Metastatic Urothelial CarcinomaPhase 2CARMANCT06050954
A Pilot Study of Circulating Tumor DNA Adaptive Risk Maintenance Approach for Bladder Cancer (CARMA)
A Phase 2 study testing Pembrolizumab (200mg), Pembrolizumab (400mg) and Monitoring in people with Metastatic Urothelial Carcinoma, run by Fox Chase Cancer Center.
Trial summary
Platinum-based chemotherapy remains the standard of care for advanced/metastatic unresectable bladder cancer. The JAVELIN Bladder 100 and HCRN GU14-182 trials showed that maintenance immune checkpoint inhibition(ICI) for those that achieved disease control could prolong progression-free survival (overall survival… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Urothelial Carcinoma
- What is being tested?
- Pembrolizumab (200mg), Pembrolizumab (400mg) and Monitoring
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Sep 2023to Jan 2032
- Phase
- Phase 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
- Histologically confirmed, unresectable locally advanced or metastatic transitional cell carcinoma of the urothelium.
- Subjects must be deemed eligible for standard first-line platinum-based chemotherapy for advanced or metastatic urothelial cancer (e.g., as per NCCN guidelines). Eligible regimens include; dose-dense MVAC, gemcitabine + cisplatin and/or gemcitabine + carboplatin. (split-dose dosing of cisplatin for dose-dense MVAC and gemcitabine + cisplatin is allowed)
- Must have measureable disease per RECIST v1.1.
- Male or female participants with age ≥ 18 years
- ECOG performance status 0 or 1.
- Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 6 months after the last dose of study treatment
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- Adequate Bone marrow function:
- Absolute neutrophil count (ANC) ≥ 750 /mm3 or ≥0.5 x 109/L
- Platelets ≥50,000/mm3 or ≥100 x 109/L
- Hemoglobin ≥7.5 g/dL (may have been transfused)
- Adequate renal function, defined as estimated creatinine clearance ≥ 45 mL/min (calculated using the Cockcroft-Gault formula or measured with 24-hour urine collection)
- Adequate liver function:
- Total serum bilirubin < 1.5 X ULN (Pts with Gilbert's can enroll if conjugated bilirubin is within normal limits)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 X institutional ULN
- Ability to understand and willingness to sign a written informed consent and HIPAA consent document
Who cannot join
- Prior systemic chemotherapy or radiation therapy for advanced or metastatic urothelial carcinoma.
- Prior immunotherapy with IL-2, IFN-α, or an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA-4 antibody (including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
- Major surgery ≤ 4 weeks or major radiation therapy ≤ 2 weeks prior to enrollment.
- Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided it has not been completed within 48 hours prior to patient enrollment.
- Participants with known symptomatic central nervous system (CNS) metastases requiring steroids. Participants with previously diagnosed CNS metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to randomization, have discontinued corticosteroid treatment for these metastases for at least 4 weeks, and are neurologically stable
- Persisting toxicity related to prior therapy NCI CTCAE v5.0 Grade >1; however, sensory neuropathy Grade ≤ 2 is acceptable.
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- On active treatment for any other malignancy, except for adjuvant hormone therapy for localized breast cancer or castration for hormone sensitive prostate cancer.
- Participation in other studies involving investigational drug(s) within 4 weeks prior to randomization. Observational studies are permitted.
- History of uncontrolled autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Patients with well-controlled autoimmune disease and mild symptoms on a stable dose of prednisone (≤ 10 mg daily) are allowed on study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (defined by current oral or intravenous antibiotic therapy), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients with prior allogeneic hematologic transplant
- Pregnant or breast-feeding.
About this study
Official title: GU-216: A Pilot Study of Circulating Tumor DNA Adaptive Risk Maintenance Approach for Bladder Cancer (CARMA)
Platinum-based chemotherapy remains the standard of care for advanced/metastatic unresectable bladder cancer. The JAVELIN Bladder 100 and HCRN GU14-182 trials showed that maintenance immune checkpoint inhibition(ICI) for those that achieved disease control could prolong progression-free survival (overall survival benefit in JAVELIN may have been related to the lack of guaranteed crossover at time of progression). Of note, both of these studies showed consistency with regards to the magnitude of the PFS benefit which was ~40% vs ~20% at 6-months with maintenance ICI compared to BSC/placebo. Maintenance avelumab is now category 1 on the NCCN guidelines.
However, some patients prefer prolonged chemotherapy responses and literature supports a treatment break without effecting longevity. The underlying risk resides in the selection of patients with some (currently difficult to diagnose) progressing rapidly. This trial proposes to use ctDNA to stratify chemo-responsive patients to active surveillance (i.e. a ctDNA responder referred to here as "ctDNA-") vs SOC maintenance pembrolizumab (ctDNA+). All patients will be treated with SOC chemotherapy and only patients with an objective (RECIST) response will be stratified.
