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Bladder CancerPhase 1NCT02925533

Ph 1B B-701 in Combination With Pembrolizumab in Metastatic Transitional Cell Carcinoma of the Urothelial Tract

A Phase 1 study testing B-701 and Pembrolizumab in people with Bladder Cancer, run by Mark Pomerantz, MD at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This research study is studying a combination of two experimental drugs as a possible treatment for Bladder Cancer that recurred after treatment with standard therapy, or Bladder Cancer that got worse while on treatment with standard therapy. Read more about this study

Who is it for?
Ages 18 to 18 years
Conditions the study is for
Bladder Cancer
What is being tested?
B-701 and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
14 Dec 2016to Jun 2017
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 to 18 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Participants must have Stage IV, locally advanced or metastatic (T4b, any N; or any T, N2-3) urothelial bladder cancer or transitional cell carcinoma (TCC) arising in another location of the urinary tract, including urethra, ureter, and renal pelvis. The diagnosis must be histologically or cytologically confirmed. Mixed histologies are permitted as long as TCC is the major component (i.e. > 50% of the pathologic specimen). Pure or predominant squamous cell carcinomas or adenocarcinomas are not permitted.
  • Relapsed after or refractory to one or two prior lines of chemotherapy for advanced or metastatic/recurrent disease (at least one cycle each) which have not included a PD-L1 or FGFR inhibitor. At least one regimen should have included a platinum agent unless contraindicated for the subject. Prior neoadjuvant or adjuvant chemotherapy (without a PD-L1 or FGFR inhibitor) is permitted and will not be counted as first-line chemotherapy, as long as the subject has not progressed within 12 months of the last dose. However, a regimen of neoadjuvant or adjuvant chemotherapy will be counted as first-line chemotherapy if the patient progressed within 12 months of the last dose.
  • Age ≥ 18 years
  • Eastern cooperative oncology group (ECOG) performance status ≤ 1 (Karnofsky ≥ 60%)
  • Participants must have normal organ and marrow function as defined below:
  • leukocytes ≥ 3000/mcL
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  • absolute neutrophil count ≥ 1500/mcL
  • platelets ≥ 75,000/mcL
  • hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
  • total bilirubin within normal institutional limits
  • EXCEPTION: Subjects with known Gilbert's disease: total bilirubin ≤ 3 × institutional upper limit of normal (ULN)
  • aspartate aminotransferase (AST) or serum glutamic oxaloacetic transaminase (SGOT)/Alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 × institutional ULN
  • EXCEPTION: Subjects with documented liver metastases: AST and/or ALT ≤ 5 × institutional ULN
  • creatinine within normal institutional limits OR
  • creatinine clearance ≥ 60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal (derived by the Cockcroft-Gault formula [Cockcroft 1976])
  • albumin ≥ 2.5 mg/dL
  • prothrombin time/international normalized ratio (PT/INR) and partial thromboplastin time (PTT) ≤ 1.5 × institutional ULN
  • Note: Screening labs should be performed within 10 days of treatment initiation.
  • Absence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule (such conditions should be discussed with the subject before study entry)
  • The effects of B-701 on the developing human fetus are unknown. For this reason and because PD-1 inhibitors such as pembrolizumab may potentially cause fetal harm, women of child-bearing potential (defined as those who have not been surgically sterilized or have not been free from menses for > 1 year) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of study drug administration.
  • Female of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medications. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Female of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study and through 4 months after the last dose of study medication.
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Participants who have had chemotherapy, targeted small molecule therapy, or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier.
  • Participants who are receiving, or have received, any other investigational drugs or devices within the 2 weeks prior to the first dose of study medications.
  • Participants who received major surgery must be recovered adequately from the toxicity and/or complications from the interventions prior to starting therapy.
  • Participants with a diagnosis of immunodeficiency or who are receiving systemic steroid therapy (>5 mg prednisone or its equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
  • Participants who have a primary central nervous system (CNS) malignancy, or untreated/active CNS metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control). Individuals with a history of treated CNS metastases are eligible, provided they meet all of the following criteria:
  • Evaluable or measurable disease outside the CNS
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  • Radiographic demonstration of stability upon the completion of CNS directed therapy and no evidence of interim progression (for at least 4 weeks prior to the first dose of study drug) between the completion of CNS-directed therapy and the screening radiographic procedure
  • The screening CNS radiographic procedure is ≥ 8 weeks since completion of radiotherapy and ≥ 4 weeks since the discontinuation of corticosteroids and anticonvulsants Note: These exceptions do not include carcinomatous meningitis which is excluded regardless of clinical stability.
  • Participants with a history of allergic reactions attributed to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
  • Participants with active autoimmune disease that has required systemic treatment (>5 mg of prednisone or its equivalent) in the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Participants with known evidence of active, non-infectious pneumonitis.
  • Participants with an active infection requiring systemic therapy.
  • Participants who have received a live vaccine within 30 days of planned start of study therapy.
  • Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
  • Participants who have had a prior anti-cancer monoclonal antibody (mAb) within 2 weeks prior to Cycle 1 Day 1 or who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 2 weeks earlier.
  • Participants unwilling or unable to discontinue use of prohibited therapies, including any cytotoxic chemotherapy, radiotherapy, immunotherapy or biologic agent (approved or investigational) for the treatment of TCC are ineligible.
  • Participants with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Participants who have undergone a major surgical procedure or trauma within 4 weeks prior to Cycle 1, Day 1. All wounds must be fully healed on Cycle 1, Day 1
  • Participants with a history of other malignancy which could affect compliance with the protocol or interpretation of results. Individuals with a history of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are allowed. Participants with a malignancy that has been treated with curative intent will also be allowed if the malignancy has been in remission without treatment for ≥ 2 years prior to Cycle 1, Day 1.
  • Pregnant women are excluded from this study because the risks with B-701 are unknown and pembrolizumab is a PD-1 inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with B-701 and pembrolizumab, breastfeeding should be discontinued. Women of child-bearing potential must agree to use adequate birth control throughout the study duration.
  • Hepatitis B, hepatitis C, and HIV serology-positive (or known history of HIV seropositive status) participants are ineligible because these underlying diseases will confound interpretation of important safety assessments, e.g. liver function tests, increased potential for reactivation or exacerbation of viral infections. Such individuals may be taking or require other drugs, and may be at higher risk of opportunistic infections and adverse effects. Hepatitis B, hepatitis C, and HIV serology-positive individuals were excluded from the pivotal pembrolizumab clinical trial in melanoma, so safety of this drug in this setting is unknown.
  • Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at screening or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to Cycle 1, Day 1
  • Has a known history of active TB (Bacillus Tuberculosis)
  • Participants who weigh > 110 kg will be ineligible due to study drug limitations

