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Urothelial CarcinomaPhase 1/2ICRANCT03871036

Improve Checkpoint-blockade Response in Advanced Urothelial Cancer

A Phase 1/2 study testing Tremelimumab, Durvalumab and Paclitaxel in people with Urothelial Carcinoma, run by The Netherlands Cancer Institute at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This trial will include metastatic urothelial carcinoma patients who progressed during or after treatment with anti-PD(L)1 therapy and have been treated by a platinum-containing regimen, or are cisplatin-ineligible. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Urothelial Carcinoma
What is being tested?
Tremelimumab, Durvalumab and Paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
1 siteNetherlands
Study dates
1 May 2019to 15 Jan 2025
Phase
Phase 1/2
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

  • For inclusion in the study, patients should fulfill the following criteria:
  • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (eg, European Union [EU] Data Privacy Directive) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
  • Patients with histologically or cytologically documented metastatic or irresectable (i.e. T4b, N1-3 and/or M1a/b) urothelial cell carcinoma (including renal pelvis, ureters, urinary bladder, and urethra).
  • Patients ineligible for cisplatin-based chemotherapy OR previous treatment with platinum-based chemotherapy, either in the neo-adjuvant setting or in any other setting. This is defined as progression on or after at least 2 cycles of platinum-based chemotherapy (e.g. MVAC, cisplatin/gemcitabine, carpoblatin/gemcitabine). Patients who had to stop platinum-based therapy because of toxicity after at least 2 cycles are eligible if progressive disease has been confirmed.
  • Previous treatment with anti-PD(L)1 immunotherapy. The following conditions apply for inclusion:
  • Must not have experienced a toxicity that led to permanent discontinuation of prior anti-PD(L)1 immunotherapy;
Show all 30Show fewer
  • All treatment-related AEs while receiving prior anti-PD(L)1 immunotherapy must have completely resolved or resolved to baseline prior to screening for this study;
  • Must not have experienced a ≥Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior anti-PD(L)1 immunotherapy;
  • Patients with endocrine AE of ≤Grade 2 are permitted to enroll if the AEs are stably maintained on appropriate replacement therapy and are asymptomatic;
  • Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of >10 mg prednisone or equivalent per day;
  • At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes which must have a Revised Clinical Study Protocol short axis ≥15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and that is suitable for accurate repeated measurements as per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) guidelines.
  • Age >18 years at time of study entry.
  • World Health Organisation (WHO) performance status of 0 or 1.
  • Body weight >30kg.
  • Adequate normal organ and marrow function as defined below:
  • Haemoglobin ≥9.0 g/dL = 5.6 mmol/L;
  • Absolute neutrophil count (ANC) ≥1.5 x 109/L;
  • Platelet count ≥100 x 109/L;
  • Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). (Does not apply to patients with confirmed Gilbert's syndrome, who will be allowed only in consultation with the treating physician);
  • AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN;
  • Measured creatinine clearance (CL) >30 mL/min or Calculated creatinine clearance CL>30 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
  • Males:
  • Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)
  • Females:
  • Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)
  • Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal in case of amenorrhoeu for 12 months without an alternative medical cause. The following age-specific requirements apply:
  • Women <50 years of age would be considered post-menopausal in case of amenorrhea for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy);
  • Women ≥50 years of age would be considered post-menopausal in case of amenorrhea for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy);
  • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • Must have a life expectancy of at least 12 weeks

Who cannot join

  • Patients should not enter the study if any of the following exclusion criteria are fulfilled:
  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
  • Participation in another clinical study with an investigational product during the last 4 weeks.
  • Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
  • Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolization, monoclonal antibodies) ≤28 days prior to the first dose of study drug.
  • Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
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  • Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician;
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician;
  • Toxicity caused by treatment with anti-PD(L)1 should return to baseline, except for endocrine toxicity on a stable dose of replacement therapy.
  • Any concurrent chemotherapy, investigational product (IP), biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
  • Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug.
  • Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
  • History of allogenic organ transplantation.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
  • Patients with vitiligo or alopecia;
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement;
  • Any chronic skin condition that does not require systemic therapy. Psoriasis, if not treated by immunesuppressants, is allowed;
  • Patients without active disease in the last 5 years may be included but only after consultation with the study physician;
  • Patients with celiac disease controlled by diet alone.
  • Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
  • History of another primary malignancy except for:
  • Malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of IP and of low potential risk for recurrence;
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease;
  • Adequately treated carcinoma in situ without evidence of disease;
  • Curatively treated localized prostate cancer without PSA recurrence.
  • History of leptomeningeal carcinomatosis.
  • Brain metastases or spinal cord compression, unless radiographically stable, defined as 2 brain images, both of which are obtained after treatment to the brain metastases. These imaging scans should both be obtained at least four weeks apart and show no evidence of intracranial progression. In addition, any neurologic symptoms that developed either as a result of the brain metastases or treatment thereof must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of ≤10mg/day of prednisone or its equivalent for at least 14 days prior to the start of treatment.. Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry.
  • History of active primary immunodeficiency.
  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection);
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent;
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
  • Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of tremelimumab, durvalumab, or durvalumab + tremelimumab combination therapy.
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
  • Prior randomisation or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment.
  • Previous treatment with anti-CTLA-4 immunotherapy.
  • Known allergy or hypersensitivity to IP or any excipient. Procedures for withdrawal of incorrectly enrolled patients are presented in Section 4.3 of the clinical protocol. If a patient withdraws from participation in the study, then that specific enrollment/randomization code cannot be reused. Withdrawn patients will not be replaced.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Antoni van Leeuwenhoek Ziekenhuis

