Clinical trial NCT04315246: 177Lu-DTPA-Omburtamab Radioimmunotherapy for Leptomeningeal Metastasis From Solid Tumors (Breast, NSCLC, Malignant Melanoma)
Official title: A Phase I/II Trial of Intracerebroventricular 177Lu DTPA Omburtamab Radioimmunotherapy for Leptomeningeal Metastasis From Solid Tumors
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Leptomeningeal Metastasis
Solid Tumor, Adult
Lead sponsor: Y-mAbs Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-03-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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).

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
* 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)

Primary outcomes:
measure: Incidence of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 1 year
measure: Incidence of AEs and SAEs
timeFrame: 2 years
Secondary outcomes:
measure: Maximum radioactivity count of lutetium-177 in blood
timeFrame: 2 weeks
measure: Elimination half-life of lutetium-177 radioactivity in blood
timeFrame: 2 weeks
measure: Absorbed radiation dose of lutetium-177 in blood and cerebrospinal fluid (CSF)
timeFrame: 2 weeks
measure: Dosimetry analysis of lutetium-177
timeFrame: 2 weeks
measure: Maximum Plasma Concentration [Cmax] in CSF
timeFrame: 7 weeks
measure: Maximum Plasma Concentration [Cmax] in serum
timeFrame: 7 weeks
measure: Elimination Half Life in CSF
timeFrame: 7 weeks
measure: Elimination Half Life in serum
timeFrame: 7 weeks
measure: Response
timeFrame: 2 years
measure: Investigator-assessed Duration of Response (DoR)
timeFrame: 2 years
measure: Progression-free Survival (PFS)
timeFrame: 2 years
measure: Overall Survival (OS)
timeFrame: 2 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Houston
country: United States
facility: M.D. Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: The University of Washington
state: Washington
city: Manchester
country: United Kingdom
facility: The Christie Hospital NHS Foundation Trust
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital
Study officials:
References: