Regorafenib in Relapsed Glioblastoma

NCT02926222 | Completed Phase 2

• 2 other identifiers: IOV-GB-1-2014 REGOMA2014-003722-41
• Study Type: interventional
• Target: 119
• Locations: 1 country
• Sites: 10

Brief Summary

This study aims to evaluate the role of Regorafenib in prolonging the overall survival of glioblastoma multiforme patients who progressed after surgery and Stupp regimen with or without bevacizumab.

Conditions

Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (1)

• Overall survival

  From the date of randomization to 18 months or to the date of death from any cause

Secondary Outcomes (4)

• Progression free survival

  From the date of randomization to 18 months or to the date of disease progression or to the date of death, whichever occurs first

• Objective response rate

  Approximately 36 months

• Disease control rate

  Approximately 36 months

• Toxicity (Graded according to the NCI-Common Terminology Criteria for Adverse Events)

  Approximately every 4 weeks through the treatment period up to 30 days after the end of treatment

Other Outcomes (1)

• Quality of life EORTC

  From the date of randomization, approximately every 3 months until the date of first documented progression or date of death from any cause, or study withdrawal, whichever came first, assessed up to 30 months.

Study Arms (2)

ARM A - Regorafenib

EXPERIMENTAL

Patients receive REGORAFENIB 40 mg tablets once daily (160 mg/die), 3 weeks on, 1 week off, until disease progression or unacceptable toxicity.

Drug: Regorafenib

ARM B - Lomustine

ACTIVE COMPARATOR

Patients receive LOMUSTINE 110 mg/m2 orally on day 1, every 6 weeks (q6w), until disease progression or unacceptable toxicity.

Drug: Lomustine

Interventions

Regorafenib DRUG

Regorafenib is formulated as tablets of 40mg for oral administration.

Also known as: Stivarga

ARM A - Regorafenib

Lomustine DRUG

Lomustine is formulated as tablets of 40mg for oral administration.

Also known as: Ceenu

ARM B - Lomustine

Eligibility Criteria

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

You may qualify if:

• Male or female ≥ 18 years of age
• Histologically confirmed de novo glioblastoma multiforme (grade IV)
• First recurrence after adjuvant treatment (surgery followed by radiotherapy and temozolomide chemotherapy with or without bevacizumab) in patients who have not received further therapeutic interventions
• For patients not undergoing a second surgery at the time of relapse, recurrent disease must include at least one bi-dimensionally measurable contrast-enhancing lesion with clearly defined margins by MRI scan, with minimal diameters of 10 mm, visible on 2 or more axial slices 5 mm apart, based on an MRI scan done within 2 weeks prior to randomization
• Documented progression of disease as defined by RANO criteria at least 12 weeks after completion of radiotherapy, unless the recurrence is outside the radiation field or has been histologically documented
• Have adequate bone marrow function, liver function, and renal function, as measured by the following laboratory assessments conducted within 7 days prior to the initiation of study treatment:
• Hemoglobin \>9.0 g/dl
• Absolute neutrophil count (ANC) \>1500/mm3 without transfusions or granulocyte colony stimulating factor and other hematopoietic growth factors
• Platelet count ≥100,000/μl
• White blood cell count (WBC) \>3.0 x 109/L
• Total bilirubin \<1.5 times the upper limit of normal
• ALT and AST \<3 x upper limit of normal (\<5 x upper limit of normal for patients with liver involvement of their cancer and/or have bone metastasis)
• Serum creatinine \<1.5 x upper limit of normal
• Alkaline phosphatase \<2.5 x ULN (\<5 x upper limit of normal for patients with liver involvement of their cancer and/or have bone metastasis)
• PT-INR/PTT \<1.5 x upper limit of normal (Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists per medical history)

You may not qualify if:

