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Muscle Invasive Bladder CancerPhase 1NCT03773666

A Feasibility Study of Durvalumab +/- Oleclumab as Neoadjuvant Therapy for Muscle-invasive Bladder Cancer (BLASST-2)

A Phase 1 study testing Durvalumab and Oleclumab in people with Muscle Invasive Bladder Cancer, run by Dana-Farber Cancer Institute at 2 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 research study is studying a new anti-cancer drug durvalumab (MEDI4736) with or without another new anti-cancer drug Oleclumab (MEDI9447) before surgery for bladder cancer. The drugs involved in this study are: Durvalumab (MEDI4736) Oleclumab (MEDI9447) Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Muscle Invasive Bladder Cancer
What is being tested?
Durvalumab and Oleclumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
2 sitesUnited States
Study dates
20 Feb 2019to 2 Aug 2021
Phase
Phase 1
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 must fulfil all of the following criteria: Written informed consent and any locally-required authorization (e.g. HIPAA) obtained from the patient prior to performing any protocol-related procedures, including screening evaluations
  • Age > 18 years at time of study entry
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (See Appendix A).
  • Histologically confirmed bladder transitional cell carcinoma (TCC)
  • ---Patients with mixed histology are required to have a component of TCC, and no component of small cell histology
  • T2-T4a N0 M0 disease, considered appropriate and planned for radical cystectomy
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  • Ineligible for cisplatin-based chemotherapy, defined by any of the following:
  • Creatinine clearance (CL) <60 mL/min. GFR should be calculated from serum/plasma creatinine using the Cockcroft-gault formula.
  • CTCAE v5.0 Grade > 1 hearing loss
  • CTCAE v5.0 Grade > 1 neuropathy
  • NYHA Class > II cardiac dysfunction
  • Patients not meeting the above criteria are eligible if she/he declines perioperative cisplatin-based chemotherapy after specific informed consent describing the known benefits of cisplatin-based chemotherapy.
  • Adequate organ function laboratory values as defined below:
  • Hemoglobin ≥ 9.0 g/dL
  • Absolute neutrophil count (ANC) 1.5 x (> 1500 per mm3)
  • Platelet count ≥100 x 109/L (>75,000 per mm3)
  • Albumin > 2.5 g/dL
  • International Normalized Ratio (INR) or activated partial thromboplastin time (aPTT) < 1.5 x ULN, unless the patient is receiving anticoagulation therapy provided INR or PTT is within the therapeutic range of the intended anticoagulant therapy.
  • Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN)
  • ---This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
  • AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal
  • Measured creatinine CL >30 mL/min or Calculated creatinine 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 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 postmenopausal 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 radiationinduced 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.
  • Availability of baseline archival tumor tissue obtained for correlative studies dated within 8 weeks of study registration.
  • Either FFPE tumor tissue block or a minimum of fifteen 5μm unstained FFPE slides and fifteen 10μm unstained FFPE slides with an associated pathology report is required.
  • Patients without adequate baseline tumor tissue or have archival tumor tissue >8 weeks from registration must undergo cystoscopic tumor biopsy, meeting the above tissue criteria.

Who cannot join

  • Patients with primary TCC of the ureter, urethra, or renal pelvis without TCC of the bladder
  • Inoperable tumor(s) with fixation to the pelvic wall on clinical exam
  • Any previous systemic chemotherapy or radiotherapy for TCC of bladder
  • Participation in another clinical study with an investigational product during the last 6 months
  • Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
  • Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
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  • History of another primary malignancy except for:
  • Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug 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 (e.g. cervical cancer in situ)
  • Receipt of the last dose of intravesical chemotherapy or biologic therapy
  • ≤ 42 days (6 weeks) prior to the first dose of study drug for patients who have received prior intravesical chemotherapy or biologic therapy (e.g. BCG)
  • Mean QT interval corrected for heart rate using Fridericia's formula (QTcF)
  • ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart) for durvalumab + oleclumab cohorts only. Patient safety and the cardiac EKG should be consulted as needed.
  • Any unresolved toxicity NCI CTCAE version 5.0 Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
  • Patients with Grade ≥2 neuropathy will be evaluated on a case-bycase basis after consultation with the Study Physician.
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab and/or oleclumab may be included only after consultation with the Study Physician.
  • Any concurrent chemotherapy, 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.
  • 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
  • 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 leptomeningeal carcinomatosis
  • Brain metastases or spinal cord compression. 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, 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.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of study drug. 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 durvalumab
  • + oleclumab or 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
  • Prior randomization or treatment in a previous durvalumab and/or oleclumab clinical study regardless of treatment arm assignment
  • Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02214

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: A Feasibility Study of Durvalumab (MEDI4736) Alone or in Combination With Oleclumab (MEDI9447) as Neoadjuvant Therapy for Muscle-invasive Bladder Cancer (BLASST-2)

This research study is studying a new anti-cancer drug durvalumab (MEDI4736) with or without another new anti-cancer drug Oleclumab (MEDI9447) before surgery for bladder cancer.

