Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

All Drugs and Chemicals

Mitogens

Rogaratinib is given at a dose of 600 mg twice daily in continuous 28-days cycles, without treatment breaks (except for toxicity management). Trial treatment is continued until evidence of tumor progression, unacceptable toxicity, consent withdrawal or withdrawal by the investigator.

Rogaratinib (BAY 1163877; Bayer) is an oral pan-kinase inhibitor, which selectively inhibits FGFR1, FGFR2, FGFR3, and FGFR4.

Rogaratinib

Alfredo Addeo, MD

A recent investigation showed that a substantial proportion of patients with SQCLC (46%) exhibit tumor overexpression of fibroblast growth factor receptor (FGFR) messenger ribonucleic acid (mRNA) and are potentially sensitive to FGFR-targeting treatment. Rogaratinib is a novel pan-FGFR inhibitor which showed strong anti-tumor efficacy in pre-clinical models as a single agent in FGFR pathway-addicted tumor models. SQCLC patients overexpressing tumor FGFR mRNA, who will be included into this clinical trial, do not have currently any alternative systemic treatment with a proven and clinically reasonable benefit.

The objective of the trial is to determine clinical activity and safety of rogaratinib in patients with advanced SQCLC overexpressing tumor FGFR1-3 mRNA.

Squamous-cell lung cancer (SQCLC) is a distinct histologic subtype of non-small cell lung cancer (NSCLC) that is challenging to treat because of specific clinicopathologic characteristics (older age, advanced disease at diagnosis, central location of tumors) and the absence of molecular alterations, which can be successfully treated with targeted therapy. A recent investigation showed that a substantial proportion of patients with SQCLC (46%) exhibit tumor overexpression of fibroblast growth factor receptor (FGFR) messenger ribonucleic acid (mRNA) and are potentially sensitive to FGFR-targeting treatment.

Rogaratinib is a novel pan-FGFR inhibitor which showed strong anti-tumor efficacy in pre-clinical models as a single agent in FGFR pathway-addicted tumor models. The clinical experience with rogaratinib comes from two ongoing phase I trials enrolling patients with refractory, locally advanced or metastatic solid tumors who were selected based on tumoral overexpression of FGFR mRNA. Such selection identifies patients with high FGFR tumor target levels due to DNA aberrations in FGFR-encoding genes and due to non-genetic and epigenetic regulation of FGFR expression (incl. promoter activation). To date, rogaratinib has shown to be well tolerated (no dose-limiting toxicity) with promising clinical activity, in particular in bladder cancer.

Despite the constant improvement in the treatment of patients with advanced lung cancer, there is still a high-unmet medical need to develop new and highly active anticancer drugs for patients who have failed standard systemic treatment, and have an otherwise very unfavorable prognosis. SQCLC patients overexpressing tumor FGFR mRNA, who will be included into this clinical trial, do not have currently any alternative systemic treatment with a proven and clinically reasonable benefit.

The objective of the trial is to determine clinical activity and safety of rogaratinib in patients with advanced SQCLC overexpressing tumor FGFR1-3 mRNA.

This is a single-arm, multicenter phase II clinical trial. The trial uses a single-stage design based on a time-to-event rate to a specific time-point using Kaplan-Meier estimators.

Rogaratinib is given at a dose of 800 mg twice daily in continuous 28-days cycles, without treatment breaks (except for toxicity management). Trial treatment is continued until evidence of tumor progression, unacceptable toxicity, consent withdrawal or withdrawal by the investigator.

In order to include 24 patients into the trial, it is expected that 52 patients with advanced SQCLC have to be screened for tumor FGFR mRNA overexpression. Taking into account patients who are FGFR mRNA positive but cannot be enrolled (attrition rate of 20%), it is estimated that 68 patients will have to be screened in total.

Rogaratinib in Patients With Advanced Pretreated Squamous-cell Non-small Cell Lung Cancer (SQCLC)

Fibroblast Growth Factor Receptor (FGFR) Inhibitor Rogaratinib in Patients With Advanced Pretreated Squamous-cell Non-small Cell Lung Cancer (SQCLC) Overexpressing FGFR mRNA. A Multicenter, Single Arm Phase II Trial

OR is defined as complete response (CR) or partial response (PR) achieved by the patient during trial treatment. Tumor response will be evaluated according to RECIST v1.1 criteria.

