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Bladder Transitional Cell CarcinomaPhase 1(BLASST)-3NCT04972253

Phase I BLASST-3 Trial

A Phase 1 study testing Infigratinib in people with Bladder Transitional Cell Carcinoma and Bladder Cancer, run by Guru P. Sonpavde.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The aim of this research is to see whether using a drug that blocks a protein called FGFR (fibroblast growth factor receptor) prior to surgery is safe and effective in patients with bladder cancer that have mutations in FGFR3 or FGFR2 and who cannot receive chemotherapy with cisplatin prior to surgery The name of the… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Infigratinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
23 Dec 2021to Dec 2023
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

  • 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 (no safety data in pediatric patients is available for infigratinib).
  • 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
  • cT2-T4a N0 M0 disease after radiographic staging of chest, abdomen and pelvis, considered appropriate and planned for radical cystectomy as assessed by a Urologic Oncologist.
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  • Presence of the following FGFR3/2 activating alterations, as detected by either plasma or urine cfDNA or cfRNA or by tissue-based NGS (Predicine, Hayward, CA):
  • Mutations in exon 7 (R248C, S249C)
  • Mutations in exon 10 (G372C, A393E, Y375C)
  • Mutations in exon 15 (K652M/T, K652E/Q)
  • Any FGFR3/2 gene fusion (Availability of baseline archival tumor tissue for identification of FGFR3/2 alterations is not required, but tissue will be obtained when available including 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)
  • Ineligibility 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 he/she declines neoadjuvant cisplatin-based chemotherapy after specific informed consent describing the known benefits of cisplatin-based chemotherapy. The reason for cisplatin-ineligibility based on the above criteria or cisplatin refusal should be documented on the case report form.
  • 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)
  • 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) ≤1.5 x institutional upper limit of normal
  • Measured creatinine CL >30 mL/min or Calculated creatinine CL>30 mL/min by the Cockcroft-Gault formula 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 agespecific 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).
  • Patient has ability and willingness to sign a written informed consent document and 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

  • 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
  • Any prior participation in a study involving an FGFR inhibitor.
  • Concurrent enrolment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study
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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)
  • 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 currently receiving treatment with drugs that are known to be strong CYP3A4 inducers or inhibitors, including anti-epileptic drugs.
  • Use of medications that are known to prolong the QT interval and/or associated with a risk of torsade de pointes 7 days prior to the first dose of infigratinib.
  • Use of amiodarone within 90 days prior to first dose of infigratinib.
  • Use of medications that increase serum levels of calcium and/or phosphorus.
  • Concurrent use of warfarin or other coumadin-derivative anticoagulants; heparin and/or low molecular-weight heparins are permitted.
  • Inorganic phosphorus and/or total/ionized serum calcium outside normal limits prior to study entry.
  • Have clinically significant cardiac disease, including any of the following:
  • New York Heart Association (NYHA) Class ≥2B; subjects with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the NYHA classification.
  • Presence of Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade ≥2 ventricular arrhythmias, atrial fibrillation, bradycardia, or conduction abnormality
  • Unstable angina pectoris or acute myocardial infarction ≤3 months prior to first dose of study drug
  • QTcF >470 msec (males and females). Note: If the QTcF is >470 msec in the first ECG, a total of 3 ECGs separated by at least 5 minutes should be performed. If the average of these 3 consecutive results for QTcF is ≤470 msec, the subject meets eligibility in this regard
  • Known history of congenital long QT syndrome.
  • 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 infigratinib. NB: local surgery of isolated lesions for palliative intent is acceptable.
  • History of allogeneic organ transplantation
  • Current evidence of corneal or retinal disorder/keratopathy
  • 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
  • Female patients who are pregnant or breastfeeding, or patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of infigratinib monotherapy.
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
  • Inability to swallow oral medications
  • Judgement 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.

About this study

Official title: Biomarker-directed Neoadjuvant Therapy for Cisplatin-ineligible or Cisplatin-refusing Muscle-invasive Bladder Cancer: Phase I Bladder Cancer Signal Seeking Trial

The aim of this research is to see whether using a drug that blocks a protein called FGFR (fibroblast growth factor receptor) prior to surgery is safe and effective in patients with bladder cancer that have mutations in FGFR3 or FGFR2 and who cannot receive chemotherapy with cisplatin prior to surgery

The name of the study drug involved in this study is:

  • Infigratinib
Read the detailed description

This is a single-center (DF/HCC) prospective feasibility study to assess biomarker-directed neoadjuvant therapy in patients with cT2-T4aN0 MIBC who are candidates for radical cystectomy (RC) and ineligible for, or refuse, cisplatin-based neoadjuvant chemotherapy (NAC).

