Ignite Creation Date:
2025-12-24 @ 12:20 PM
Ignite Modification Date:
2025-12-28 @ 8:57 AM
Study NCT ID:
NCT05738161
Status:
WITHDRAWN
Last Update Posted:
2024-07-05
First Post:
2023-02-09
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Magrolimab in Combination With Cytotoxic Chemotherapy in Advanced Urothelial Carcinoma
Sponsor:
Insel Gruppe AG, University Hospital Bern
Organization:
Study Overview
Official Title:
A Phase 1, Single Arm Investigator-initiated Study to Investigate the Safety of Combining the Antibody Magrolimab With Standard First Line Platinum-based Chemotherapy (With Cisplatin / Gemcitabine) in Advanced Urothelial Carcinoma
Status:
WITHDRAWN
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
IMP security Issues reported by Sponsor
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MACOCUC-01
Brief Summary:
In their "Magrolimab" research project, the investigators want to find out whether the new drug Magrolimab in combination with conventional chemotherapy is well tolerated and whether survival or progression-free survival improves.
Detailed Description:
About 10% of the patients with urothelial carcinoma of the bladder present with advanced disease at time of diagnosis. The five-year overall survival is poor (13%) as treatment options are limited to platinum-based chemotherapy and immune checkpoint inhibitors. Therefore, new therapeutic approaches are urgently needed.
Stimulation of the innate immune response to cancer cells using macrophages to attack tumor cells represents a novel approach of cancer immunotherapy. One mechanism used by tumor cells to prevent phagocytosis and thus avoid clearance by the immune system is to up regulate "don't eat me" signals such as CD47. Blockade of CD47 represents a novel immunotherapy allowing the immune system to eliminate cancer cells. Cytotoxic chemotherapy, in particular Gemcitabine, is known to upregulate calreticulin which is a so called "eat me" signal. Consequently, a combination of Gemcitabine with an anit-CD47 antibody could potentiate the tumor-cell killing effects.
Magrolimab is a first-in-class fully humanized monoclonal antibody blocking CD47 and currently investigated as an immunotherapy in solid as well as hematologic malignancies in several phase 1 - 3 clinical trials. Furthermore, Magrolimab as a novel myeloid specific immune checkpoint inhibitor could be the urgently needed new therapeutic weapon for bladder cancer treatment if it proves to add a significant therapeutic benefit to conventional chemotherapy in advanced muscle invasive bladder cancer. The expected benefit of combining chemotherapy with Magrolimab might be manifold:
* It could result in durable systemic anti-cancer responses and subsequently increase disease free and overall survival
* It could increase the response rate and prolong survival in the metastatic setting
* In case of positive results of this trial, the investigators could expand this approach to the peri-operative setting:
* In the neoadjuvant setting, it could increase the rate of pathologic complete remission (pCR, ypT0) and subsequently reduce the risk of local recurrence and bladder cancer related death
* In the adjuvant setting, it could induce antitumor immune response in micro metastases and subsequently reduce risk of local recurrence and improve cancer specific survival.
The primary endpoint of the trial is incidence of adverse events (AEs) and laboratory abnormalities according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 Secondary endpoints are
* PFS from date of dose initiation as determined by investigator assessment per RECIST, Version 1.1
* DOR, defined as time from first documentation of complete response or partial response to the earliest date of documented disease progression, per RECIST, Version 1.1, or death from any cause, whichever occurs first, as determined by investigator assessment
* OS, defined as date of dose initiation to death from any cause.
Stimulation of the innate immune response to cancer cells using macrophages to attack tumor cells represents a novel approach of cancer immunotherapy. One mechanism used by tumor cells to prevent phagocytosis and thus avoid clearance by the immune system is to up regulate "don't eat me" signals such as CD47. Blockade of CD47 represents a novel immunotherapy allowing the immune system to eliminate cancer cells. Cytotoxic chemotherapy, in particular Gemcitabine, is known to upregulate calreticulin which is a so called "eat me" signal. Consequently, a combination of Gemcitabine with an anit-CD47 antibody could potentiate the tumor-cell killing effects.
Magrolimab is a first-in-class fully humanized monoclonal antibody blocking CD47 and currently investigated as an immunotherapy in solid as well as hematologic malignancies in several phase 1 - 3 clinical trials. Furthermore, Magrolimab as a novel myeloid specific immune checkpoint inhibitor could be the urgently needed new therapeutic weapon for bladder cancer treatment if it proves to add a significant therapeutic benefit to conventional chemotherapy in advanced muscle invasive bladder cancer. The expected benefit of combining chemotherapy with Magrolimab might be manifold:
* It could result in durable systemic anti-cancer responses and subsequently increase disease free and overall survival
* It could increase the response rate and prolong survival in the metastatic setting
* In case of positive results of this trial, the investigators could expand this approach to the peri-operative setting:
* In the neoadjuvant setting, it could increase the rate of pathologic complete remission (pCR, ypT0) and subsequently reduce the risk of local recurrence and bladder cancer related death
* In the adjuvant setting, it could induce antitumor immune response in micro metastases and subsequently reduce risk of local recurrence and improve cancer specific survival.
The primary endpoint of the trial is incidence of adverse events (AEs) and laboratory abnormalities according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 Secondary endpoints are
* PFS from date of dose initiation as determined by investigator assessment per RECIST, Version 1.1
* DOR, defined as time from first documentation of complete response or partial response to the earliest date of documented disease progression, per RECIST, Version 1.1, or death from any cause, whichever occurs first, as determined by investigator assessment
* OS, defined as date of dose initiation to death from any cause.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 2023-00258 | OTHER | Swiss Association of Research Ethics Committees | View |