• Are taking strong cytochrome P (CYP) CYP3A4 inhibitors (eg, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole) or strong CYP3A4 inducers (eg, carbamazepine, phenobarbital, phenytoin, rifampin, St. John's Wort)
• Radiotherapy within 12 weeks prior to the diagnosis of progression, if the lesion is in the radiation field,
• Have had systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and/or hormonal therapy within 4 weeks prior to initiation of study treatment
• Positioning of carmustin wafers during first or second surgery
• Other active or inactive malignancy (except for carcinoma in situ of the cervix, of the prostate or basal cell carcinoma). Malignancy will be considered inactive if patients are in complete remission for at least 3 years prior to study entry
• Have had prior treatment with regorafenib or any other VEGFR-targeting kinase inhibitor
• Have had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of study treatment
• Are pregnant
• Are breastfeeding
• Are unable to swallow oral tablets (crushing of study treatment tablets is not allowed)
• Have congestive heart failure classified as New York Heart Association Class 2 or higher
• Have had unstable angina (angina symptoms at rest) or new-onset angina ≤ 3 months prior to screening.
• Have had a myocardial infarction \< 6 months prior to initiation of study treatment
• Have cardiac arrhythmias requiring anti-arrhythmic therapy, with the exception of beta blockers or digoxin
• Have uncontrolled hypertension (systolic blood pressure \[SBP\] \> 140 mmHg or diastolic blood pressure \[DBP\] \> 90 mmHg) despite optimal medical management

Sponsors & Collaborators

• Istituto Oncologico Veneto IRCCS: lead
• BAYER S.p.A. - Italia: collaborator

Study Sites (10)

IRCCS "Saverio de Bellis

Castellana Grotte, BA, 70013, Italy

Location

Ospedale di Bellaria

Bologna, BO, Italy

Location

Azienda Ospedaliera "G.Rummo"

Benevento, BR, Italy

Location

istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori

Cesena, FC, 47014, Italy

Location

Istituto Neurologico C. Besta IRCCS

Milan, MI, 20133, Italy

Location

Istituto Oncologico Veneto IRCCS, Oncologia Medica 1

Padua, PD, 35128, Italy

Location

Ospedale Santa Chiara

Pisa, PI, 56126, Italy

Location

Azienda Ospedaliero Universitaria S. Maria della Misericordia

Udine, UD, 33100, Italy

Location

Istituto Nazionale Tumori Regina Elena

Roma, 00144, Italy

Location

Azienda Ospedaliera Universitaria Città della Salute e della Scienza

Torino, 10126, Italy

Location

Related Publications (2)

• Lombardi G, Del Bianco P, Brandes AA, Eoli M, Ruda R, Ibrahim T, Lolli I, Rizzato S, Daniele B, Pace A, Pasqualetti F, Caccesse M, Bergo E, Magni G, De Salvo GL, Zagonel V. Patient-reported outcomes in a phase II randomised study of regorafenib compared with lomustine in patients with relapsed glioblastoma (the REGOMA trial). Eur J Cancer. 2021 Sep;155:179-190. doi: 10.1016/j.ejca.2021.06.055. Epub 2021 Aug 10.

  PMID: 34388515 DERIVED

• Lombardi G, De Salvo GL, Brandes AA, Eoli M, Ruda R, Faedi M, Lolli I, Pace A, Daniele B, Pasqualetti F, Rizzato S, Bellu L, Pambuku A, Farina M, Magni G, Indraccolo S, Gardiman MP, Soffietti R, Zagonel V. Regorafenib compared with lomustine in patients with relapsed glioblastoma (REGOMA): a multicentre, open-label, randomised, controlled, phase 2 trial. Lancet Oncol. 2019 Jan;20(1):110-119. doi: 10.1016/S1470-2045(18)30675-2. Epub 2018 Dec 3.

  PMID: 30522967 DERIVED

MeSH Terms

Conditions

Glioblastoma

Interventions

regorafenib; Lomustine

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds

Study Officials

• Vittorina Zagonel, MD

  Istituto Oncologico Veneto IRCCS

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 22, 2016
• First Posted: October 6, 2016
• Study Start: November 1, 2015
• Primary Completion: July 1, 2017
• Study Completion: June 1, 2021
• Last Updated: September 9, 2022

Record last verified: 2022-09

Locations

IT (10)