Clinical Trials /

Rogaratinib, Palbociclib y Fulvestrant in Patients With Breast Cancer.

NCT04483505

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Rogaratinib, Palbociclib y Fulvestrant in Patients With Breast Cancer.
  • 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

Clinical Trial IDs

  • ORG STUDY ID: ROGABREAST
  • SECONDARY ID: 2020-000055-12
  • NCT ID: NCT04483505

Conditions

  • Breast Cancer Metastatic
  • Hormone Receptor Positive Malignant Neoplasm of Breast

Interventions

DrugSynonymsArms
Combination, Rogaratinib + palbociclib + fulvestrantRogaratinib + palbociclib + fulvestrant

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Rogaratinib + palbociclib + fulvestrantExperimental
  • Combination, Rogaratinib + palbociclib + fulvestrant

Eligibility Criteria

        Inclusion Criteria:

          1. Women ≥18 years-old.

          2. Diagnostic of metastatic or locally advanced non-resectable breast cancer.

          3. Ability to understand and signing of the PIS/ICF for FGFR testing. FGFR testing will
             be performed centrally at CNIO (RNAscope and FISH).

          4. Ability to understand and signing the written PIS/ICF for study treatment eligibility.

          5. Availability of fresh tumor biopsy specimen for FGFR1/3 mRNA expression and FISH
             testing.

          6. Hormone-receptor positivity defined by at least 5% positivity of ER and/or PR (no
             central laboratory testing is required).

          7. Positivity of FGFR1/2/3 by RNA-scope and/or FISH.

          8. 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).

          9. Recovery of toxicities from previous regimens to equal or below tolerable grade II.

         10. HER2-negativity (Herceptest 0+, 1+ or 2+ with negative FISH/CISH/SISH).

         11. ECOG performance status of 0/1.

         12. Life expectancy of >24 weeks.

         13. Adequate bone marrow, liver and renal function as assessed by laboratory requirements:

               1. Absolute neutrophil count (ANC) ≥ 1,500/mm3

               2. Hemoglobin ≥ 10 g/dL (without transfusion or erythropoietin .

               3. Platelet count ≥ 100,000/mm3

               4. Total bilirubin ≤ 1.5 × the upper limit of normal (ULN).

               5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN

               6. Alkaline phosphatase ≤ 2.5 times ULN

               7. Lipase and amylase ≤ 2 × ULN.

               8. Serum albumin ≥ 2.5 g/dl.

               9. Glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m2

         14. INR ≤ 1.5 × ULN and PTT or activated PTT (aPTT) ≤ 1.5 × ULN.

         15. Negative serum pregnancy test in women of childbearing potential.

         16. Women of reproductive potential must agree to use highly effective contraception when
             sexually active.

         17. Evaluable disease according to RECIST 1.1 criteria.

        Exclusion Criteria:

          1. Involvement in the planning and/or conduct the study.

          2. Previous enrollment in the present study.

          3. Previous or concurrent cancer except:

               1. Cervical carcinoma in situ.

               2. Treated basal-cell carcinoma or squamous cell skin cancer.

               3. Any other cancer curatively treated > 3 years before the first study drug
                  administration.

          4. Receipt the last dose of anticancer therapy at least 21 days prior to the first dose
             of study drug.

          5. Acute toxic effects of previous anticancer chemotherapy or immunotherapy have to be
             normalized completely

          6. Anti-cancer therapy is defined as any agent or combination of agents with clinically
             proven anti-tumor activity

          7. Previous treatment with anti-FGFR directed therapies.

          8. Irradiation of single bony lesions with risk of fracture. Zoledronic acid or denosumab
             started prior to trial registration is allowed.

          9. Symptomatic metastatic brain or meningeal tumors.

         10. History or current condition of an uncontrolled cardiovascular disease including any
             of the following conditions:

               1. Congestive heart failure, unstable angina (symptoms of angina at rest) or

               2. New-onset angina

               3. Myocardial infarction (MI).

               4. Unstable cardiac arrhythmias requiring anti-arrhythmic therapy.

               5. Patients with known coronary artery disease, congestive heart failure not meeting
                  the above criteria, must be on a stable medical regimen.

         11. Known human immunodeficiency virus (HIV) infection.

         12. Active hepatitis B virus or hepatitis C infection requiring treatment.

               1. Patients with past HBV infection or resolved HBV infection are eligible if HBV
                  DNA is negative.

               2. Patients positive for hepatitis C virus are eligible only if polymerase chain
                  reaction is negative for HCV RNA.

         13. 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.

         14. Previous or concomitant participation in another clinical study with investigational
             medicinal products.

         15. Active tuberculosis.

         16. Clinically active infections.

         17. Treatment with therapeutic oral or i.v. antibiotics.

         18. Patients receiving prophylactic antibiotics are eligible.

         19. Seizure disorder requiring medication.

         20. History of organ allograft.

         21. Evidence or history of bleeding diathesis or coagulopathy.

         22. Any hemorrhage / bleeding event CTCAE v.5.0 ≥ Grade 3.

         23. Serious, non-healing wound, ulcer or bone fracture.

         24. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in
             the formulation.

         25. Any malabsorption condition.

         26. Current diagnosis of any retinal disorders including retinal detachment, retinal
             pigment epithelial detachment (RPED), serous retinopathy or retinal vein occlusion.

         27. Peripheral sensory neuropathy of CTCAE v.5.0 Grade 2 or higher.

         28. Current evidence of endocrine alteration of calcium phosphate homeostasis.

         29. Concomitant therapies that are known to increase serum phosphate levels.

         30. Any condition that is unstable or could jeopardize the safety of the patient and their
             compliance in the study.

         31. Breast-feeding.

         32. Use of strong inhibitors of CYP3A4 and strong inducers of CYP3A4.

         33. Autologous bone marrow transplant or stem cell rescue.

         34. Major surgery, open biopsy or significant traumatic injury.

         35. Renal failure requiring peritoneal dialysis or hemodialysis.

         36. Systolic/diastolic blood pressure ≤ 100/60 mmHg and concurrent heart rate ≥ 100/min.

         37. Inability to swallow oral tablets.

         38. Close affiliation with the investigational site; e.g. a close relative of the
             investigator or a dependent person.

         39. Substance abuse, medical, psychological or social conditions that may interfere with
             the patient's participation in the study or evaluation of the study results.

         40. Arterial or venous thrombotic events or embolic events such as cerebrovascular
             accident, deep vein thrombosis or pulmonary embolism.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended Phase 2 Dose
Time Frame:2 months
Safety Issue:
Description:Highest dose at which <1 out of 6 patients experience a DLT.

Secondary Outcome Measures

Measure:Progression free survival
Time Frame:2 years
Safety Issue:
Description:Time from the date of first dose of study treatment to the date of progression or death (from any cause).
Measure:Pharmacokinetic interactions of fulvestrant and palbociclib over rogaratinib metabolism.
Time Frame:16 days
Safety Issue:
Description:Plasmatic levels of fulvestrant, palbociclib and rogaratinib
Measure:Pharmacodynamic markers levels of FGFR1 Blockade
Time Frame:16 days
Safety Issue:
Description:Plasma levels of phosphate and FGF23.
Measure:Response rate
Time Frame:1 year
Safety Issue:
Description:Percentage of patients that achieve response according to RECIST 1.1 criteria.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Fundacion CRIS de Investigación para Vencer el Cáncer

Last Updated

July 22, 2020