The drugs involved in this study are:

  • Durvalumab (MEDI4736)
  • Oleclumab (MEDI9447)
Read the detailed description

This research study is a Feasibility Study, which is the first time investigators are examining these drugs, Durvalumab (MEDI4736) and Oleclumab (MEDI9447) in patients with muscle-invasive bladder cancer (MIBC) cancer prior to surgery. Cisplatin-containing chemotherapy given before surgery is the standard of care in patients with MIBC because it increases the rate of cure after surgery. Participants may still be eligible for this study if their doctor determines that participants are able to receive cisplatin-containing chemotherapy, but the participants elect not to undergo chemotherapy before surgery, understanding the potential benefits of chemotherapy. The FDA (the U.S. Food and Drug Administration) has not approved Durvalumab (MEDI4736) for localized bladder cancer prior to surgery, but it has been approved for other uses, including for locally advanced or metastatic bladder cancer after progression on platinum-containing chemotherapy. The FDA (the U.S. Food and Drug Administration) has not approved Oleclumab (MEDI9447) as a treatment for any disease. Durvalumab is a monoclonal antibody (an antibody is a protein produced by the body's immune system) that works by blocking the Programmed Cell Death Ligand 1 (PD-L1), a protein on cancer cells that stops the body's immune system from killing cancer cells, to increase the body's immune response to prevent or slow down cancer growth. Oleclumab is a monoclonal antibody that works by reducing the amount of adenosine, a small molecule called a metabolite that binds to adenosine receptors on immune cells to regulate the immune system and suppress the immune response. Reducing the amount of immunosuppressive adenosine can increase the body's immune response to kill cancer cells. It is hoped that by combining Oleclumab with Durvalumab, an even greater immune response against the tumor will be generated. This research study is designed to see if the new anti-cancer drug Durvalumab (MEDI4736) with or without another new anti-cancer drug Oleclumab (MEDI9447) can be safely administered before surgery for bladder cancer

Being tested
Durvalumab, Oleclumab
Keywords
Bladder Cancer
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.

  • DurvalumabDrug

    Also called MEDI4736

    Durvalumab is a monoclonal antibody (an antibody is a protein produced by the body's immune system) that works by blocking the Programmed Cell Death Ligand 1 (PD-L1), a protein on cancer cells that stops the body's immune system from killing cancer cells.

  • OleclumabDrug

    Also called MEDI9447

    Oleclumab is a monoclonal antibody that works by reducing the amount of adenosine, a small molecule called a metabolite that binds to adenosine receptors on immune cells to regulate the immune system and suppress the immune response. Reducing the amount of immunosuppressive adenosine can increase the body's immune response to kill cancer cells.

Study groups in NCT03773666
Study groupRoleWhat they receive
DurvalumabExperimental-Durvalumab will be administered intravenously every 2 weeks, with 14 consecutive days defined as a treatment cycle
Receives: Drug: Durvalumab
Durvalumab + OleclumabExperimental* Durvalumab will be administered intravenously every 2 weeks, with 14 consecutive days defined as a treatment cycle * Oleclumab will be administered intravenously every 2 weeks, with 14 consecutive days defined as a treatment cycle
Receives: Drug: Durvalumab; Drug: Oleclumab

What is being measured

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

  1. Number of Participants Receiving at least One Dose of Study Therapy Followed by Surgery without Dose-Limiting Toxicity (DLT) up to Twelve Weeks Post-Radical Cystectomy (RC)

    Measured: 2 years

Secondary outcomes (3)

  1. Number of Participants Receiving at least One Cycle of Study Therapy and Undergone RC Having <pT2N0 Disease at Time of RC

    Measured: 2 years

  2. Duration of Time of RC to Time of Documented Disease Relapse or Recurrence after RC

    Measured: 2 years

  3. Radiographic Progression by RECIST 1.1 Criteria from Time of Baseline Screening Imaging to the End of Treatment Imaging Pre-RC

    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 posted12 Dec 2018
  2. Study start20 Feb 2019
  3. Primary completion4 Feb 2021
  4. Study completion2 Aug 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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03773666
Sponsor's protocol ID
18-507
Status last verified
Sep 2022
First submitted
8 Dec 2018
Last updated
13 Sep 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor-Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Durvalumab and Oleclumab in people with Muscle Invasive Bladder Cancer, run by Dana-Farber Cancer Institute at 2 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 33 inclusion and 41 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 13 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 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.

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?

Number of Participants Receiving at least One Dose of Study Therapy Followed by Surgery without Dose-Limiting Toxicity (DLT) up to Twelve Weeks Post-Radical Cystectomy (RC) (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 NCT03773666.

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 13 Sep 2022.

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