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Non-Transitional Cell Carcinoma of the Urothelial TractPhase 2NCT03430895

Evaluating Immune Therapy, Durvalumab (MEDI4736) With Tremelimumab for Metastatic, Non-transitional Cell Carcinoma of the Urinary Tract

A Phase 2 study testing durvalumab and tremelimumab in people with Non-Transitional Cell Carcinoma of the Urothelial Tract and Small Cell of the Bladder, run by Memorial Sloan Kettering Cancer Center at 4 sites in United States.

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 study is being done test to test the safety and effectiveness of durvalumab combined with tremelimumab in patients who have a rare form of cancer of the urinary tract. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
durvalumab and tremelimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
4 sitesUnited States
Study dates
31 Jan 2018to 10 Feb 2021
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

  • Age ≥ 18 years at time of informed consent
  • Body weight > 30 kg
  • Histologically or cytologically confirmed small cell carcinoma, squamous cell carcinoma or adenocarcinoma (confirmed at MSKCC) of the bladder, ureter, urethra, urachus, or renal pelvis. Patients with squamous cell carcinoma and adenocarcinoma are required to have a predominant squamous or adenocarcinoma component as reviewed by the pathologist at MSKCC. However, if any element of small cell or neuroendocrine differentiation is present, the patients will be classified as small cell/neuroendocrine.
  • Confirmation of availability of sufficient tissue from a prior surgery for correlative studies is required prior to enrollment. Patients must have representative non-TCC or the urothelial tract FFPE archival tumor specimens (tumor blocks or 30 unstained slides; preference for tumor blocks). These samples may be submitted between the time of consent and the start of treatment. Patients with < 30 slides may be enrolled after discussion with the principal or co-principal investigators.
  • Clinical evidence of metastatic (T4b, any N; any T, N2-3; M1) disease.
  • Life expectancy of 12 weeks of greater based on assessment by the treating investigator.
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  • Evidence of measurable disease by RECIST 1.1.
  • Patients with small cell carcinoma must have progressed after at least one prior systemic therapy. Patients with squamous cell carcinoma or adenocarcinoma may be previously untreated or have progressed after prior systemic therapy. Chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen. NOTE: There is no maximum number of prior treatments allowed.
  • Patients with brain metastases are allowed onto the study as long as patients have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic. Subjects with neurological symptoms should undergo a head CT scan or brain MRI to exclude brain metastasis, at the discretion of the treating physician.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  • Adequate normal organ and marrow function as defined below:
  • Hemoglobin ≥ 9.0 g/dL
  • Absolute neutrophil count (ANC) ≥ 1.0 x 109/L (> 1000 per mm^3)
  • Platelet count ≥ 100 x 109/L (>100,000 per mm^3)
  • Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (≤ 3 x institutional ULN in patients with Gilbert"s syndrome)
  • AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional ULN unless liver metastases are present, in which case it must be ≤ 5 x ULN
  • Calculated creatinine clearance > 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 serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
  • Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have 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 if they have been amenorrheic 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).
  • Female patients of reproductive potential and non-sterilized males who are sexually active with a female partner of childbearing potential must be willing to adhere to the following restrictions:
  • Females of reproductive potential who are sexually active with a non-sterilized male partner must agree to use at least 1 highly effective method of contraception (Table 3) from the time of screening until 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy. Cessation of birth control after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. It is strongly recommended that non-sterilized male partners of a female patient must use male condom plus spermicide throughout this period. Not engaging in sexual activity for the total duration of the drug treatment and the drug washout period is an acceptable practice.
  • Non-sterilized males who are sexually active with a female partner of childbearing potential must use a male condom plus spermicide from screening through 180 days after receipt of the final dose of durvalumab + tremelimumab combination therapy or 90 days after receipt of the final dose of durvalumab monotherapy. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Not engaging in sexual activity is an acceptable practice. Male patients should refrain from sperm donation throughout this period. It is strongly recommended that female partners (of childbearing potential) of male patients to also use a highly effective method of contraception throughout this period.
  • Highly effective methods of contraception, defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly.
  • Subject 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.