Patients without any tumor assessment during trial treatment will be regarded as having a non-evaluable response (NE) and shall be considered as failures for this endpoint

PFS is defined as the time from registration until disease progression according to the RECIST v1.1 criteria or death due to any cause, whichever occurs first.

Patients not experiencing an event at the time of the analysis, as well as patients starting a subsequent anticancer treatment in the absence of an event, will be censored at the date of their last available tumor assessment showing no evidence of progression before starting a subsequent anticancer treatment, if any.

OS is defined as the time from registration until death due to any cause. Patients not experiencing an event will be censored at the last date they were known to be alive.

All AEs will be assessed according to NCI CTCAE v5.0

Swiss Group for Clinical Cancer Research

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Urinary Bladder Neoplasms

Non-Muscle Invasive Bladder Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

BCG Vaccine

* Rogaratinib is administered orally twice daily
* Rogaratinib is held for 72 hours before cystoscopy/TURBT and if no complications are seen, treatment is resumed 24 hours after the TURBT

Rogaratinib is an oral drug that inhibits FGFR. Mutations in FGFR help bladder cancer grow.

Bradley A. McGregor, MD

This research study is studying the safety, tolerability, and tumor activity of the study drug known as rogaratinib as a possible treatment for bladder cancer.

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied. The U.S. Food and Drug Administration (FDA) has not approved rogaratinib as a treatment for any disease.

In this research study, the investigators are studying rogaratinib in bladder cancer that has not responded to BCG and overexpresses a protein called FGFR1 or 3.

* Mutations in FGFR help bladder cancer grow. In metastatic cancers that express FGFR 1 or 3, rogaratinib and other inhibitors of FGFR have shown to be an effective treatment
* Rogaratinib is an oral drug that inhibits FGFR
* To date, no therapy has been shown to be effective in controlling bladder cancer after BCG does not work.

Rogaratinib for BCG Refractory High Risk Non-Muscle Invasive Bladder Cancer With FGFR1/2 Overexpression

Phase II Clinical Trial of Rogaratinib for High Risk Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus Calmette-Guerin (BCG) With FGFR1 or FGFR3 Gene Overexpression: The Bladder Cancer Signal Seeking Trial (BLASST)-3

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

Absence of any cancer in the bladder (No carcinoma in situ or new lesions) on examination with TURBT

Duration of time from study entry until appearance of any cancer in the bladder (No carcinoma in situ or new lesions) on examination with TURBT

Percentage of patients with a side effect from rogaritinib while on study

Bayer

Dana-Farber Cancer Institute

Principal Investigator

Digestive System Diseases

Nervous System Diseases

Heart and Blood Diseases

Symptoms and General Pathology

Wounds and Injuries

Skin and Connective Tissue Diseases

Rare Diseases

Sarcoma

Gastrointestinal Stromal Tumors

Hematoma, Subdural

Neoplasms, Connective and Soft Tissue

Neoplasms, Connective Tissue

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Soft Tissue Sarcoma

Patients receive rogaratinib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy at baseline and progression and CT, MRI, and PET-CT every 8 weeks. Patients may also undergo blood sample collection on study.

Biopsy

Biospecimen Collection

Computed Tomography

Magnetic Resonance Imaging

Positron Emission Tomography

Suzanne George

This phase II trial studies the effect of rogaratinib in treating patients with sarcoma with a change in a group of proteins called fibroblast growth factor receptors (FGFRs) or SDH-deficient gastrointestinal stromal tumor (GIST). Rogaratinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVE:

I. To estimate the objective radiographic response rate to single agent rogaratinib (BAY 1163877) in two cohorts of patients with sarcoma: Cohort A defined as patients with a sarcoma which harbors an alteration in fibroblast growth factor receptor (FGFR) 1, 2, 3 or 4 identified by next-generation sequencing profiling, and Cohort B defined as patients with advanced succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST).

SECONDARY OBJECTIVES:

I. To estimate progression-free survival (PFS) in patients in Cohort A and Cohort B treated with rogaratinib (BAY 1163877).

