Urinary Bladder NeoplasmsPhase 2NCT04430036
AGEN1884 Plus AGEN2034 Combined With Cisplatin-Gemcitabine for Muscle-Invasive Bladder Cancer
A Phase 2 study testing AGEN1884, AGEN2034 and Cisplatin in people with Urinary Bladder Neoplasms, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
Trial summary
This is a phase II trial to evaluate the tolerability, efficacy, and immune outcomes of AGEN1884 plus AGEN2034 concurrent with cisplatin and gemcitabine in the neoadjuvant treatment of muscle-invasive, non-metastatic bladder cancer prior to radical cystectomy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urinary Bladder Neoplasms
- What is being tested?
- AGEN1884, AGEN2034 and Cisplatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Oct 2020to 14 Mar 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Diagnosis of muscle-invasive, non-metastatic urothelial carcinoma of the bladder, cT2-4, N0-1, M0
- Eligible to receive cisplatin-based chemotherapy, with eligibility defined as meeting all of the following criteria:
- Eastern Cooperative Oncology Group performance status of ¬0-1
- Creatinine clearance (CrCl) of >50 mL/min, as measured by 24-hour urine collection or estimated by the CKD-EPI equation. Patients with CrCl between 50 - 60 mL/min are eligible for the study but will receive split dose cisplatin
- Grade < 2 hearing loss
- Grade < 2 peripheral neuropathy
Show all 19Show fewer
- New York Heart Association Class < III heart failure
- Eligible to receive gemcitabine as dosed here
- Patients must have organ and marrow function meeting the criteria below:
- Absolute neutrophil count > 2,000/mcL Hemoglobin > 9.0 mg/mL Platelets > 100,000/mcL Total bilirubin within normal limits or known to be elevated due to a benign conjugation defect such as Gilbert's syndrome, as evidenced by normal conjugated bilirubin level AST/ALT < 3X institutional normal limits Creatinine clearance (CrCl) > 50 mL/min/1.73m2, as measured with 24 hr urine collection or estimated by CKD-EPI, whichever is greater
- Signed, written informed consents to allow transfer of tumor tissue and production of peptides and to receive experimental treatment and monitoring if agreeable, or monitoring without experimental treatment otherwise
- Age ≥18 years
- Available fresh tissue from surgical excision. If fresh tissue is not available, archival tissue may be used.
- Female subjects of childbearing potential must have a negative serum pregnancy test at screening (within 72 hours of first dose of study medication). Non-childbearing potential (other than by medical reasons) is defined as 1 of the following:
- ≥ 45 years of age and amenorrheic for >1 year by self-report.
- Amenorrheic for >2 years without a hysterectomy and oophorectomy, and follicle-stimulating hormone value in the postmenopausal range upon pretrial (screening) evaluation.
- Status post-hysterectomy, -oophorectomy, or -tubal ligation. If of childbearing potential, female subjects must be willing to use adequate birth control during the study, starting with the screening visit through 120 days after the last dose of study therapy.
- Male subjects with a female partner(s) of childbearing potential must agree to use a condom throughout the trial, starting with the screening visit through 120 days after the last dose of study therapy. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.
- Note: Abstinence is acceptable for both female and male subjects if this is the subject's established and preferred contraception method.
Who cannot join
- Subjects must not have previously received a checkpoint inhibitor ie, anti-PD-1, anti-PD L1, or anti CTLA-4 antibody.
- Subjects must not have previously received anticancer medications or investigational drugs for the disease under study within the following windows:
- ≤ 28 days for prior monoclonal antibody used for anticancer therapy, with the exception of denosumab b. ≤ 7 days for immunosuppressive treatment for any reason, with the following exceptions: i. Physiologic steroid replacement for adrenal insufficiency (e.g., <10 mg prednisone per day) is permitted.
- Use of inhaled or topical corticosteroid for radiographic procedures is permitted.
- Systemic corticosteroids < 7 days are not allowed except as defined above. d. ≤ 28 days before first dose of study drug for all other investigational study drugs or devices
- Has persisting toxicity related to prior therapy of National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE) Grade >1 severity.
Show all 15Show fewer
- Note: Sensory neuropathy or alopecia of Grade ≤2 is acceptable.
- Has known severe hypersensitivity reactions to fully human monoclonal antibodies (NCI-CTCAE Version 5.0 Grade ≥3), any history of anaphylaxis, or uncontrolled asthma.
- Active or history of any autoimmune disease (subjects with diabetes type 1, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible). Patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus or autoimmune vasculitis [e.g., Wegener's Granulomatosis] are excluded from this study.