Who cannot join

  • Previous enrollment in the present study
  • Participation in another clinical study with an investigational product during the last 14 days
  • Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia"s Correction
  • Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA-4, including tremelimumab
  • Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) < 21 days prior to enrollment.
  • Major surgery within 28 days of starting study treatment. There is no minimum time requirement for minor procedures such as biopsy or vascular access placement.
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  • Radiation within 14 days of starting study treatment
  • 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)
  • Any unresolved toxicity from previous anti-cancer therapy must have resolved to at least ≤ Grade 1 (or baseline) at time of enrollment.
  • Patients with irreversible toxicity that is not reasonably expected to be exacerbated by treatment with durvalumab and tremelimumab may be included after consultation with the Principal Investigator or Co-Principal Investigator (e.g. alopecia, hearing loss, peripheral neuropathy).
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis, celiac disease, 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 (eg, following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that does not require systemic therapy
  • Patients without active autoimmune disease in the last 5 years may be included but only after consultation with the study physician
  • Patients with diverticulosis
  • Patients with celiac disease controlled by diet alone
  • History of primary immunodeficiency
  • History of allogeneic organ transplant
  • History of hypersensitivity to durvalumab, tremelimumab or any excipient
  • 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.
  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), 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.
  • History of leptomeningeal carcinomatosis
  • Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab or tremelimumab. Inactivated vaccines, such as the injectable influenza vaccine, are permitted.
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
  • Malignancies other than the disease under study within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g. prostate cancer with Gleason score ≤ 6, and prostate-specific antigen [PSA] ≤ 10 mg/mL, etc).
  • Patients should agree to not donate blood while participating in this study or for at least 90 days following the last infusion of durvalumab or tremelimumab
  • 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 90 days after the last dose of durvalumab monotherapy or180 days after the last dose of durvalumab + tremelimumab combination therapy.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Memorial Sloan Kettering Basking Ridge

    Basking Ridge, New Jersey, 07920

  • Memorial Sloan Kettering Commack

    Commack, New York, 11725

  • Memoral Sloan Kettering Westchester

    Harrison, New York, 10604

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase II Trial of Durvalumab (MEDI4736) and Tremelimumab in Metastatic, Non-transitional Cell Carcinoma of the Urothelial Tract

This study is being done test to test the safety and effectiveness of durvalumab combined with tremelimumab in patients who have a rare form of cancer of the urinary tract.

Being tested
durvalumab and tremelimumab
Keywords
Durvalumab (MEDI4736), Tremelimumab, immunotherapy, 17-511
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.

  • durvalumab and tremelimumabDrug

    Patients will receive durvalumab 1500 mg and tremelimumab 75 mg IV Q4W for up to 4 doses/cycles, then durvalumab 1500 mg Q4W starting 4 weeks after the last combination treatment for up to 9 doses.

Study groups in NCT03430895
Study groupRoleWhat they receive
combination of durvalumab and tremelimumabExperimentalPatients will receive durvalumab 1500 mg and tremelimumab 75 mg IV Q4W for up to 4 doses/cycles, then durvalumab 1500 mg Q4W starting at Week 16 for 9 doses (total treatment duration of 12 months).
Receives: Drug: durvalumab and tremelimumab

What is being measured

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

  1. Overall Response Rate

    by RECIST 1.1

    Measured: 2 years

Timeline

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

  1. First posted13 Feb 2018
  2. Study start31 Jan 2018
  3. Primary completion10 Feb 2021
  4. Study completion10 Feb 2021

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
This is a single-arm, phase II study with a Simon minimax design testing the combination of durvalumab and tremelimumab in patients with non-TCC of the urothelial tract.
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03430895
Sponsor's protocol ID
17-511
Status last verified
Feb 2021
First submitted
7 Feb 2018
Last updated
1 Dec 2021
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing durvalumab and tremelimumab in people with Non-Transitional Cell Carcinoma of the Urothelial Tract and Small Cell of the Bladder, run by Memorial Sloan Kettering Cancer Center at 4 sites 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 31 inclusion and 31 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 1 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites 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 1 Dec 2021). 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?

Overall Response Rate (time frame: 2 years). 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 NCT03430895.

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 1 Dec 2021.

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