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

Solid Tumor, Adult Clinical Trial

Official title:

A Phase I/II Trial of Intracerebroventricular 177Lu DTPA Omburtamab Radioimmunotherapy for Leptomeningeal Metastasis From Solid Tumors

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04315246
• Other study ID #: 302
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: August 31, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: July 2022
• Source: Y-mAbs Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Leptomeningeal Metastasis
• Meningeal Carcinomatosis
• Neoplasm Metastasis
• Solid Tumor, Adult

Intervention

Biological:
• radiolabeled DPTA-omburtamab
Biological, radiolabeled DPTA-omburtamab

Locations

Country	Name	City	State
United Kingdom	The Christie Hospital NHS Foundation Trust	Manchester
United Kingdom	The Royal Marsden Hospital	Sutton
United States	Johns Hopkins	Baltimore	Maryland
United States	Duke Cancer Center	Durham	North Carolina
United States	M.D. Anderson Cancer Center	Houston	Texas
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	The University of Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Y-mAbs Therapeutics

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

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