Bladder CancerPhase 2NCT03980041
Study to Evaluate the Efficacy/Safety of IPI-549 in Combination With Nivolumab in Patients With Advanced Urothelial Carcinoma (MARIO-275)
A Phase 2 study testing IPI-549 (eganelisib) and Nivolumab in people with Bladder Cancer and Urothelial Carcinoma, run by Infinity Pharmaceuticals, Inc. at 29 sites in 7 countries.
Trial summary
The purpose of this study is to measure the effect of IPI-549 in combination with nivolumab when compared to nivolumab monotherapy in advanced urothelial cancer patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Cancer, Urothelial Carcinoma, Solid Tumor
- What is being tested?
- IPI-549 (eganelisib) and Nivolumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 49 participants
- Where
- 29 sitesin 7 countries
- Study dates
- 25 Sep 2019to 15 Nov 2022
- 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 or cytologically confirmed urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra
- Measurable disease by CT or MRI as defined by RECIST v1.1
- Disease progression or recurrence after treatment:
- i) With at least 1 platinum-based chemotherapy regimen for the treatment of metastatic (Stage IV) or locally advanced unresectable disease; or
- ii) With disease recurrence within 1 year of completing a platinum-based neoadjuvant or adjuvant therapy
- Subject that have received more than 2 prior lines of chemotherapy must not have liver metastases
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- Tumor tissues (archived or new biopsy) must be provided for biomarker analysis
- Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- Blood sample must be provided for mMDSC levels for randomization into the study
Who cannot join
- Active brain metastases or leptomeningeal metastases
- Any serious or uncontrolled medical disorder that may interfere with study treatment/interpretation
- Prior malignancy active within the previous 3 years except for local or organ confined early stage cancer that has been apparently cured
- Active, known, or suspected autoimmune disease
- A condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 day of study drug administration
- Prior therapy with anti-tumor vaccines, any T cell co-stimulation or checkpoint pathways, or IPI-549
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- Prior surgery or gastrointestinal dysfunction that may affect drug absorption
- Past medical history of interstitial lung disease
- History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control
- Positive test for hepatitis B, C or HIV
- Dependent on continuous supplemental oxygen
Trial locations and contacts
29 sites in 7 countries.
29 sites in 7 countries
Spain8 sites
ICO Institute Catalan of Oncology
Barcelona, 08907
Hospital de Sant Creu i Sant Pau
Barcelona, 8005
IMQ Zorrotzaurre
Bilbao, 48180
MD Anderson Cancer Center Madrid
Madrid, 28033
Hospital Ramón y Cajal
Madrid, 28034
Hospital Universitatio HM Sanchinarro
Madrid, 28050
Hospital Universitario Central de Asturias
Oviedo, 33011
Hospital Universitario
Seville, 41013
United States7 sites
University of MD - Greenebaum Comprehensive Cancer Center
Baltimore, Maryland, 21201
Karmanos Cancer Center
Detroit, Michigan, 48201
Parkview Physicians
Fort Wayne, Indiana, 46845
Bon Secours St. Francis Cancer Center
Greenville, South Carolina, 29607
Sarah Cannon Tennessee Oncology
Nashville, Tennessee, 37203
Coborn Cancer Center
Saint Cloud, Minnesota, 56303
Montefiore Medical Center
The Bronx, New York, 10461
France5 sites
Centre Oscar Lambret
Lille, 59020
Institut Paoli-Calmettes
Marseille, 13009
Centre Antoine Lacassagne
Nice, 06189
CHU de Strasbourg
Strasbourg, 67000
Institut Claudius Regaud
Toulouse, 31300
Italy3 sites
Istituto per la Ricerca e la Cura del Cancro (IRCC)
Candiolo, 10060
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola, 47104
Istituto Nazionale dei Tumori
Naples, 80131
Poland3 sites
Oddzial Chorob Rozrostowych Wojewodzki Szpital
Lodz, 93-153
Dzienny Oddzial Chemioterapii
Racibórz, 47-400
EXAMEN sp
Skorzewo, 60-185
Serbia2 sites
Clinical Centre of Serbia
Belgrade, 11 000
Institute for Oncology of Vojvodina
Kamenitz, 21 204
About this study
Official title: A Phase 2, Multicenter, Randomized, Double-Blind, Active-Control Study to Evaluate the Efficacy and Safety of Nivolumab Administered in Combination With IPI-549 Compared to Nivolumab Monotherapy in the Treatment of Patients With Immune Therapy-Naïve, Advanced Urothelial Carcinoma
The purpose of this study is to measure the effect of IPI-549 in combination with nivolumab when compared to nivolumab monotherapy in advanced urothelial cancer patients.
