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

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ClinicalTrials.gov Identifier: NCT04315246
Recruitment Status : Not yet recruiting
First Posted : March 19, 2020
Last Update Posted : March 19, 2020
Sponsor:
Information provided by (Responsible Party):
Y-mAbs Therapeutics

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.

Condition or disease Intervention/treatment Phase
Leptomeningeal Metastasis Solid Tumor, Adult Biological: radiolabeled DPTA-omburtamab Phase 1 Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 63 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Patients will receive up to five cycles in Part 1 and up to 104 weeks in Part 2 of intracerebroventricular 177Lu-DTPA-omburtamab. Safety and efficacy will be investigated during treatment and follow-up period.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of Intracerebroventricular 177Lu DTPA Omburtamab Radioimmunotherapy for Leptomeningeal Metastasis From Solid Tumors
Estimated Study Start Date : October 31, 2020
Estimated Primary Completion Date : October 31, 2024
Estimated Study Completion Date : October 31, 2024

Arm Intervention/treatment
Experimental: 177Lu-DTPA-omburtamab
Intracerebroventricular administration of 177Lu-DTPA-omburtamab for up to five cycles (Part 1) and up to 104 weeks (Part 2).
Biological: radiolabeled DPTA-omburtamab
Biological, radiolabeled DPTA-omburtamab
Other Name: Drug: 177Lu-DTPA-omburtamab




Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. Maximum radioactivity count of lutetium-177 in blood [ Time Frame: 2 weeks ]
    The time for maximum absorbed radiation dose

  2. Elimination half-life of lutetium-177 radioactivity in blood [ Time Frame: 2 weeks ]
    The time for eliminating half of the radioactivity in blood

  3. 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

  4. Dosimetry analysis of lutetium-177 [ Time Frame: 2 weeks ]
    Whole-body dosimetry by gamma camera scans and single-photon emission computed tomography (SPECT)

  5. Maximum Plasma Concentration [Cmax] in CSF [ Time Frame: 7 weeks ]
    Concentration of 177Lu-DTPA-omburtamab in CSF

  6. Maximum Plasma Concentration [Cmax] in serum [ Time Frame: 7 weeks ]
    Concentration of 177Lu-DTPA-omburtamab in serum

  7. Elimination Half Life in CSF [ Time Frame: 7 weeks ]
    Concentration of 177Lu-DTPA-omburtamab in CSF

  8. Elimination Half Life in serum [ Time Frame: 7 weeks ]
    Concentration of 177Lu-DTPA-omburtamab in serum

  9. 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

  10. Investigator-assessed Duration of Response (DoR) [ Time Frame: 2 years ]
    DoR is defined as the time from first response to LM progression

  11. 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

  12. Overall Survival (OS) [ Time Frame: 2 years ]
    OS is defined as the time from first treatment to date of death



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04315246


Contacts
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Contact: Joris Wilms +4570261414 clinicaltrials@ymabs.com

Sponsors and Collaborators
Y-mAbs Therapeutics

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Responsible Party: Y-mAbs Therapeutics
ClinicalTrials.gov Identifier: NCT04315246    
Other Study ID Numbers: 302
First Posted: March 19, 2020    Key Record Dates
Last Update Posted: March 19, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasm Metastasis
Meningeal Carcinomatosis
Neoplasms
Neoplastic Processes
Pathologic Processes
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases