2020)
  • Maximum radioactivity count of lutetium-177 in blood [ Time Frame: 2 weeks ]
    The time for maximum absorbed radiation dose
  • Elimination half-life of lutetium-177 radioactivity in blood [ Time Frame: 2 weeks ]
    The time for eliminating half of the radioactivity in blood
  • Absorbed radiation dose of lutetium-177 in blood and cerebrospinal fluid (CSF) [ Time Frame: 2 weeks ]
    Time-activity curves of radioactivity measurements in blood and CSF will be modeled to deliver absorbed doses in blood and CSF
  • Dosimetry analysis of lutetium-177 [ Time Frame: 2 weeks ]
    Whole-body dosimetry by gamma camera scans and single-photon emission computed tomography (SPECT)
  • Maximum Plasma Concentration [Cmax] in CSF [ Time Frame: 7 weeks ]
    Concentration of 177Lu-DTPA-omburtamab in CSF
  • Maximum Plasma Concentration [Cmax] in serum [ Time Frame: 7 weeks ]
    Concentration of 177Lu-DTPA-omburtamab in serum
  • Elimination Half Life in CSF [ Time Frame: 7 weeks ]
    Concentration of 177Lu-DTPA-omburtamab in CSF
  • Elimination Half Life in serum [ Time Frame: 7 weeks ]
    Concentration of 177Lu-DTPA-omburtamab in serum
  • Response [ Time Frame: 2 years ]
    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
  • Investigator-assessed Duration of Response (DoR) [ Time Frame: 2 years ]
    DoR is defined as the time from first response to LM progression
  • Progression-free Survival (PFS) [ Time Frame: 2 years ]
    PFS is defined as the time from first treatment to date of LM progression or death from any cause, whichever comes first
  • Overall Survival (OS) [ Time Frame: 2 years ]
    OS is defined as the time from first treatment to date of death
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 177Lu-DTPA-Omburtamab Radioimmunotherapy for Leptomeningeal Metastasis From Solid Tumors
Official Title  ICMJE A Phase I/II Trial of Intracerebroventricular 177Lu DTPA Omburtamab Radioimmunotherapy for Leptomeningeal Metastasis From Solid Tumors
Brief Summary 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 5 cycles, 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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Patients will receive up to five cycles of intracerebroventricular 177Lu-DTPA-omburtamab. Safety and efficacy will be investigated during treatment and follow-up period.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Leptomeningeal Metastasis
  • Solid Tumor, Adult
Intervention  ICMJE Biological: radiolabeled DPTA-omburtamab
Biological, radiolabeled DPTA-omburtamab
Other Name: Drug: 177Lu-DTPA-omburtamab
Study Arms  ICMJE Experimental: 177Lu-DTPA-omburtamab
Intracerebroventricular administration of 177Lu-DTPA-omburtamab for up to five cycles.
Intervention: Biological: radiolabeled DPTA-omburtamab
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 16, 2020)
63
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2024
Estimated Primary Completion Date December 31, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • Presence of an intracerebroventricular access device before first dosing

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
  • Unacceptable coagulation function prior to first dosing defined as INR Grade 2 or above
  • 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
  • Other significant disease or condition that in the investigator's opinion would exclude the patient from the trial.
  • Smallest diameter of treated or untreated nodular or linear leptomeningeal metastasis >0.5 cm on MRI (Part 2 only)
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: Joris Wilms +4570261414 clinicaltrials@ymabs.com
Listed Location Countries  ICMJE United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04315246
Other Study ID Numbers  ICMJE 302
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 Y-mAbs Therapeutics
Study Sponsor  ICMJE Y-mAbs Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Y-mAbs Therapeutics
Verification Date October 2021

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