Read the detailed description
Study IPI-549-02 is a multi-national, prospective, randomized, active-control Phase II trial to evaluate the efficacy and safety of IPI 549 administered in combination with nivolumab compared to nivolumab monotherapy.
The study will enroll approximately 160 checkpoint-naïve, advanced urothelial cancer patients who have progressed or recurred following treatment with platinum-based chemotherapy. Patients will be randomized 2:1 to receive intravenous (IV) nivolumab 480 mg every 4 weeks (Q4W) in combination with oral (PO) IPI 549 40 mg once daily (QD) or IV nivolumab 480 mg Q4W in combination with placebo PO QD.
Eligible patients who have confirmed progression of disease during treatment with nivolumab monotherapy may crossover to the combination treatment arm.
- Conditions
- Bladder Cancer, Urothelial Carcinoma, Solid Tumor, Advanced Cancer
- Being tested
- IPI-549 (eganelisib), Nivolumab, Placebos
- Keywords
- eganelisib, IPI-549
- Medical subject headings
- Urinary Bladder Neoplasms, Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IPI-549 (eganelisib)Drug
Also called IPI549
IPI-549 (40mg QD) administered orally in 28-day cycles
NivolumabDrug
Also called OPDIVO®
Nivolumab (480mg Q4W) administered intravenously (IV) in 28-day cycles
PlacebosDrug
Also called Placebo
Placebo administered orally in 28-day cycles
| Study group | Role | What they receive |
|---|---|---|
| IPI-549 + Nivolumab | Experimental | Participants receive IPI-549 orally (PO) daily in combination with nivolumab IV infusion every 4 weeks Receives: Drug: IPI-549 (eganelisib); Drug: Nivolumab |
| Placebo + Nivolumab | Active comparator | Participants receive placebo orally (PO) daily in combination with nivolumab IV infusion every 4 weeks Receives: Drug: Nivolumab; Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR) per RECISTv1.1
ORR is defined as best response of complete response (CR) or partial response (PR) as measured by RECIST v1.1.
RECIST 1.1 = Response Evaluation Criteria in Solid Tumors. CR= Disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis. PR= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Measured: First dosing date to date of confirmed disease progression, assessed up to 24 months
Secondary outcomes (12)
Time to Response (TTR)
TTR is defined as the time from the first dose of study treatment to first objective response [complete response (CR) or partial response (PR)] in patients with CR or PR.
Measured: First dosing date to date of first objective response, assessed up to 24 months
Duration of Response (DOR)
DOR is defined as the time from the first objective response (CR or PR) to documented disease progression in patients with CR or PR.
Measured: Date of first objective response to date of confirmed disease progression, assessed up to 24 months
Progression-Free Survival (PFS)
PFS is defined as the time from the first dose of study treatment to documented disease progression or death due to any cause.
Measured: First dosing to date to confirmed disease progression or death, assessed up to 48 months
Changes from baseline in thyroid stimulating hormone (TSH)
If TSH result is abnormal, subsequent testing of Free T3 and free T4 required.
Measured: Pre-treatment (within 7 days of first dose) to date of confirmed disease progression, assessed up to 24 months
Changes from baseline in electrocardiograms (ECGs)
ECGs assess heart problems by measuring the electrical activity generated by the heart as it contracts. The components that will be assessed during the ECG are P wave, QRS complex, ST segment, and T wave.
