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

Primary Purpose

Leptomeningeal Metastasis, Solid Tumor, Adult

Status
Withdrawn
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
radiolabeled DPTA-omburtamab
Sponsored by
Y-mAbs Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leptomeningeal Metastasis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Cedars-Sinai Medical Center
  • Johns Hopkins
  • Memorial Sloan Kettering Cancer Center
  • Duke Cancer Center
  • M.D. Anderson Cancer Center
  • The University of Washington
  • The Christie Hospital NHS Foundation Trust
  • The Royal Marsden Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

177Lu-DTPA-omburtamab

Arm Description

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

Outcomes

Primary Outcome Measures

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
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

Secondary Outcome Measures

Maximum radioactivity count of lutetium-177 in blood
The time for maximum absorbed radiation dose
Elimination half-life of lutetium-177 radioactivity in blood
The time for eliminating half of the radioactivity in blood
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
Dosimetry analysis of lutetium-177
Whole-body dosimetry by gamma camera scans and single-photon emission computed tomography (SPECT)
Maximum Plasma Concentration [Cmax] in CSF
Concentration of 177Lu-DTPA-omburtamab in CSF
Maximum Plasma Concentration [Cmax] in serum
Concentration of 177Lu-DTPA-omburtamab in serum
Elimination Half Life in CSF
Concentration of 177Lu-DTPA-omburtamab in CSF
Elimination Half Life in serum
Concentration of 177Lu-DTPA-omburtamab in serum
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
Investigator-assessed Duration of Response (DoR)
DoR is defined as the time from first response to LM progression
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
Overall Survival (OS)
OS is defined as the time from first treatment to date of death

Full Information

First Posted
March 12, 2020
Last Updated
July 12, 2022
Sponsor
Y-mAbs Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT04315246
Brief Title
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

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Withdrawn
Why Stopped
Business priorities
Study Start Date
August 31, 2022 (Anticipated)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Y-mAbs Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leptomeningeal Metastasis, Solid Tumor, Adult

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
177Lu-DTPA-omburtamab
Arm Type
Experimental
Arm Description
Intracerebroventricular administration of 177Lu-DTPA-omburtamab for up to five cycles.
Intervention Type
Biological
Intervention Name(s)
radiolabeled DPTA-omburtamab
Other Intervention Name(s)
Drug: 177Lu-DTPA-omburtamab
Intervention Description
Biological, radiolabeled DPTA-omburtamab
Primary Outcome Measure Information:
Title
Incidence of adverse events (AEs) and serious adverse events (SAEs)
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
Time Frame
1 year
Title
Incidence of AEs and SAEs
Description
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
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Maximum radioactivity count of lutetium-177 in blood
Description
The time for maximum absorbed radiation dose
Time Frame
2 weeks
Title
Elimination half-life of lutetium-177 radioactivity in blood
Description
The time for eliminating half of the radioactivity in blood
Time Frame
2 weeks
Title
Absorbed radiation dose of lutetium-177 in blood and cerebrospinal fluid (CSF)
Description
Time-activity curves of radioactivity measurements in blood and CSF will be modeled to deliver absorbed doses in blood and CSF
Time Frame
2 weeks
Title
Dosimetry analysis of lutetium-177
Description
Whole-body dosimetry by gamma camera scans and single-photon emission computed tomography (SPECT)
Time Frame
2 weeks
Title
Maximum Plasma Concentration [Cmax] in CSF
Description
Concentration of 177Lu-DTPA-omburtamab in CSF
Time Frame
7 weeks
Title
Maximum Plasma Concentration [Cmax] in serum
Description
Concentration of 177Lu-DTPA-omburtamab in serum
Time Frame
7 weeks
Title
Elimination Half Life in CSF
Description
Concentration of 177Lu-DTPA-omburtamab in CSF
Time Frame
7 weeks
Title
Elimination Half Life in serum
Description
Concentration of 177Lu-DTPA-omburtamab in serum
Time Frame
7 weeks
Title
Response
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
Time Frame
2 years
Title
Investigator-assessed Duration of Response (DoR)
Description
DoR is defined as the time from first response to LM progression
Time Frame
2 years
Title
Progression-free Survival (PFS)
Description
PFS is defined as the time from first treatment to date of LM progression or death from any cause, whichever comes first
Time Frame
2 years
Title
Overall Survival (OS)
Description
OS is defined as the time from first treatment to date of death
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Facility Information:
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Duke Cancer Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
M.D. Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
The University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
The Christie Hospital NHS Foundation Trust
City
Manchester
Country
United Kingdom
Facility Name
The Royal Marsden Hospital
City
Sutton
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

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

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