Read more
This is a non-randomized phase 2 study with two arms based on ctDNA
- Pembrolizumab (ctDNA non-responder) maintenance therapy arm (SOC)
- Active surveillance arm (ctDNA responders) with serial ctDNA and crossover 1st line chemotherapy is based on physician discretion choice as described in the protocol. Patients with metastatic Urothelial Cancer are enrolled prior to initiation of SOC chemotherapy. Based on ORR (CR + PR), it is estimated that 75 patients will need to enroll onto the protocol to find 25 responders for the two arms.
- Conditions
- Metastatic Urothelial Carcinoma
- Being tested
- Pembrolizumab (200mg), Pembrolizumab (400mg), Monitoring
- Medical subject headings
- Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pembrolizumab (200mg)Drug
200mg Pembrolizumab every six weeks via IV infusion.
Pembrolizumab (400mg)Drug
400mg Pembrolizumab every six weeks via IV infusion.
MonitoringDiagnostic test
active surveillance and monitoring via continued serial ctDNA testing and radiographic assessments at regular intervals.
| Study group | Role | What they receive |
|---|---|---|
| Maintenance Therapy 200mg Pembrolizumab | Other | Participants who have radiographical or ctDNA progression after 3-6 cycles of standard-of-care platinum-based chemotherapy will be offered 200mg Pembrolizumab every six weeks via IV infusion. Receives: Drug: Pembrolizumab (200mg) |
| Maintenance Therapy 400mg Pembrolizumab | Other | Participants who have radiographical or ctDNA progression after 3-6 cycles of standard-of-care platinum-based chemotherapy will be offered 400mg Pembrolizumab every six weeks via IV infusion.. Receives: Drug: Pembrolizumab (400mg) |
| Active Surveillance | Other | Participants who are deemed ctDNA responders (reduction in ctDNA by 50% or more) on post-chemo testing will undergo active surveillance and continued serial ctDNA testing at regular intervals as defined by the study protocol. Patients will also undergo surveillance imaging as defined in the study protocol. At the time of first radiographic or ctDNA progression (to be assessed every 12 weeks in conjunction with radiographic assessment), the patient will be offered treatment with pembrolizumab. Receives: Diagnostic Test: Monitoring |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients who are progression-free by RECIST 1.1 and alive at six months from initiation of active surveillance.
Measured: 6 months
Secondary outcomes (2)
Overall survival from initial assignment to active surveillance or maintenance arms defined as time to death (or last known alive)
Measured: Up to participant death
Progression-free survival, from initial assignment to maintenance arm defined by RECIST 1.1 or death from any cause.
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 posted22 Sep 2023
- Study startSep 2023 (estimated)
- Primary completionJan 2027 (estimated)
- Study completionJan 2032 (estimated)
Why it stopped: Change in standard of care.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by Fox Chase Cancer CenterThe 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
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fox Chase Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Benjamin Miron, Principal investigator, Fox Chase Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06050954
- Sponsor's protocol ID
- 23-1026
- Acronym
- CARMA
- Status last verified
- Nov 2023
- First submitted
- 11 Sep 2023
- Last updated
- 9 Nov 2023
- Results posted
- No
- 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 9 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GU-216: A Pilot Study of Circulating Tumor DNA Adaptive Risk Maintenance Approach for Bladder Cancer (CARMA)
- ClinicalTrials.gov ID
- NCT06050954
- Acronym / sponsor ID
- CARMA / 23-1026
- Conditions
- Metastatic Urothelial Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Change in standard of care.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Fox Chase Cancer CenterUniversity, hospital or other
- Study start
- Sep 2023 (estimated)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Jan 2032 (estimated)
- First posted
- 22 Sep 2023 (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.
Platinum-based chemotherapy remains the standard of care for advanced/metastatic unresectable bladder cancer. The JAVELIN Bladder 100 and HCRN GU14-182 trials showed that maintenance immune checkpoint inhibition(ICI) for those that achieved disease control could prolong progression-free survival (overall survival benefit in JAVELIN may have been related to the lack of guaranteed crossover at time of progression). Of note, both of these studies showed consistency with regards to the magnitude of the PFS benefit which was ~40% vs ~20% at 6-months with maintenance ICI compared to BSC/placebo. Maintenance avelumab is now category 1 on the NCCN guidelines.
