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

NCT03762122 | Terminated Phase 2 DMC

• 1 other identifier: SAKK 19/18
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 11

Brief Summary

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.

Conditions

Squamous-cell Non-small Cell Lung Cancer

Keywords

Fibroblast growth factor receptor (FGFR); Rogaratinib; Advanced pretreated squamous-cell non-small cell lung cancer; SQCLC; FGFR mRNA

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) at 6 months

  at 6 months

Secondary Outcomes (4)

• Objective response (OR)

  At the end of trial treatment, expected at the latest after 4 years.

• Progression-free survival (PFS)

  From registration until disease progression according to the RECIST v1.1 criteria or death due to any cause whichever occurs first, up to 4 years.

• Overall survival (OS)

  From registration until death due to any cause, up to 4 years.

• Adverse events (AEs)

  At the end of trial treatment, expected at the latest after 4 years.

Study Arms (1)

Rogaratinib

EXPERIMENTAL

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.

Drug: Rogaratinib

Interventions

Rogaratinib DRUG

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

Also known as: BAY 1163877

Rogaratinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent according to Swiss law and ICH-GCP regulations before registration and prior to any trial specific procedures including screening procedures. Informed consent for trial entry must be offered only after positive results of individual FGFR testing has been received.
• Histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC (from inoperable stage IIIB to stage IV according to the 8th edition of the American Joint Commission on Cancer TNM staging system) with squamous-cell or predominantly squamous-cell histology (referred to SQCLC).
• Archival or fresh tumor biopsy specimen for FGFR (subtypes 1-3) mRNA expression testing available. Acceptable samples include core needle biopsies for deep tumor tissue (minimum three cores) or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions.
• High FGFR1-3 mRNA expression levels based on central analysis of archival or fresh tumor biopsy specimen (high expression defined as ≥ 1 FGFR isoform with RNAscope score of 3 or 4).
• Measurable or evaluable disease (according to RECIST v1.1). Previously irradiated lesions should not be counted as target lesions unless there has been demonstrated progression in the lesion since radiotherapy before enrolment and no other lesions are available for selection as target lesions.
• Patient failed standard systemic therapy for locally advanced or metastatic disease (1-3 prior chemotherapy regimens and at least 1 immune checkpoint inhibitor (combination allowed)).
• Patients with known brain metastases must have undergone definitive treatment (surgery and/or radiation) at least 2 weeks prior to registration and must be clinically stable (no requirement of steroids and no worsening neurological deficits for 2 weeks prior registration).
• Patients with a prior malignancy and treated with curative intention are eligible if treatment of that malignancy was completed at least 2 years before registration and the patient has no evidence of disease at registration. Less than 2 years is acceptable for malignancies with low risk of recurrence and/or no late recurrence.
• Known human immunodeficiency virus (HIV)-infected patients who are healthy and have a low risk of AIDS-related outcomes are eligible, if,
• CD4+ T-cell counts are ≥ 350 cells/ųL
• No history of AIDS-defining opportunistic infection within past 12 months
• Patient agrees to concomitant antiretroviral therapy (ART) if not currently on ART, or is on ART for ˃ 4 weeks and has a HIV viral load ˂ 400 copies/mL.
• Age ≥ 18 years.
• WHO performance status 0-2.
• Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L1, platelet count ≥ 100 x 109/L2, hemoglobin ≥ 90 g/L2

You may not qualify if:

• Symptomatic untreated brain metastases or leptomeningeal disease.
• Previous treatment with anti-FGFR directed therapies (e.g. receptor tyrosine kinase inhibitors including rogaratinib or FGFR-specific antibodies).
• Chemotherapy, or radiotherapy, or immunotherapy, or small molecule drugs within 3 weeks (1 week for palliative radiotherapy) prior to registration.
• Other investigational medicinal products within 4 weeks prior registration.
• Major surgery within 2 weeks prior registration.
• Concomitant use of other anti-cancer drugs or radiotherapy except for local pain control.
• Concomitant therapies that are known to increase serum phosphate levels (i.e. antacids, laxatives oral/rectal, oral phosphate binders, potassium phosphate) and that cannot be discontinued or switched to a different medication before trial entry.
• Use of strong inhibitors of CYP3A4 and strong inducers of CYP3A4 within 2 weeks prior registration or during trial treatment.
• History or current condition of an uncontrolled cardiovascular disease including any of the following conditions:
• Congestive heart failure (CHF) NYHA Class 2 or greater, unstable angina (symptoms of angina at rest).
• New-onset angina (within last 3 months prior registration).
• Myocardial infarction (MI) within past 6 months prior registration.
• Unstable cardiac arrhythmias requiring anti-arrhythmic therapy. Patients with arrhythmia not requiring therapy or under control with anti-arrhythmic therapy are eligible.
• Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
• Symptomatic arterial hypotension.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (11)

Kantonsspital Baden

Baden, 5404, Switzerland

Location

Universitaetsspital Basel

Basel, 4031, Switzerland

Location

IOSI Ospedale Regionale di Bellinzona e Valli

Bellinzona, 6500, Switzerland

Location

Inselspital Bern

Bern, 3010, Switzerland

Location

Kantonsspital Baselland Bruderholz

Bruderholz, 4101, Switzerland

Location

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Hopital Fribourgeois HFR

Fribourg, 1708, Switzerland

Location

Hôpitaux Universitaires de Genève

Geneva, 1211, Switzerland

Location

Kantonsspital Baselland

Liestal, 4410, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Kantonsspital Winterthur

Winterthur, CH-8401, Switzerland

Location

MeSH Terms

Conditions

Acrocephalosyndactylia

Interventions

Rogaratinib

Condition Hierarchy (Ancestors)

Craniosynostoses; Synostosis; Dysostoses; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Syndactyly; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Limb Deformities, Congenital; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Alfredo Addeo, MD

  University Hospital, Geneva

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 30, 2018
• First Posted: December 3, 2018
• Study Start: July 25, 2019
• Primary Completion: August 13, 2021
• Study Completion: August 24, 2021
• Last Updated: November 9, 2022

Record last verified: 2022-11

Locations

CH (11)