    Amsterdam

Other trials in Netherlands

About this study

Official title: ICRA (Improve Checkpoint-blockade Response in Advanced Urothelial Cancer), an Adaptive Clinical Study to Determine Efficacy of Combining Weekly Paclitaxel With Tremelimumab +/- Durvalumab (MEDI4736)

This trial will include metastatic urothelial carcinoma patients who progressed during or after treatment with anti-PD(L)1 therapy and have been treated by a platinum-containing regimen, or are cisplatin-ineligible. Patients will receive either paclitaxel in combination with durvalumab (anti-PDL-1) and a single dose (300 mg) of tremelimumab (anti-CTLA4), or paclitaxel with only a high dose of tremelimumab (750 mg). Tremelimumab (750 mg), without paclitaxel will be used as a comparison arm.

A run-in safety phase will be followed by a non-comparative 3-arm randomized study with a Simon's 2-stage optimal design.

Read the detailed description

This trial will include metastatic urothelial carcinoma patients who progressed during or after treatment with anti-PD(L)1 therapy and have been treated by a platinum-containing regimen, or are cisplatin-ineligible.

A run-in safety phase will be followed by a non-comparative 3-arm randomized study with a Simon's 2-stage optimal design.

Screening:

Before enrollment, patients will need to complete the following screening procedures (among other assessments):

  • Baseline evaluation by CT chest/abdomen/pelvis (<4 weeks)
  • Laboratory assessment
  • Tissue biopsy (in at least 6 patients per arm)

Run-in phase-1 (R1): n=3 patients will be treated with:

  • paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6
  • tremelimumab 75 mg on day 1 of cycles 2-6 and then every 12 weeks until week 45

Run-in phase-2 (R2): n=3 patients will be treated with:

  • paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6
  • tremelimumab 225 mg on day 1 of cycles 2-6 and then every 12 weeks until week 45

Run-in phase-3 (R3): n=2 x 3 patients will be randomized over 2 arms:

  • paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6
  • tremelimumab 750 mg on day 1 of cycles 2-6 and then every 12 weeks until week 45 OR
  • paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6
  • tremelimumab 75 mg on day 1 of cycles 2-5
  • durvalumab 1500 mg on day 1 of cycles 2-12, every four weeks (until week 49)

Run-in phase-4 (R4): n=3 patients will be treated with:

  • paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6
  • tremelimumab 300 mg once on day 1 of cycle 2
  • durvalumab 1500 mg on day 1 of cycles 2-12, every four weeks (until week 49)

Enrollment will start with the first run-in cohort (R1) and will be halted after inclusion of the 3rd patient, until 60 days after start of treatment of this patient. Stopping rules are defined in the section 6.3 of the protocol. In case unexpected toxicity occurs (either as defined by the stopping rules or otherwise unexpected severe toxicity), the study team will discuss with the IDMC whether expansion to include 3 additional subjects is warranted. If no unexpected toxicity has occurred within 60 days after initiation of treatment of the 3rd patient of R1, enrollment for R2 will begin in a similar fashion. If 2 or more nonhematological toxicities as described in section 6.3 "Definition of DLT" occur in R1 or R2, enrollment will be suspended until the IDMC has formulated an advice. After this advice, the sponsor will decide on continuation.

