- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04430036
AGEN1884 Plus AGEN2034 Combined With Cisplatin-Gemcitabine for Muscle-Invasive Bladder Cancer
A Phase II Trial of Neoadjuvant AGEN1884 Plus AGEN2034 in Combination With Cisplatin-Gemcitabine for Muscle-Invasive Bladder Cancer Prior to Radical Cystectomy
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Texas
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San Antonio, Texas, United States, 78229
- Mays Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria
- 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
- 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.
Exclusion Criteria
- 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:
a. ≤ 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.
ii. Use of inhaled or topical corticosteroid for radiographic procedures is permitted.
c. 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.
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Cisplatin, Gemcitabine plus human monoclonal antibodies
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.
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A fully human monoclonal Anti-PD-1 Antibody
Other Names:
A fully human monoclonal Anti-PD-1 Antibody
Other Names:
Alkylating antineoplastic agent
Other Names:
Antimetabolite antineoplastic agent
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pathologic Tumor Downstaging of >T2 to pT0
Time Frame: Completion of four 21 day cycles (approximately 10 weeks)
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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.
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Completion of four 21 day cycles (approximately 10 weeks)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Evaluation of Safety and Tolerability of AGEN1884 Plus AGEN2034 Plus Cisplatin and Gemcitabine
Time Frame: Baseline to 90 days
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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)
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Baseline to 90 days
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Pathologic Downstaging to <T2 Rate
Time Frame: Baseline to Completion of four 21 day cycles (approximately 10 weeks)
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Number of subjects who achieved downstaging of the tumor at completion of the possible 4 chemotherapy cycles.
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Baseline to Completion of four 21 day cycles (approximately 10 weeks)
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Completion of Surgery
Time Frame: 90 days
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Number of subjects that progressed from therapy to surgery
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90 days
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Progression-free Survival at 1 Year
Time Frame: 1 year
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Number of subjects that survived to 1 year from study start without disease progression
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1 year
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Correlate Immune Outcomes
Time Frame: 2 years
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To correlate clinical outcomes with immune and biologic endpoints and identify patient and tumor characteristics that can predict treatment responses
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2 years
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Collaborators and Investigators
Investigators
- Principal Investigator: Chethan Ramamurthy, MD, University of Texas Health Science Center San Antonio
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Urologic Diseases
- Urinary Bladder Diseases
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Urinary Bladder Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Cisplatin
- Gemcitabine
Other Study ID Numbers
- CTMS 19-0193
- HSC20200027H (Other Identifier: UT Health Science Center San Antonio IRB)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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