- Any condition requiring systemic treatment with corticosteroids (>10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroids doses >10mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- Uncontrolled intercurrent illness, including but not limited to uncontrolled infection, interstitial lung disease or active, non-infectious pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or social situations that would limit compliance with study requirements in the opinion of the treating investigator or medical monitor.
- History of intolerance or allergic reactions attributed to compounds of similar chemical or biologic composition to AGEN1884 or AGEN2034.
- Women who are pregnant or breastfeeding.
- Receipt of a live vaccine within 30 days prior to the first dose of study drug.
- Inability to adhere to the protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Trial of Neoadjuvant AGEN1884 Plus AGEN2034 in Combination With Cisplatin-Gemcitabine for Muscle-Invasive Bladder Cancer Prior to Radical Cystectomy
This is a phase II trial to evaluate the tolerability, efficacy, and immune outcomes of AGEN1884 plus AGEN2034 concurrent with cisplatin and gemcitabine in the neoadjuvant treatment of muscle-invasive, non-metastatic bladder cancer prior to radical cystectomy.
Read the detailed description
We will begin with an initial safety run-in to establish the safety of the combination prior to expansion to the full planned phase II. The overall phase II will be an open-label, single arm study in two stages to evaluate the efficacy of the combination in pathologic downstaging of MIBC. Patients will receive four 21-day cycles of neoadjuvant therapy consisting of cisplatin and gemcitabine plus AGEN2034 in all 4 cycles and AGEN1884 in cycles 1 and 3. Patients will proceed to radical cystectomy within 10 weeks after the final dose of this therapy. The primary endpoint of pathologic tumor downstaging will be assessed at the time of cystectomy.
- Conditions
- Urinary Bladder Neoplasms
- Being tested
- AGEN1884, AGEN2034, Cisplatin, Gemcitabine
- Keywords
- muscle-invasive, non-metastatic
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AGEN1884Drug
Also called anti-CTLA-4 antibody
A fully human monoclonal Anti-PD-1 Antibody
AGEN2034Drug
Also called Anti-PD-1
A fully human monoclonal Anti-PD-1 Antibody
CisplatinDrug
Also called Gemzar, Platinol® and Platinol®-AQ
Alkylating antineoplastic agent
GemcitabineDrug
Also called Gebina, Gemalata, Gembin, Gembine, Gembio, Gemcel, Gemcetin
Antimetabolite antineoplastic agent
| Study group | Role | What they receive |
|---|---|---|
| Cisplatin, Gemcitabine plus human monoclonal antibodies | Experimental | The safety run-in of the study will first enroll three patients who will begin treatment with cisplatin and gemcitabine plus AGEN2034 and AGEN1884 as outlined in the treatment plan. These first 3 patients will be assessed for DLTs and there will be a pause in enrollment until all three complete the DLT period. If there are no DLTs in the first 3 patients, we will proceed to further accrual to stage I of phase II. If there is 1 DLT in the initial 3 patients, we will enroll 3 additional patients to the safety run-in. If > 2 DLTs are experienced in the initial 3 patients, the study will be terminated, otherwise additional subjects will be enrolled into the phase ll first stage and reassessed after 2 cycles of therapy and proceed to planned surgery. If criteria are met to continue to the second stage of the Phase II portion of the study, additional patients will be enrolled for an anticipated total of 36 evaluable patients. Patients will be treated and endpoints evaluated. Receives: Drug: AGEN1884; Drug: AGEN2034; Drug: Cisplatin; Drug: Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic Tumor Downstaging of >T2 to pT0
pT0 or pCR (defined as no residual tumor in bladder and lymph nodes on resected specimen). Surgery should be performed within 6 weeks after completing up to 4 cycles (last dose) of neoadjuvant therapy, but can be done up to 10 weeks after treatment ends to be evaluable. Otherwise this patient must be replaced for response evaluation.
Measured: Completion of four 21 day cycles (approximately 10 weeks)
Secondary outcomes (4)
Evaluation of Safety and Tolerability of AGEN1884 Plus AGEN2034 Plus Cisplatin and Gemcitabine
Evaluation of safety and tolerability of using Agen1884 plus AGEN2034 plus cisplating and gemcitabine chemotherapy in the neoadjuvant treatment of muscle-invasive bladder cancer prior to radial cystectomy. Number of adverse events assessed between 3-5 using the National Cancer Institution Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0)
Measured: Baseline to 90 days
Pathologic Downstaging to <T2 Rate
Number of subjects who achieved downstaging of the tumor at completion of the possible 4 chemotherapy cycles.