If no unexpected toxicity has occurred within 60 days after initiation of treatment of the 3rd patient of R2, the study will continue with a third run-in cohort (R3) where patients will be randomized over 2 arms (R3A and R3B), n=3 per arm. If no unexpected toxicity has occurred within 60 days after initiation of treatment of the 3rd patient in arm R3A, this arm will be continued into the main study phase (as Arm A). If unacceptable toxicity is observed at either 225 mg or 750 mg of tremelimumab during one of the run-in cohorts, a lower dose level can be used in the main study. In addition, after completion of R3A and continuation in the main study phase, a control arm (Arm C) will be initiated where patients will be treated with tremelimumab monotherapy (without paclitaxel).

If no unexpected toxicity has occurred within 60 days after initiation of treatment of the 3rd patient of R3B, enrollment for run-in cohort R4 will begin in a similar fashion as described for the earlier run-in cohorts. Expansion arms A and C will be paused while this cohort is enrolling. If no unexpected toxicity has occurred within 60 days after initiation of treatment of the 3rd patient of R4, enrollment for arm R4 will be continued into the main study phase (as Arm B). If unacceptable toxicity is observed at 300 mg of tremelimumab in combination with 1500mg durvalumab, arm B, combining paclitaxel, tremelimumab and durvalumab, will be discontinued.

Main study:

Arm A:

  • paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6
  • tremelimumab 750 mg on day 1 of cycles 2-6 and then every 12 weeks until week 45

Arm B:

  • paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6
  • tremelimumab 300 mg once on day 1 of cycle 2
  • durvalumab 1500 mg on day 1 of cycles 2-12, every four weeks (until week 49)

Arm C (control arm):

  • tremelimumab 750 mg on day 1 of cycles 1-5 and then every 12 weeks until week 41

Enrollment will be halted when 12 patients are enrolled in each arm; this will include patients treated in R3 and R4 at the dose level used in the main study. These patients will be included in the efficacy analysis.

After the last patient has had the second evaluation scan, the Objective Response Rate (ORR) of each treatment arm will be evaluated. If one or more of the experimental arms has ≥2 responses, the study team will discuss continuation of one of the experimental arms to n=20 with the IDMC. In case 2 responses are seen in one of the arms prior to the second evaluation scan of the last patient, a decision on expansion of that arm may be recommended earlier.

Keywords
Advanced urothelial carcinoma, Checkpoint inhibition, Tremelimumab, Durvalumab, Paclitaxel
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.

  • TremelimumabDrug

    Also called Ticilimumab, CP-675,206

    See experimental arm description for more details.

  • DurvalumabDrug

    Also called Imfinzi, MEDI4736

    See experimental arm description for more details.

  • PaclitaxelDrug

    Also called Taxol

    See experimental arm description for more details.

Study groups in NCT03871036
Study groupRoleWhat they receive
Tremelimumab 75 (R1)ExperimentalRun-in phase-1 (R1): n=3 patients will be treated with: * paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6 * tremelimumab 75 mg on day 1 of cycles 2-6 and then every 12 weeks until week 45
Receives: Drug: Tremelimumab; Drug: Paclitaxel
Tremelimumab 225 (R2)ExperimentalRun-in phase-2 (R2): n=3 patients will be treated with: * paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6 * tremelimumab 225 mg on day 1 of cycles 2-6 and then every 12 weeks until week 45
Receives: Drug: Tremelimumab; Drug: Paclitaxel
Tremelimumab vs Tremelimumab+Durvalumab (R3)ExperimentalRun-in phase-3 (R3): n=2 x 3 patients will be randomized over 2 arms: * paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6 * tremelimumab 750 mg on day 1 of cycles 2-6 and then every 12 weeks until week 45 OR * paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6 * tremelimumab 75 mg on day 1 of cycles 2-5 * durvalumab 1500 mg on day 1 of cycles 2-12, every four weeks (until week 49)
Receives: Drug: Tremelimumab; Drug: Durvalumab; Drug: Paclitaxel
Tremelimumab 300 (R4)ExperimentalRun-in phase-4 (R4): n=3 patients will be treated with: * paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6 * tremelimumab 300 mg once on day 1 of cycle 2 * durvalumab 1500 mg on day 1 of cycles 2-12, every four weeks (until week 49)
Receives: Drug: Tremelimumab; Drug: Durvalumab; Drug: Paclitaxel
Tremelimumab 750 (A)ExperimentalArm A: * paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6 * tremelimumab 750 mg on day 1 of cycles 2-6 and then every 12 weeks until week 45
Receives: Drug: Tremelimumab; Drug: Paclitaxel
Tremelimumab+Durvalumab (B)ExperimentalArm B: * paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6 * tremelimumab 300 mg once on day 1 of cycle 2 * durvalumab 1500 mg on day 1 of cycles 2-12, every four weeks (until week 49)
Receives: Drug: Tremelimumab; Drug: Durvalumab; Drug: Paclitaxel
Tremelimumab without paclitaxel (C)ExperimentalArm C (control arm): • tremelimumab 750 mg on day 1 of cycles 1-5 and then every 12 weeks until week 41
Receives: Drug: Tremelimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall response rate (ORR), defined as the proportion of participants whose confirmed best overall response is either a PR or CR after treatment with paclitaxel and a high dose of tremelimumab based upon the RECIST v1.1 guidelines.

