177Lu-DTPA-Omburtamab Radioimmunotherapy for Leptomeningeal Metastasis From Solid Tumors (Breast, NSCLC, Malignant Melanoma)

NCT04315246 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 302
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 8

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.

Conditions

Leptomeningeal Metastasis; Solid Tumor, Adult

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events (AEs) and serious adverse events (SAEs)

  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

  1 year

• Incidence of AEs and SAEs

  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

  2 years

Secondary Outcomes (12)

• Maximum radioactivity count of lutetium-177 in blood

  2 weeks

• Elimination half-life of lutetium-177 radioactivity in blood

  2 weeks

• Absorbed radiation dose of lutetium-177 in blood and cerebrospinal fluid (CSF)

  2 weeks

• Dosimetry analysis of lutetium-177

  2 weeks

• Maximum Plasma Concentration [Cmax] in CSF

  7 weeks

Study Arms (1)

177Lu-DTPA-omburtamab

EXPERIMENTAL

Intracerebroventricular administration of 177Lu-DTPA-omburtamab for up to five cycles.

Biological: radiolabeled DPTA-omburtamab

Interventions

radiolabeled DPTA-omburtamab BIOLOGICAL

Biological, radiolabeled DPTA-omburtamab

Also known as: Drug: 177Lu-DTPA-omburtamab

177Lu-DTPA-omburtamab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Y-mAbs Therapeutics: lead

Study Sites (8)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

The University of Washington

Seattle, Washington, 98109, United States

Location

The Christie Hospital NHS Foundation Trust

Manchester, United Kingdom

Location

The Royal Marsden Hospital

Sutton, United Kingdom

Location

MeSH Terms

Conditions

Meningeal Carcinomatosis

Condition Hierarchy (Ancestors)

Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients will receive up to five cycles of intracerebroventricular 177Lu-DTPA-omburtamab. Safety and efficacy will be investigated during treatment and follow-up period.

Study Record Dates

• First Submitted: March 12, 2020
• First Posted: March 19, 2020
• Study Start: August 31, 2022
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: July 15, 2022

Record last verified: 2022-07

Locations

GB (2); US (6)