Description:
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.
Title
- Brief Title: 177Lu-DTPA-Omburtamab Radioimmunotherapy for Leptomeningeal Metastasis From Solid Tumors
- Official Title: A Phase I/II Trial of Intracerebroventricular 177Lu DTPA Omburtamab Radioimmunotherapy for Leptomeningeal Metastasis From Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
302
- NCT ID:
NCT04315246
Conditions
- Leptomeningeal Metastasis
- Solid Tumor, Adult
Interventions
| Drug | Synonyms | Arms |
|---|
| radiolabeled DPTA-omburtamab | Drug: 177Lu-DTPA-omburtamab | 177Lu-DTPA-omburtamab |
Purpose
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).
Trial Arms
| Name | Type | Description | Interventions |
|---|
| 177Lu-DTPA-omburtamab | Experimental | Intracerebroventricular administration of 177Lu-DTPA-omburtamab for up to five cycles. | - radiolabeled DPTA-omburtamab
|
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
- Smallest diameter of treated or untreated nodular or linear leptomeningeal metastasis
>0.5 cm on MRI (Part 2 only)
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Incidence of adverse events (AEs) and serious adverse events (SAEs) |
| Time Frame: | 1 year |
| Safety Issue: | |
| Description: | 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 |
Secondary Outcome Measures
| Measure: | Maximum radioactivity count of lutetium-177 in blood |
| Time Frame: | 2 weeks |
| Safety Issue: | |
| Description: | The time for maximum absorbed radiation dose |
| Measure: | Elimination half-life of lutetium-177 radioactivity in blood |
| Time Frame: | 2 weeks |
| Safety Issue: | |
| Description: | The time for eliminating half of the radioactivity in blood |
| Measure: | Absorbed radiation dose of lutetium-177 in blood and cerebrospinal fluid (CSF) |
| Time Frame: | 2 weeks |
| Safety Issue: | |
| Description: | Time-activity curves of radioactivity measurements in blood and CSF will be modeled to deliver absorbed doses in blood and CSF |
| Measure: | Dosimetry analysis of lutetium-177 |
| Time Frame: | 2 weeks |
| Safety Issue: | |
| Description: | Whole-body dosimetry by gamma camera scans and single-photon emission computed tomography (SPECT) |
| Measure: | Maximum Plasma Concentration [Cmax] in CSF |
| Time Frame: | 7 weeks |
| Safety Issue: | |
| Description: | Concentration of 177Lu-DTPA-omburtamab in CSF |
| Measure: | Maximum Plasma Concentration [Cmax] in serum |
| Time Frame: | 7 weeks |
| Safety Issue: | |
| Description: | Concentration of 177Lu-DTPA-omburtamab in serum |
| Measure: | Elimination Half Life in CSF |
| Time Frame: | 7 weeks |
| Safety Issue: | |
| Description: | Concentration of 177Lu-DTPA-omburtamab in CSF |
| Measure: | Elimination Half Life in serum |
| Time Frame: | 7 weeks |
| Safety Issue: | |
| Description: | Concentration of 177Lu-DTPA-omburtamab in serum |
| Measure: | Response |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Investigator-assessed Duration of Response (DoR) |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | DoR is defined as the time from first response to LM progression |
| Measure: | Progression-free Survival (PFS) |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | PFS is defined as the time from first treatment to date of LM progression or death from any cause, whichever comes first |
| Measure: | Overall Survival (OS) |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | OS is defined as the time from first treatment to date of death |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Not yet recruiting |
| Lead Sponsor: | Y-mAbs Therapeutics |
Last Updated
July 22, 2021