    Tumor evaluation will take place using CT-Chest and abdomen, based on the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) guidelines. The first evaluation will take place 12 weeks after initiating treatment. After this initial scan, tumor evaluation will take place every 8 weeks for the first year. After the first year, tumor evaluation will be done every 12 weeks.

    Measured: Final ORR will be determined after the confirmatory scan of the last patient, which is scheduled up to 21 weeks after start of treatment of the final patient

  2. Overall response rate (ORR), defined as the proportion of participants whose confirmed best overall response is either a PR or CR after treatment with paclitaxel, tremelimumab and durvalumab based upon the RECIST v1.1 guidelines.

    Tumor evaluation will take place using CT-Chest and abdomen, based on the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) guidelines. The first evaluation will take place 12 weeks after initiating treatment. After this initial scan, tumor evaluation will take place every 8 weeks for the first year. After the first year, tumor evaluation will be done every 12 weeks.

    Measured: Final ORR will be determined after the confirmatory scan of the last patient, which is scheduled up to 21 weeks after start of treatment of the final patient

Secondary outcomes (4)

  1. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

    Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

    Measured: Overall therapeutic safety will be determined 90 days after the last patient has received the last treatment dose

  2. Overall survival (OS) in months for each of the treatment strategies.

    survival data will be collected every 6 months after the last study visit for each participant.

    Measured: OS data will be collected up to 2 years after inclusion of the final patient

  3. Progression-free survival (PFS) in months for each of the treatment strategies

    survival data will be collected every 6 months after the last study visit for each participant.

    Measured: PFS data will be collected up to 2 years after inclusion of the final patient

  4. Duration of response in months for each of the treatment strategies

    survival data will be collected every 6 months after the last study visit for each participant.

    Measured: DOR data will be collected up to 2 years after inclusion of the final patient

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Mar 2019
  2. Study start1 May 2019
  3. Primary completion7 Sep 2023
  4. Study completion15 Jan 2025

Resources

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
A run-in safety phase will be followed by a non-comparative 3-arm randomized study with a Simon's 2-stage optimal design. Run-in safety phase will start with an increasing dose of tremelimumab in combination with paclitaxel. In the final part of the run-in safety phase, patients will be randomized to receive paclitaxel with either regular dose tremelimumab in combination with durvalumab, or a high dose tremelimumab. If no unexpected toxicity occurs, the experimental phase of the study will start, randomizing patients over 3 arms. The best arm will be expanded based on a Simon's 2-stage optimal design.
Masking
None (open label)
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03871036
Sponsor's protocol ID
M18ICR/ESR-18-13667
Acronym
ICRA
Status last verified
Mar 2025
First submitted
14 Feb 2019
Last updated
6 Mar 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Einerhand SMH, Ali H, Wong SQ, van Dorp J, van Maanen T, de Feijter JM, Montfoort MLV, Boellaard TN, Braaf LM, Brugman W, Vis DJ, Hollander CMJ, Daletzakis A, Schrijver HA, Snapper K, Oosting SF, Bruijnen CP, Wessels LFA, Chan KS, Suelmann BBM, van der Heijden MS. Tremelimumab with or without durvalumab in combination with paclitaxel in metastatic urothelial cancer: phase I/II ICRA trial. Nat Commun. 2026 Jun 17;17(1):7679. doi: 10.1038/s41467-026-74570-3.

    PubMed 42310313

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tremelimumab, Durvalumab and Paclitaxel in people with Urothelial Carcinoma, run by The Netherlands Cancer Institute at 1 site in Netherlands.

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 30 inclusion and 39 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 6 Mar 2025. 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 Netherlands. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Overall response rate (ORR), defined as the proportion of participants whose confirmed best overall response is either a PR or CR after treatment with paclitaxel and a high dose of tremelimumab based upon the RECIST v1.1 guidelines. (time frame: Final ORR will be determined after the confirmatory scan of the last patient, which is scheduled up to 21 weeks after start of treatment of the final patient). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03871036, which also lists 1 linked publication.

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 6 Mar 2025.

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