Leptomeningeal MetastasisPhase 1/2NCT04315246
177Lu-DTPA-Omburtamab Radioimmunotherapy for Leptomeningeal Metastasis From Solid Tumors (Breast, NSCLC, Malignant Melanoma)
A Phase 1/2 study testing radiolabeled DPTA-omburtamab in people with Leptomeningeal Metastasis and Solid Tumor, Adult, run by Y-mAbs Therapeutics at 8 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leptomeningeal Metastasis, Solid Tumor, Adult
- What is being tested?
- radiolabeled DPTA-omburtamab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 8 sitesin 2 countries
- Study dates
- 31 Aug 2022to 31 Dec 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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)
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
United States6 sites
Johns Hopkins
Baltimore, Maryland, 21287
Duke Cancer Center
Durham, North Carolina, 27710
M.D. Anderson Cancer Center
Houston, Texas, 77030
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
The University of Washington
Seattle, Washington, 98109
United Kingdom2 sites
The Christie Hospital NHS Foundation Trust
Manchester
The Royal Marsden Hospital
Sutton
About this study
Official title: A Phase I/II Trial of Intracerebroventricular 177Lu DTPA Omburtamab Radioimmunotherapy for Leptomeningeal Metastasis From Solid Tumors
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.
Read the 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).
- Conditions
- Leptomeningeal Metastasis, Solid Tumor, Adult
- Being tested
- radiolabeled DPTA-omburtamab
- Medical subject headings
- Meningeal Carcinomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
radiolabeled DPTA-omburtamabBiological
Also called Drug: 177Lu-DTPA-omburtamab
Biological, radiolabeled DPTA-omburtamab
| Study group | Role | What they receive |
|---|---|---|
| 177Lu-DTPA-omburtamab | Experimental | Intracerebroventricular administration of 177Lu-DTPA-omburtamab for up to five cycles. Receives: Biological: radiolabeled DPTA-omburtamab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 2 years
Secondary outcomes (12)
Maximum radioactivity count of lutetium-177 in blood
The time for maximum absorbed radiation dose
Measured: 2 weeks
Elimination half-life of lutetium-177 radioactivity in blood
The time for eliminating half of the radioactivity in blood
Measured: 2 weeks
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
Measured: 2 weeks
Dosimetry analysis of lutetium-177
Whole-body dosimetry by gamma camera scans and single-photon emission computed tomography (SPECT)
Measured: 2 weeks
Maximum Plasma Concentration [Cmax] in CSF
Concentration of 177Lu-DTPA-omburtamab in CSF
Measured: 7 weeks
Maximum Plasma Concentration [Cmax] in serum
Concentration of 177Lu-DTPA-omburtamab in serum
Measured: 7 weeks
Elimination Half Life in CSF
Concentration of 177Lu-DTPA-omburtamab in CSF
Measured: 7 weeks
Elimination Half Life in serum
Concentration of 177Lu-DTPA-omburtamab in serum
Measured: 7 weeks
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
Measured: 2 years
Investigator-assessed Duration of Response (DoR)
DoR is defined as the time from first response to LM progression
Measured: 2 years
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
Measured: 2 years
Overall Survival (OS)
OS is defined as the time from first treatment to date of death
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2020
- Study start31 Aug 2022 (estimated)
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Why it stopped: Business priorities
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leptomeningeal MetastasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Y-mAbs Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04315246
- Sponsor's protocol ID
- 302
- Status last verified
- Jul 2022
- First submitted
- 12 Mar 2020
- Last updated
- 15 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Trial of Intracerebroventricular 177Lu DTPA Omburtamab Radioimmunotherapy for Leptomeningeal Metastasis From Solid Tumors
- ClinicalTrials.gov ID
- NCT04315246
- Acronym / sponsor ID
- 302
- Conditions
- Leptomeningeal Metastasis, Solid Tumor, Adult
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Business priorities
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Y-mAbs TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 31 Aug 2022 (estimated)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 19 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| 177Lu-DTPA-omburtamab | Experimental | Biological: radiolabeled DPTA-omburtamabIntracerebroventricular administration of 177Lu-DTPA-omburtamab for up to five cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| radiolabeled DPTA-omburtamabAlso: Drug: 177Lu-DTPA-omburtamabBiological, radiolabeled DPTA-omburtamab | Biological | 177Lu-DTPA-omburtamab |
Primary outcome
Incidence of adverse events (AEs) and serious adverse events (SAEs)
Time frame: 1 year
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
Time frame: 2 years
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
12 secondary outcomes
Maximum radioactivity count of lutetium-177 in blood
Time frame: 2 weeks
Elimination half-life of lutetium-177 radioactivity in blood
Time frame: 2 weeks
Absorbed radiation dose of lutetium-177 in blood and cerebrospinal fluid (CSF)
Time frame: 2 weeks
Dosimetry analysis of lutetium-177
Time frame: 2 weeks
Maximum Plasma Concentration [Cmax] in CSF
Time frame: 7 weeks
Maximum Plasma Concentration [Cmax] in serum
Time frame: 7 weeks
Elimination Half Life in CSF
Time frame: 7 weeks
Elimination Half Life in serum
Time frame: 7 weeks
Response
Time frame: 2 years
Investigator-assessed Duration of Response (DoR)
Time frame: 2 years
Progression-free Survival (PFS)
Time frame: 2 years
Overall Survival (OS)
Time frame: 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing radiolabeled DPTA-omburtamab in people with Leptomeningeal Metastasis and Solid Tumor, Adult, run by Y-mAbs Therapeutics at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 15 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (AEs) and serious adverse events (SAEs) (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2022.