II. Further assessment for safety and tolerability.

EXPLORATORY OBJECTIVES:

I. To evaluate serial measurements of FGFR and FGFR ligand in serial tumor biopsies as potential pharmacodynamic markers of FGFR pathway inhibition by ribonucleic acid sequencing (RNA-seq) (pre-treatment biopsy and post-progression biopsy \[if available\]).

II. Whole exome sequencing (WES) of the pre-treatment biopsy and post-progression biopsy (if available) to help identify mechanisms of resistance.

III. To bank tumor material, germline deoxyribonucleic acid (DNA), and peripheral blood for potential future research for participating subjects who provide additional consent.

IV. To explore rogaratinib exposure with pharmacodynamics effects (i.e., clinical response, toxicity, and markers of FGFR pathway inhibition).

OUTLINE:

Patients receive rogaratinib orally (PO) twice daily (BID) on days 1-28 of each cycle. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy at baseline and progression and computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)-CT every 8 weeks. Patients may also undergo blood sample collection on study.

After completion of study treatment, patients are followed up at 30 days.

Testing the Anti-cancer Drug, Rogaratinib (BAY 1163877), for Treatment of Advanced Sarcoma With Alteration in Fibroblast Growth Factor Receptor (FGFR 1-4), and in Patients With SDH-deficient Gastrointestinal Stromal Tumor (GIST)

Phase 2 Study of Rogaratinib (BAY 1163877) in the Treatment of Patients With Sarcoma Harboring Alterations in Fibroblast Growth Factor Receptor (FGFR) 1-4 and SDH-Deficient Gastrointestinal Stromal Tumor (GIST)

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Will be evaluated in serial tumor biopsies as potential pharmacodynamic markers of FGFR pathway inhibition by ribonucleic acid sequencing. Estimation of continuous biomarker measures will be via mean or median as appropriate and standard deviation.

Will identify mechanisms of resistance via whole exome sequencing of pre- and post-treatment biopsies and considered exploratory.

The duration of overall response is measured from the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

Will be estimated using Kaplan-Meier method.

Adverse events will be measured by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Rogaratinib in Patients With Advanced Pretreated Squamous-cell Non-small Cell Lung Cancer (SQCLC)	NCT03762122	Squamous-cell N...	Rogaratinib	18 Years -	Swiss Group for Clinical Cancer Research
Rogaratinib for BCG Refractory High Risk Non-Muscle Invasive Bladder Cancer With FGFR1/2 Overexpression	NCT04040725	Bladder Cancer	Rogaratinib	18 Years -	Dana-Farber Cancer Institute
Rogaratinib for BCG Refractory High Risk Non-Muscle Invasive Bladder Cancer With FGFR1/2 Overexpression	NCT04040725	Bladder Cancer	Rogaratinib	18 Years -	Dana-Farber Cancer Institute
Testing the Anti-cancer Drug, Rogaratinib (BAY 1163877), for Treatment of Advanced Sarcoma With Alteration in Fibroblast Growth Factor Receptor (FGFR 1-4), and in Patients With SDH-deficient Gastrointestinal Stromal Tumor (GIST)	NCT04595747	Locally Advance... Locally Advance... Metastatic Gast... Metastatic Sarc... Stage III Gastr... Stage III Small... Stage IV Gastri... Stage IV Small ...	Biopsy Biospecimen Col... Computed Tomogr... Magnetic Resona... Positron Emissi... Rogaratinib	18 Years -	National Cancer Institute (NCI)
Rogaratinib for BCG Refractory High Risk Non-Muscle Invasive Bladder Cancer With FGFR1/2 Overexpression	NCT04040725	Bladder Cancer	Rogaratinib	18 Years -	Dana-Farber Cancer Institute
Rogaratinib in Patients With Advanced Pretreated Squamous-cell Non-small Cell Lung Cancer (SQCLC)	NCT03762122	Squamous-cell N...	Rogaratinib	18 Years -	Swiss Group for Clinical Cancer Research
Rogaratinib in Patients With Advanced Pretreated Squamous-cell Non-small Cell Lung Cancer (SQCLC)	NCT03762122	Squamous-cell N...	Rogaratinib	18 Years -	Swiss Group for Clinical Cancer Research

Spots Global Cancer Trial Database for rogaratinib

Every month we try and update this database with for rogaratinib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for rogaratinib

Every month we try and update this database with for rogaratinib cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for rogaratinib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.