This research study involves using a drug that inhibits FGFR in patients with bladder cancer (that have mutations in FGFR) prior to surgery.

The name of the study drug involved in this study is:

  • Infigratinib

The research study procedures include pre-screening for eligibility and study treatment including evaluations and follow up visits. This pre-screening is already done as clinical care. Study participants will receive study treatment for 2 months prior to surgery and will be followed for at least 1 year after undergoing surgery.

It is expected that about 12 people will take part in this research study.

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

This research study is also a Feasibility Study, which is the first time investigators are examining this drug in patients with bladder cancer that has not spread to other organs. The U.S. Food and Drug Administration (FDA) has not approved infigratinib as a treatment for any disease.

Being tested
Infigratinib
Keywords
Bladder transitional cell carcinoma, Bladder Cancer, Fibroblast growth factor receptor
Medical subject headings
Urinary Bladder Neoplasms, Acrocephalosyndactylia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • InfigratinibDrug

    Also called BGJ-398

    Oral, dosage per protocol

Study groups in NCT04972253
Study groupRoleWhat they receive
InfigratinibExperimental* Infigratinib daily dosage per protocol 3-week on/1-week off schedule. 4 weeks will constitute 1 cycle of therapy. * Participants will receive 2 cycles (i.e. 8 weeks) and the treatment will be administered as an outpatient. * After completion of therapy, patients will undergo a CT of the chest, abdomen and pelvis (within 2 weeks of the last dose of therapy) and then proceed to Radical cystectomy 2-4 weeks after the last dose of therapy.
Receives: Drug: Infigratinib

What is being measured

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

  1. ≥ 70% of patients receiving at least 1 dose of study treatment followed by completion of radical cystectomy (Feasibility)

    Feasibility is defined as ≥ 70% of patients receiving at least 1 dose of study treatment followed by completion of radical cystectomy in the absence of DLT up to 4 weeks post-RC.

    Dose-limiting toxicities (DLTs) will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria). DLT will be defined as an adverse event (AE) or abnormal laboratory value deemed related to therapy with infigratinib, including those AEs and abnormal laboratory values that result in a failure to meet the criteria for re-treatment.

    Measured: time of first administration of study treatment until 4 weeks after RC up to 3 months

Secondary outcomes (4)

  1. Pathologic response (<ypT2N0) at time of RC.

    Pathologic response is defined as <pT2N0 disease at the time of RC (e.g. pT0N0, pT1N0, pTaN0, or pTisN0)

    Measured: 3 months

  2. Pathologic complete response (pCR) at time of RC.

    Pathologic complete response (pCR) is defined as achievement of pT0N0 disease at RC.

    Measured: 3 months

  3. Relapse-free survival (RFS) after RC.

    Relapse-free survival (RFS) is defined as the duration of time from time of RC to time of documented disease relapse or recurrence after RC, or death from any cause. Patients who have received at least one cycle of therapy and have undergone RC will be considered evaluable for RFS.

    Measured: 4 weeks after end of treatment, then every 12-24 weeks up to 1 year

  4. Progression-free proportion after neoadjuvant infigratinib, prior to RC

    Progression prior to RC will be defined as radiologic progression by RECIST 1.1 with development of radiologic T4b and/or N1/N2/N3 and/or or M1 disease (per RECIST 1.1) in scans obtained after commencement of neoadjuvant therapy and prior to RC

    Measured: 2 months

Timeline

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

  1. First posted22 Jul 2021
  2. Study start23 Dec 2021
  3. Primary completionDec 2022 (estimated)
  4. Study completionDec 2023 (estimated)

Why it stopped: Low Accrual

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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04972253
Sponsor's protocol ID
21-162
Acronym
(BLASST)-3
Status last verified
Aug 2022
First submitted
15 Jul 2021
Last updated
10 Aug 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 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 Infigratinib in people with Bladder Transitional Cell Carcinoma and Bladder Cancer, run by Guru P. Sonpavde.

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 32 inclusion and 33 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: withdrawn, as of the sponsor's last update on 10 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

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 withdrawn before enrolling participants, so there are no results.

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?

≥ 70% of patients receiving at least 1 dose of study treatment followed by completion of radical cystectomy (Feasibility) (time frame: time of first administration of study treatment until 4 weeks after RC up to 3 months). 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 NCT04972253.

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 10 Aug 2022.

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