Measured: Screening to date of confirmed disease progression, assessed up to 24 months
Changes from baseline in Eastern Cooperative Oncology Group (ECOG) performance
ECOG performance status describes the level of impact that disease has on the patient's daily living abilities. Scale ranges from 0 (Fully active and able to carry on all pre-disease performance without restriction) to 5 (Dead).
Measured: Screening to date of confirmed disease progression, assessed up to 24 months
Population Pharmacokinetics (PK) of IPI-549-01
IPI-549 blood concentrations in ng/mL.
Measured: Pre-dose, 0.5, 1.5, 3 and 6 hours following administration on Day 1 of Cycles 1 and 2 (each cycle is 28 days)
Pharmacokinetics (PK) of Nivolumab
Nivolumab blood concentrations will be assayed in ug/mL.
Measured: Pre-infusion and within 2 minutes of end of infusion on Day 1 of Cycles 1 and 4; Pre-infusion on Day 1 of Cycles 2 and 3, and every 4 cycles starting at Cycle 5 (each cycle is 28 days)
Changes from baseline in pulse rate
Pulse rate as measured in beats per minute (bpm)
Measured: Screening to date of confirmed disease progression, assessed up to 24 months
Changes from baseline in temperature
Temperature as measured in celsius.
Measured: Screening to date of confirmed disease progression, assessed up to 24 months
Changes from baseline in respiration rate
Respiration rate as measured in breaths per minute.
Measured: Screening to date of confirmed disease progression, assessed up to 24 months
Changes from baseline in blood pressure
Systolic and diastolic blood pressure as measured in mmHg.
Measured: Screening to date of confirmed disease progression, assessed up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2019
- Study start25 Sep 2019
- Primary completion30 Nov 2020
- Study completion15 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bladder CancerStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Infinity Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Halle Zhang, PhD, RN, Study director, Infinity Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03980041
- Sponsor's protocol ID
- IPI-549-02
- Status last verified
- Nov 2022
- First submitted
- 22 Apr 2019
- Last updated
- 25 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- 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 25 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Multicenter, Randomized, Double-Blind, Active-Control Study to Evaluate the Efficacy and Safety of Nivolumab Administered in Combination With IPI-549 Compared to Nivolumab Monotherapy in the Treatment of Patients With Immune Therapy-Naïve, Advanced Urothelial Carcinoma
- ClinicalTrials.gov ID
- NCT03980041
- Acronym / sponsor ID
- IPI-549-02
- Conditions
- Bladder Cancer, Urothelial Carcinoma, Solid Tumor, Advanced Cancer
- Keywords
- eganelisib, IPI-549
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Infinity Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Study start
- 25 Sep 2019 (actual)
- Primary completion
- 30 Nov 2020 (actual)
- Study completion
- 15 Nov 2022 (actual)
- First posted
- 10 Jun 2019 (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.
The purpose of this study is to measure the effect of IPI-549 in combination with nivolumab when compared to nivolumab monotherapy in advanced urothelial cancer patients.
Detailed description
Study IPI-549-02 is a multi-national, prospective, randomized, active-control Phase II trial to evaluate the efficacy and safety of IPI 549 administered in combination with nivolumab compared to nivolumab monotherapy.
The study will enroll approximately 160 checkpoint-naïve, advanced urothelial cancer patients who have progressed or recurred following treatment with platinum-based chemotherapy. Patients will be randomized 2:1 to receive intravenous (IV) nivolumab 480 mg every 4 weeks (Q4W) in combination with oral (PO) IPI 549 40 mg once daily (QD) or IV nivolumab 480 mg Q4W in combination with placebo PO QD.