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: A Phase 1B Study of B-701 in Combination With Pembrolizumab in Relapsed or Refractory Locally Advanced or Metastatic Transitional Cell Carcinoma of the Urothelial Tract

This research study is studying a combination of two experimental drugs as a possible treatment for Bladder Cancer that recurred after treatment with standard therapy, or Bladder Cancer that got worse while on treatment with standard therapy.

The following interventions will be involved in this study:

  • B-701
  • Pembrolizumab
Read the detailed description

This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational intervention to use for further studies. "Investigational" means that the intervention is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved B-701 as a treatment for any disease.

The FDA has not approved Pembrolizumab for Bladder Cancer but it has been approved for other uses.

This is the first time that B-701 in combination with Pembrolizumab will be given to humans.

In this research study, Investigators are...

  • Testing the effectiveness and safety of the combination of two experimental drugs (B-701 and Pembrolizumab);
  • Learning about the good and/or bad effects the drugs have on participants and their cancer;
  • Administering B-701 and Pembrolizumab, which are antibodies (proteins that bind to other molecules), because...
  • B-701 binds to a protein receptor called FGFR3 (fibroblast growth factor receptor 3). FGFR3 has been found to be present (expressed) or changed (mutated) on the surface of in many types of cancer cells. Targeting FGFR3 may inhibit cancer growth.
  • Pembrolizumab binds to a protein cell surface receptor called PD-1, which is found on certain types of lymphocytes and which are also involved in many types of cancer;
  • Treating participants with Pembrolizumab, which is approved by the FDA for the treatment of Metastatic Melanoma, a Cancer of the skin;
  • Collecting blood and tissue samples and other related medical information to learn more about the development of cancer and predictors of response;
  • And hoping to learn how the combination of study drugs work in the treatment of cancer to help develop new treatments.
Conditions
Bladder Cancer
Being tested
B-701, Pembrolizumab
Keywords
Bladder Cancer, Urothelial 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.

  • B-701Drug

    B-701 is a phage-derived, affinity-matured, human monoclonal antibody (mAb) specific for FGFR3. It is based on a human immunoglobulin G1 (IgG1) framework containing heavy chain VHIII and light chain VκI subgroup sequences.

  • PembrolizumabDrug

    Also called Keytruda, MK-3475

    Pembrolizumab is an mAb that binds to the programmed cell death protein 1 (PD-1) receptor and blocks its interaction with programmed death-ligand 1 (PD-L1) and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth.

Study groups in NCT02925533
Study groupRoleWhat they receive
B-701 and PembrolizumabExperimental* B-701 will be administered every 3 weeks intravenously * Pembrolizumab will be administered every 3 weeks intravenously
Receives: Drug: B-701; Drug: Pembrolizumab

What is being measured

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

  1. Preliminarily Evaluate The Safety Of B-701 In Combination With Pembrolizumab For The Treatment Of TCC

    Safety will be assessed through summaries of AEs (adverse events), changes in laboratory test results, ECGs (electrocardiograms), and changes in vital signs

    Measured: 2 years

Secondary outcomes (1)

  1. To Assess The Efficacy Of B-701 In Combination With Pembrolizumab For The Treatment Of TCC

    Measured by RECIST-based assessment of response and progression

    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 posted6 Oct 2016 (estimated)
  2. Study start14 Dec 2016
  3. Primary completionJun 2017
  4. Study completionJun 2017

Why it stopped: Terminated due to safety concerns.

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02925533
Sponsor's protocol ID
16-246
Status last verified
Jun 2017
First submitted
4 Oct 2016
Last updated
27 Jun 2017
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing B-701 and Pembrolizumab in people with Bladder Cancer, run by Mark Pomerantz, MD at 1 site 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 23 inclusion and 24 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: stopped early, as of the sponsor's last update on 27 Jun 2017. 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 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 was stopped early (reason given: Terminated due to safety concerns.). Results are not available in the source record.

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?

Preliminarily Evaluate The Safety Of B-701 In Combination With Pembrolizumab For The Treatment Of TCC (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 NCT02925533.

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 27 Jun 2017.

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