Measured: Baseline to Completion of four 21 day cycles (approximately 10 weeks)
Completion of Surgery
Number of subjects that progressed from therapy to surgery
Measured: 90 days
Progression-free Survival at 1 Year
Number of subjects that survived to 1 year from study start without disease progression
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2020
- Study start14 Oct 2020
- Primary completion18 Oct 2021
- Study completion14 Mar 2022
Why it stopped: PI left the institution
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Urinary Bladder NeoplasmsStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center at San AntonioThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a phase II trial to evaluate the tolerability, efficacy, and immune outcomes of AGEN1884 plus AGEN2034 concurrent with cisplatin and gemcitabine in the neoadjuvant treatment of muscle-invasive, non-metastatic bladder cancer prior to radical cystectomy. We will begin with an initial safety run-in to establish the safety of the combination prior to expansion to the full planned phase II. The overall phase II will be an open-label, single arm study in two stages to evaluate the efficacy of the combination in pathologic downstaging of MIBC.
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chethan Ramamurthy, MD, Principal investigator, The University of Texas Health Science Center at San Antonio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04430036
- Sponsor's protocol ID
- CTMS 19-0193
- Other IDs
- HSC20200027H
- Status last verified
- Apr 2024
- First submitted
- 8 May 2020
- Last updated
- 4 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Neoadjuvant AGEN1884 Plus AGEN2034 in Combination With Cisplatin-Gemcitabine for Muscle-Invasive Bladder Cancer Prior to Radical Cystectomy
- ClinicalTrials.gov ID
- NCT04430036
- Acronym / sponsor ID
- CTMS 19-0193
- Conditions
- Urinary Bladder Neoplasms
- Keywords
- muscle-invasive, non-metastatic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI left the institution
- Enrolment
- 4 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Study start
- 14 Oct 2020 (actual)
- Primary completion
- 18 Oct 2021 (actual)
- Study completion
- 14 Mar 2022 (actual)
- First posted
- 12 Jun 2020 (actual)
- Results
- Posted 4 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase II trial to evaluate the tolerability, efficacy, and immune outcomes of AGEN1884 plus AGEN2034 concurrent with cisplatin and gemcitabine in the neoadjuvant treatment of muscle-invasive, non-metastatic bladder cancer prior to radical cystectomy.
Detailed description
We will begin with an initial safety run-in to establish the safety of the combination prior to expansion to the full planned phase II. The overall phase II will be an open-label, single arm study in two stages to evaluate the efficacy of the combination in pathologic downstaging of MIBC. Patients will receive four 21-day cycles of neoadjuvant therapy consisting of cisplatin and gemcitabine plus AGEN2034 in all 4 cycles and AGEN1884 in cycles 1 and 3. Patients will proceed to radical cystectomy within 10 weeks after the final dose of this therapy. The primary endpoint of pathologic tumor downstaging will be assessed at the time of cystectomy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a phase II trial to evaluate the tolerability, efficacy, and immune outcomes of AGEN1884 plus AGEN2034 concurrent with cisplatin and gemcitabine in the neoadjuvant treatment of muscle-invasive, non-metastatic bladder cancer prior to radical cystectomy. We will begin with an initial safety run-in to establish the safety of the combination prior to expansion to the full planned phase II. The overall phase II will be an open-label, single arm study in two stages to evaluate the efficacy of the combination in pathologic downstaging of MIBC.