However, some patients prefer prolonged chemotherapy responses and literature supports a treatment break without effecting longevity. The underlying risk resides in the selection of patients with some (currently difficult to diagnose) progressing rapidly. This trial proposes to use ctDNA to stratify chemo-responsive patients to active surveillance (i.e. a ctDNA responder referred to here as "ctDNA-") vs SOC maintenance pembrolizumab (ctDNA+). All patients will be treated with SOC chemotherapy and only patients with an objective (RECIST) response will be stratified.
This is a non-randomized phase 2 study with two arms based on ctDNA
- Pembrolizumab (ctDNA non-responder) maintenance therapy arm (SOC)
- Active surveillance arm (ctDNA responders) with serial ctDNA and crossover 1st line chemotherapy is based on physician discretion choice as described in the protocol. Patients with metastatic Urothelial Cancer are enrolled prior to initiation of SOC chemotherapy. Based on ORR (CR + PR), it is estimated that 75 patients will need to enroll onto the protocol to find 25 responders for the two arms.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Maintenance Therapy 200mg Pembrolizumab | Other | Drug: Pembrolizumab (200mg)Participants who have radiographical or ctDNA progression after 3-6 cycles of standard-of-care platinum-based chemotherapy will be offered 200mg Pembrolizumab every six weeks via IV infusion. |
| Maintenance Therapy 400mg Pembrolizumab | Other | Drug: Pembrolizumab (400mg)Participants who have radiographical or ctDNA progression after 3-6 cycles of standard-of-care platinum-based chemotherapy will be offered 400mg Pembrolizumab every six weeks via IV infusion.. |
| Active Surveillance | Other | Diagnostic Test: MonitoringParticipants who are deemed ctDNA responders (reduction in ctDNA by 50% or more) on post-chemo testing will undergo active surveillance and continued serial ctDNA testing at regular intervals as defined by the study protocol. Patients will also undergo surveillance imaging as defined in the study protocol. At the time of first radiographic or ctDNA progression (to be assessed every 12 weeks in conjunction with radiographic assessment), the patient will be offered treatment with pembrolizumab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histologically confirmed, unresectable locally advanced or metastatic transitional cell carcinoma of the urothelium.
- Subjects must be deemed eligible for standard first-line platinum-based chemotherapy for advanced or metastatic urothelial cancer (e.g., as per NCCN guidelines). Eligible regimens include; dose-dense MVAC, gemcitabine + cisplatin and/or gemcitabine + carboplatin. (split-dose dosing of cisplatin for dose-dense MVAC and gemcitabine + cisplatin is allowed)
- Must have measureable disease per RECIST v1.1.
- Male or female participants with age ≥ 18 years
- ECOG performance status 0 or 1.
Key exclusion criteria (12 listed)
- Prior systemic chemotherapy or radiation therapy for advanced or metastatic urothelial carcinoma.
- Prior immunotherapy with IL-2, IFN-α, or an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA-4 antibody (including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
- Major surgery ≤ 4 weeks or major radiation therapy ≤ 2 weeks prior to enrollment.
- Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided it has not been completed within 48 hours prior to patient enrollment.
- Participants with known symptomatic central nervous system (CNS) metastases requiring steroids. Participants with previously diagnosed CNS metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to randomization, have discontinued corticosteroid treatment for these metastases for at least 4 weeks, and are neurologically stable
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 |
|---|---|---|
| Pembrolizumab (200mg)200mg Pembrolizumab every six weeks via IV infusion. | Drug | Maintenance Therapy 200mg Pembrolizumab |
| Pembrolizumab (400mg)400mg Pembrolizumab every six weeks via IV infusion. | Drug | Maintenance Therapy 400mg Pembrolizumab |
| Monitoringactive surveillance and monitoring via continued serial ctDNA testing and radiographic assessments at regular intervals. | Diagnostic test | Active Surveillance |
Primary outcome
Proportion of patients who are progression-free by RECIST 1.1 and alive at six months from initiation of active surveillance.
Time frame: 6 months
2 secondary outcomes
Overall survival from initial assignment to active surveillance or maintenance arms defined as time to death (or last known alive)
Time frame: Up to participant death
Progression-free survival, from initial assignment to maintenance arm defined by RECIST 1.1 or death from any cause.
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 9 Nov 2023.
- Individual participant dataSharing planned: No
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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.
Benjamin Miron principal investigator
Fox Chase Cancer Center
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab (200mg), Pembrolizumab (400mg) and Monitoring in people with Metastatic Urothelial Carcinoma, run by Fox Chase Cancer Center.
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 15 inclusion and 12 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 9 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
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?
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?
Proportion of patients who are progression-free by RECIST 1.1 and alive at six months from initiation of active surveillance. (time frame: 6 months). 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 9 Nov 2023.