Eligible patients who have confirmed progression of disease during treatment with nivolumab monotherapy may crossover to the combination treatment arm.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IPI-549 + Nivolumab | Experimental | Drug: IPI-549 (eganelisib), Drug: NivolumabParticipants receive IPI-549 orally (PO) daily in combination with nivolumab IV infusion every 4 weeks |
| Placebo + Nivolumab | Active comparator | Drug: Nivolumab, Drug: PlacebosParticipants receive placebo orally (PO) daily in combination with nivolumab IV infusion every 4 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histologically or cytologically confirmed urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra
- Measurable disease by CT or MRI as defined by RECIST v1.1
- Disease progression or recurrence after treatment:
- i) With at least 1 platinum-based chemotherapy regimen for the treatment of metastatic (Stage IV) or locally advanced unresectable disease; or
- ii) With disease recurrence within 1 year of completing a platinum-based neoadjuvant or adjuvant therapy
Key exclusion criteria (11 listed)
- Active brain metastases or leptomeningeal metastases
- Any serious or uncontrolled medical disorder that may interfere with study treatment/interpretation
- Prior malignancy active within the previous 3 years except for local or organ confined early stage cancer that has been apparently cured
- Active, known, or suspected autoimmune disease
- A condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 day of study drug administration
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 |
|---|---|---|
| IPI-549 (eganelisib)Also: IPI549IPI-549 (40mg QD) administered orally in 28-day cycles | Drug | IPI-549 + Nivolumab |
| NivolumabAlso: OPDIVO®Nivolumab (480mg Q4W) administered intravenously (IV) in 28-day cycles | Drug | IPI-549 + Nivolumab, Placebo + Nivolumab |
| PlacebosAlso: PlaceboPlacebo administered orally in 28-day cycles | Drug | Placebo + Nivolumab |
Primary outcome
Objective Response Rate (ORR) per RECISTv1.1
Time frame: First dosing date to date of confirmed disease progression, assessed up to 24 months
ORR is defined as best response of complete response (CR) or partial response (PR) as measured by RECIST v1.1. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors. CR= Disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis. PR= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
12 secondary outcomes
Time to Response (TTR)
Time frame: First dosing date to date of first objective response, assessed up to 24 months
Duration of Response (DOR)
Time frame: Date of first objective response to date of confirmed disease progression, assessed up to 24 months
Progression-Free Survival (PFS)
Time frame: First dosing to date to confirmed disease progression or death, assessed up to 48 months
Changes from baseline in thyroid stimulating hormone (TSH)
Time frame: Pre-treatment (within 7 days of first dose) to date of confirmed disease progression, assessed up to 24 months
Changes from baseline in electrocardiograms (ECGs)
Time frame: Screening to date of confirmed disease progression, assessed up to 24 months
Changes from baseline in Eastern Cooperative Oncology Group (ECOG) performance
Time frame: Screening to date of confirmed disease progression, assessed up to 24 months
Population Pharmacokinetics (PK) of IPI-549-01
Time frame: Pre-dose, 0.5, 1.5, 3 and 6 hours following administration on Day 1 of Cycles 1 and 2 (each cycle is 28 days)
Pharmacokinetics (PK) of Nivolumab
Time frame: Pre-infusion and within 2 minutes of end of infusion on Day 1 of Cycles 1 and 4; Pre-infusion on Day 1 of Cycles 2 and 3, and every 4 cycles starting at Cycle 5 (each cycle is 28 days)
Changes from baseline in pulse rate
Time frame: Screening to date of confirmed disease progression, assessed up to 24 months
Changes from baseline in temperature
Time frame: Screening to date of confirmed disease progression, assessed up to 24 months
Changes from baseline in respiration rate
Time frame: Screening to date of confirmed disease progression, assessed up to 24 months
Changes from baseline in blood pressure
Time frame: Screening to date of confirmed disease progression, assessed up to 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2022.
- Related InfoLink provided by the sponsor.
- 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.
Halle Zhang, PhD, RN study director
Infinity Pharmaceuticals, Inc.
29 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IPI-549 (eganelisib) and Nivolumab in people with Bladder Cancer and Urothelial Carcinoma, run by Infinity Pharmaceuticals, Inc. at 29 sites in 7 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 9 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: finished, as of the sponsor's last update on 25 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in Spain, United States, France, Italy, Poland and 2 more countries. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Objective Response Rate (ORR) per RECISTv1.1 (time frame: First dosing date to date of confirmed disease progression, assessed up to 24 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 25 Nov 2022.