| Arm | Type | Receives |
|---|---|---|
| Cisplatin, Gemcitabine plus human monoclonal antibodies | Experimental | Drug: AGEN1884, Drug: AGEN2034, Drug: Cisplatin, Drug: GemcitabineThe safety run-in of the study will first enroll three patients who will begin treatment with cisplatin and gemcitabine plus AGEN2034 and AGEN1884 as outlined in the treatment plan. These first 3 patients will be assessed for DLTs and there will be a pause in enrollment until all three complete the DLT period. If there are no DLTs in the first 3 patients, we will proceed to further accrual to stage I of phase II. If there is 1 DLT in the initial 3 patients, we will enroll 3 additional patients to the safety run-in. If > 2 DLTs are experienced in the initial 3 patients, the study will be terminated, otherwise additional subjects will be enrolled into the phase ll first stage and reassessed after 2 cycles of therapy and proceed to planned surgery. If criteria are met to continue to the second stage of the Phase II portion of the study, additional patients will be enrolled for an anticipated total of 36 evaluable patients. Patients will be treated and endpoints evaluated. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Diagnosis of muscle-invasive, non-metastatic urothelial carcinoma of the bladder, cT2-4, N0-1, M0
- Eligible to receive cisplatin-based chemotherapy, with eligibility defined as meeting all of the following criteria:
- Eligible to receive gemcitabine as dosed here
- Patients must have organ and marrow function meeting the criteria below:
- Absolute neutrophil count > 2,000/mcL Hemoglobin > 9.0 mg/mL Platelets > 100,000/mcL Total bilirubin within normal limits or known to be elevated due to a benign conjugation defect such as Gilbert's syndrome, as evidenced by normal conjugated bilirubin level AST/ALT < 3X institutional normal limits Creatinine clearance (CrCl) > 50 mL/min/1.73m2, as measured with 24 hr urine collection or estimated by CKD-EPI, whichever is greater
Key exclusion criteria (15 listed)
- Subjects must not have previously received a checkpoint inhibitor ie, anti-PD-1, anti-PD L1, or anti CTLA-4 antibody.
- Subjects must not have previously received anticancer medications or investigational drugs for the disease under study within the following windows:
- Has persisting toxicity related to prior therapy of National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE) Grade >1 severity.
- Note: Sensory neuropathy or alopecia of Grade ≤2 is acceptable.
- Has known severe hypersensitivity reactions to fully human monoclonal antibodies (NCI-CTCAE Version 5.0 Grade ≥3), any history of anaphylaxis, or uncontrolled asthma.
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 |
|---|---|---|
| AGEN1884Also: anti-CTLA-4 antibodyA fully human monoclonal Anti-PD-1 Antibody | Drug | Cisplatin, Gemcitabine plus human monoclonal antibodies |
| AGEN2034Also: Anti-PD-1A fully human monoclonal Anti-PD-1 Antibody | Drug | Cisplatin, Gemcitabine plus human monoclonal antibodies |
| CisplatinAlso: Gemzar, Platinol® and Platinol®-AQAlkylating antineoplastic agent | Drug | Cisplatin, Gemcitabine plus human monoclonal antibodies |
| GemcitabineAlso: Gebina, Gemalata, Gembin, Gembine, Gembio, Gemcel, GemcetinAntimetabolite antineoplastic agent | Drug | Cisplatin, Gemcitabine plus human monoclonal antibodies |
Primary outcome
Pathologic Tumor Downstaging of >T2 to pT0
Time frame: Completion of four 21 day cycles (approximately 10 weeks)
pT0 or pCR (defined as no residual tumor in bladder and lymph nodes on resected specimen). Surgery should be performed within 6 weeks after completing up to 4 cycles (last dose) of neoadjuvant therapy, but can be done up to 10 weeks after treatment ends to be evaluable. Otherwise this patient must be replaced for response evaluation.
4 secondary outcomes
Evaluation of Safety and Tolerability of AGEN1884 Plus AGEN2034 Plus Cisplatin and Gemcitabine
Time frame: Baseline to 90 days
Pathologic Downstaging to <T2 Rate
Time frame: Baseline to Completion of four 21 day cycles (approximately 10 weeks)
Completion of Surgery
Time frame: 90 days
Progression-free Survival at 1 Year
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Urinary Bladder Neoplasms
RecruitingPhase 3
A Clinical Trial of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) and Pembrolizumab (MK-3475A) in Participants With Bladder Cancer (MK-2870-055)
Bladder Cancer
Active, not recruitingPhase 2/3
A Study of CTX-009 in Combination With Paclitaxel in Adult Patients With Unresectable Advanced, Metastatic or Recurrent Biliary Tract Cancers (COMPANION-002)
Biliary Tract Cancer, Cholangiocarcinoma
Recruiting
Effect of Cyclic Sighing Breathing Exercise on CRBD, Pain, and Sleep Quality in Patients Undergoing TUR
Transurethral Resection of Bladder Tumor, Transurethral Resection of the Prostate (TURP)
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
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.
Chethan Ramamurthy, MD principal investigator
The University of Texas Health Science Center at San Antonio
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AGEN1884, AGEN2034 and Cisplatin in people with Urinary Bladder Neoplasms, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
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 19 inclusion and 15 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: stopped early, as of the sponsor's last update on 4 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 phase mean?
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?
Yes. Results are posted in the registry (first posted 4 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Pathologic Tumor Downstaging of >T2 to pT0 (time frame: Completion of four 21 day cycles (approximately 10 weeks)). 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 4 Apr 2024.