Rogaratinib, Palbociclib y Fulvestrant in Patients With Breast Cancer.

NCT04483505 | Completed Phase 1

• 2 other identifiers: ROGABREAST2020-000055-12
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 8

Brief Summary

This study is an open, multicenter, prospective phase I dose escalation clinical trial followed by an expansion cohort. The aim of this study is to asses the Recommended Phase 2 Dose (R2PD) and the safety profile, among other efficacy, in FGFR1/2/3 positive, hormone receptor-positive breast cancer (HRPBC) patients with metastatic disease after progression to the combination of an aromatase inhibitor plus palbociclib, abemaciclib or ribociclib, according RECIST 1.1 criteria.

Conditions

Breast Cancer Metastatic; Hormone Receptor Positive Malignant Neoplasm of Breast

Outcome Measures

Primary Outcomes (2)

• Recommended Phase 2 Dose

  Highest dose at which \<1 out of 6 patients experience a DLT.

  2 months

• Incidence of Treatment-Emergent Adverse Event

  Percentage of patients with each adverse event.

  2 years

Secondary Outcomes (4)

• Progression free survival

  2 years

• Pharmacokinetic interactions of fulvestrant and palbociclib over rogaratinib metabolism.

  2 years

• Pharmacodynamic markers levels of FGFR1 Blockade

  2 years

• Response rate

  1 year

Study Arms (1)

Rogaratinib + palbociclib + fulvestrant

EXPERIMENTAL

Drug: Combination, Rogaratinib + palbociclib + fulvestrant

Interventions

Combination, Rogaratinib + palbociclib + fulvestrant DRUG

Patients will receive rogaratinib, palbociclib and fulvestrant in cycles of 28 days. Escalation Dose will follow a classic 3+3 schedule.The planned dose-levels are as follows: * Level 1: Rogaratinib 400 mg PO BID + standard fulvestrant 500 mg every 2nd weeks until the start of the 2nd cycle, becoming every 4 weeks + palbociclib 100 mg PO per day until day 22 followed by a 7-day rest, escalable to 125 mg per day in cycle 2 (N = 3 patients). * Level 2: Rogaratinib 600 mg PO BID + fulvestrant 500 mg IM every 2nd weeks until the start of the 2nd cycle, becoming every 4 weeks + palbociclib 100 mg PO per day until day 22 followed by a 7-day rest, escalable to 125 mg per day in cycle 2 (N = 6 patients). Treatment will continue until disease progression.

Rogaratinib + palbociclib + fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: In this case gender is important because it is a specific cancer in women.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women ≥18 years-old.
• Diagnostic of metastatic or locally advanced non-resectable breast cancer.
• Ability to understand and signing of the PIS/ICF for FGFR testing. FGFR testing will be performed centrally at CNIO (RNAscope and FISH).
• Ability to understand and signing the written PIS/ICF for study treatment eligibility.
• Availability of fresh tumor biopsy specimen for FGFR1/3 mRNA expression and FISH testing.
• Hormone-receptor positivity defined by at least 5% positivity of ER and/or PR (no central laboratory testing is required).
• Positivity of FGFR1/2/3 by RNA-scope and/or FISH.
• Patients must have undergone a previous hormonal treatment line for metastatic disease, with anastrozole, letrozole or exemestane, plus a cell cycle inhibitor (palbociclib, ribociclib or abemaciclib).
• Recovery of toxicities from previous regimens to equal or below tolerable grade II.
• HER2-negativity (Herceptest 0+, 1+ or 2+ with negative FISH/CISH/SISH).
• ECOG performance status of 0/1.
• Life expectancy of \>24 weeks.
• Adequate bone marrow, liver and renal function as assessed by laboratory requirements:
• Absolute neutrophil count (ANC) ≥ 1,500/mm3
• Hemoglobin ≥ 10 g/dL (without transfusion or erythropoietin .

You may not qualify if:

• Involvement in the planning and/or conduct the study.
• Previous enrollment in the present study.
• Previous or concurrent cancer except:
• Cervical carcinoma in situ.
• Treated basal-cell carcinoma or squamous cell skin cancer.
• Any other cancer curatively treated \> 3 years before the first study drug administration.
• Receipt the last dose of anticancer therapy at least 21 days prior to the first dose of study drug.
• Acute toxic effects of previous anticancer chemotherapy or immunotherapy have to be normalized completely
• Anti-cancer therapy is defined as any agent or combination of agents with clinically proven anti-tumor activity
• Previous treatment with anti-FGFR directed therapies.
• Irradiation of single bony lesions with risk of fracture. Zoledronic acid or denosumab started prior to trial registration is allowed.
• Symptomatic metastatic brain or meningeal tumors.
• History or current condition of an uncontrolled cardiovascular disease including any of the following conditions:
• Congestive heart failure, unstable angina (symptoms of angina at rest) or
• New-onset angina

Sponsors & Collaborators

• Fundacion CRIS de Investigación para Vencer el Cáncer: lead
• Bayer: collaborator
• Pfizer: collaborator
• Apices Soluciones S.L.: collaborator

Study Sites (8)

Institut Català d'oncologia - Hospital Duran I Reynals

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Universitario de Fuenlabrada

Fuenlabrada, Madrid, 28942, Spain

Location

Hospital Quirónsalud Madrid

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Hospital Universitari Arnau de Vilanova de Lleida

Lleida, 25198, Spain

Location

Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Clinico San Carlos

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, Spain

Location

MeSH Terms

Interventions

Rogaratinib; palbociclib; Fulvestrant

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Miguel Ángel Quintela-Fandino

  Centro Nacional de Investigaciones Oncológicas

  PRINCIPAL INVESTIGATOR

• Luis Manso, MD

  Hospital Universitario 12 de Octubre

  PRINCIPAL INVESTIGATOR

• Ramón Colomer i Bosch

  Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open label, prospective, multicenter, single-arm, phase I dose-escalation study.

Study Record Dates

• First Submitted: July 20, 2020
• First Posted: July 23, 2020
• Study Start: November 25, 2020
• Primary Completion: April 4, 2023
• Study Completion: April 4, 2023
• Last Updated: December 28, 2023

Record last verified: 2023-12

Locations

ES (8)