AzTrials
AzTrials

Breast Cancer MetastaticPhase 1ROGABREASTNCT04483505

Rogaratinib, Palbociclib y Fulvestrant in Patients With Breast Cancer.

A Phase 1 study testing Combination, Rogaratinib + palbociclib + fulvestrant in people with Breast Cancer Metastatic and Hormone Receptor Positive Malignant Neoplasm of Breast, run by Fundacion CRIS de Investigación para Vencer el Cáncer at 8 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Combination, Rogaratinib + palbociclib + fulvestrant
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
8 sitesSpain
Study dates
25 Nov 2020to 4 Apr 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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
Show all 26Show fewer
  • 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 .
  • Platelet count ≥ 100,000/mm3
  • Total bilirubin ≤ 1.5 × the upper limit of normal (ULN).
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN
  • Alkaline phosphatase ≤ 2.5 times ULN
  • Lipase and amylase ≤ 2 × ULN.
  • Serum albumin ≥ 2.5 g/dl.
  • Glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m2
  • INR ≤ 1.5 × ULN and PTT or activated PTT (aPTT) ≤ 1.5 × ULN.
  • Negative serum pregnancy test in women of childbearing potential.
  • Women of reproductive potential must agree to use highly effective contraception when sexually active.
  • Evaluable disease according to RECIST 1.1 criteria.

Who cannot join

  • 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.
Show all 50Show fewer
  • 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
  • Myocardial infarction (MI).
  • Unstable cardiac arrhythmias requiring anti-arrhythmic therapy.
  • Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, must be on a stable medical regimen.
  • Known human immunodeficiency virus (HIV) infection.
  • Active hepatitis B virus or hepatitis C infection requiring treatment.
  • Patients with past HBV infection or resolved HBV infection are eligible if HBV DNA is negative.
  • Patients positive for hepatitis C virus are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Any condition that in the opinion of the investigator would interfere with evaluation of study treatment or interpretation of patient safety or study results, or inability to comply with the study and follow-up procedures.
  • Previous or concomitant participation in another clinical study with investigational medicinal products.
  • Active tuberculosis.
  • Clinically active infections.
  • Treatment with therapeutic oral or i.v. antibiotics.
  • Patients receiving prophylactic antibiotics are eligible.
  • Seizure disorder requiring medication.
  • History of organ allograft.
  • Evidence or history of bleeding diathesis or coagulopathy.
  • Any hemorrhage / bleeding event CTCAE v.5.0 ≥ Grade 3.
  • Serious, non-healing wound, ulcer or bone fracture.
  • Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation.
  • Any malabsorption condition.
  • Current diagnosis of any retinal disorders including retinal detachment, retinal pigment epithelial detachment (RPED), serous retinopathy or retinal vein occlusion.
  • Peripheral sensory neuropathy of CTCAE v.5.0 Grade 2 or higher.
  • Current evidence of endocrine alteration of calcium phosphate homeostasis.
  • Concomitant therapies that are known to increase serum phosphate levels.
  • Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study.
  • Breast-feeding.
  • Use of strong inhibitors of CYP3A4 and strong inducers of CYP3A4.
  • Autologous bone marrow transplant or stem cell rescue.
  • Major surgery, open biopsy or significant traumatic injury.
  • Renal failure requiring peritoneal dialysis or hemodialysis.
  • Systolic/diastolic blood pressure ≤ 100/60 mmHg and concurrent heart rate ≥ 100/min.
  • Inability to swallow oral tablets.
  • Close affiliation with the investigational site; e.g. a close relative of the investigator or a dependent person.
  • Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
  • Arterial or venous thrombotic events or embolic events such as cerebrovascular accident, deep vein thrombosis or pulmonary embolism.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

Spain8 sites

  • Hospital Universitario de Fuenlabrada

    Fuenlabrada, Madrid, 28942

  • Institut Català d'oncologia - Hospital Duran I Reynals

    L'Hospitalet de Llobregat, Barcelona, 08908

  • Hospital Universitari Arnau de Vilanova de Lleida

    Lleida, 25198

  • Hospital Ramon y Cajal

    Madrid, 28034

  • Hospital Clinico San Carlos

    Madrid

  • Hospital Universitario 12 de Octubre

    Madrid

  • Hospital Quirónsalud Madrid

    Pozuelo de Alarcón, Madrid, 28223

  • Hospital Clínico Universitario de Valencia

    Valencia

Other trials in Spain

About this study

Official title: Rogaratinib, Palbociclib and Fulvestrant in Advanced Hormone Receptor Positive, FGFR1/2/3-positive Breast Cancer: Phase I Clinical Trial Plus an Expansion Cohort

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.

Being tested
Combination, Rogaratinib + palbociclib + fulvestrant

What participants receive

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

  • Combination, Rogaratinib + palbociclib + fulvestrantDrug

    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.

Study groups in NCT04483505
Study groupRoleWhat they receive
Rogaratinib + palbociclib + fulvestrantExperimentalNot described
Receives: Drug: Combination, Rogaratinib + palbociclib + fulvestrant

What is being measured

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

  1. Recommended Phase 2 Dose

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

    Measured: 2 months

  2. Incidence of Treatment-Emergent Adverse Event

    Percentage of patients with each adverse event.

    Measured: 2 years

Secondary outcomes (4)

  1. Progression free survival

    Time from the date of first dose of study treatment to the date of progression or death (from any cause).

    Measured: 2 years

  2. Pharmacokinetic interactions of fulvestrant and palbociclib over rogaratinib metabolism.

    Plasmatic levels of fulvestrant, palbociclib and rogaratinib

    Measured: 2 years

  3. Pharmacodynamic markers levels of FGFR1 Blockade

    Plasma levels of phosphate and FGF23.

    Measured: 2 years

  4. Response rate

    Percentage of patients that achieve response according to RECIST 1.1 criteria.

    Measured: 1 year

Timeline

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

  1. First posted23 Jul 2020
  2. Study start25 Nov 2020
  3. Primary completion4 Apr 2023
  4. Study completion4 Apr 2023

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
Other
Allocation
Not applicable
Intervention model
Single group
Model description
Open label, prospective, multicenter, single-arm, phase I dose-escalation study.
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04483505
Sponsor's protocol ID
ROGABREAST
Other IDs
2020-000055-12
Acronym
ROGABREAST
Status last verified
Dec 2023
First submitted
20 Jul 2020
Last updated
28 Dec 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Combination, Rogaratinib + palbociclib + fulvestrant in people with Breast Cancer Metastatic and Hormone Receptor Positive Malignant Neoplasm of Breast, run by Fundacion CRIS de Investigación para Vencer el Cáncer at 8 sites in Spain.

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 26 inclusion and 50 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: finished, as of the sponsor's last update on 28 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Spain. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Recommended Phase 2 Dose (time frame: 2 months). The study lists 2 primary outcomes in all. 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 NCT04483505.

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 28 Dec 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in