Use of Regorafenib in Recurrent Epithelial Ovarian Cancer

NCT02736305 | Completed Phase 2 DMC

• 1 other identifier: NCC OV-01
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

Regorafenib is an oral multikinase inhibitor that blocks the activity of kinases involved in angiogenesis (VEGFR 1,2,3 and TEK), oncogenesis (KIT, Ret Proto-Oncogene (RET), Raf-1 Proto-Oncogene, Serine/Threonine Kinase (RAF1) and BRAF) and tumour growth (PDGFR and FGFR). Epithelial ovarian cancer (EOC) cell lines frequently express high levels of vascular endothelial growth factor (VEGF) and in vivo preclinical studies evaluating Regorafenib have shown promising activity in ovarian cancer. In the clinic, anti-angiogenesis therapy with bevacizumab (a monoclonal antibody to VEGF) has already emerged as an important cornerstone in the management of ovarian cancer both as part of frontline adjuvant treatment and as second-line therapy for platinum-sensitive recurrent disease. Whilst Regorafenib has been FDA approved for the treatment of patients with metastatic colorectal cancer who have failed prior bevacizumab, it's role in the management of ovarian cancer remains to be defined.

Conditions

Ovarian Neoplasms

Keywords

ovarian; regorafenib; platinum resistant; clear cell; endometrioid

Outcome Measures

Primary Outcomes (1)

• Investigator assessed progression free survival (PFS)

  30 days after the last dose of regorafenib

Secondary Outcomes (3)

• Overall survival (OS)

  30 days after the last dose of regorafenib

• Overall tumour response rate (ORR) as per Gynecological Cancer Intergroup (GCIG) and RECIST v1.1 criteria

  30 days after the last dose of regorafenib

• Treatment Emergent Adverse Events

  30 days after the last dose of regorafenib

Other Outcomes (3)

• Health Related Quality of Life (HRQoL)

  30 days after the last dose of regorafenib

• Maximum Plasma Concentration [Cmax]

  30 days after the last dose of regorafenib

• Area Under the Curve (AUC)

  30 days after the last dose of regorafenib

Study Arms (1)

Regorafenib

EXPERIMENTAL

Patients will receive Regorafenib 120mg once daily, with consideration for dose escalation to 160mg if there are no toxicities

Drug: Regorafenib

Interventions

Regorafenib DRUG

Once a day for 21 days in a 28 days cycle

Also known as: Stivarga

Regorafenib

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent obtained before any study specific procedures. Subjects must be able to understand and willing to sign a written informed consent.
• Patients with histologically and/or cytologically confirmed epithelial ovarian carcinoma (serous, clear cell, endometrioid, mucinous, mixed, carcinosarcoma and others), fallopian tube and primary peritoneal carcinoma.
• Progressive disease following 2 or more prior cytotoxic chemotherapy. Patients may have received prior treatment with bevacizumab.
• Age ≥ 21 years old
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Life expectancy greater than 3 months
• Measurable disease by RECIST 1.1 OR non measurable but evaluable disease such as ascites and pleural effusions attributable to disease or radiologic abnormalities that did not meet RECIST criteria AND a pre-treatment serum Ca-125 level greater than or equal to 2 times the upper limit of normal on 2 occasions at least 1 week apart OR pre treatment Ca-125 level greater or equal to 2 times the upper limit of normal on 2 occasions at least 1 week apart and non evaluable, non measurable disease.
• Adequate liver function as assess by: total bilirubin ≤ 1.5 x upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN or ≤ 5.0 x ULN if liver metastases are present.
• Adequate renal function as assessed by serum creatinine ≤ 1.5 x ULN and glomerular filtration rate (GFR) ≥ 30 ml/min according to Cockcroft-Gault formula.
• Systolic blood pressure ≤ 160 mmHg.
• Women of childbearing potential and men must agree to use adequate contraception since signing of the informed consent form until at least 3 months after the last study drug administration. The investigator or a designated associate is requested to advise the subject on how to achieve adequate birth control. Adequate contraception is defined in the study as any medically recommended method (or combination of methods) as per standard of care.
• International normalized ratio (INR) ≤ 1.5 x ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless receiving treatment with therapeutic anticoagulation. Patients being treated with anticoagulant e.g. heparin will be allowed to participate provided no prior evidence of an underlying abnormality in these parameters exists.

You may not qualify if:

• Patients who are receiving any other investigational agents.
• Previous assignment to treatment during this study. Subjects permanently withdrawn from study treatment participation will not be allowed to re-enter the study.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition used in the study.
• Prior treatment with regorafenib.
• Previous or concurrent cancer that is distinct in primary site of histology from EOC within the last 5 years EXCEPT for curatively treated cervical cancer in situ, non melanoma skin cancer and superficial bladder tumours \[Ta (non invasive tumour), Tis (carcinoma in situ) and T1 (tumour invades lamina propria)\].
• Patients with known brain metastases.
• Uncontrolled inter-current illness including, but not limited to, on going or active infection (\> Grade 2 NCI CTCAE v 4.00), symptomatic congestive heart failure (≥ New York Heart Association (NYHA) class 2), unstable angina pectoris, new onset angina (begun within the last 3 months), myocardial infarction less than 6 months before, cardiac arrhythmia requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted), pre existing poorly controlled hypertension (systolic blood pressure \> 160mmHg or diastolic pressure \> 90 mmHg despite optimal medical management), history of abdominal fistula, history of gastrointestinal perforation and signs or symptoms of bowel obstruction.
• Subjects with phaeochromocytoma.
• Other concurrent severe and/or uncontrolled concomitant medical conditions that could cause unacceptable safety risk or compromise compliance with the protocol.
• Patients unable to swallow orally administered medication and patients with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of either study drug (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome).
• Patients who have undergone major surgery, open biopsy of significant traumatic injury ≤ 28 days prior to starting study drug.
• Patient with bowel resection within the past 1 year.
• Patients with a past history of bowel perforation and abdominal fistula; patients with a recent history of bowel resection (within the past 12 months) and/or patients with symptoms of radiological evidence of active bowel obstruction.
• Extended field radiotherapy within 4 weeks or limited field radiotherapy within 2 weeks prior to randomization. Patients must have recovered from all therapy related toxicities. The site of previous radiotherapy should have evidence of progressive disease if this is the only site of disease.
• Patients with venous thromboembolism disease or pulmonary embolism within 6 months before start of study medication (except for adequately treated catheter-related venous thrombosis occurring more than one month before the start of study medication).

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead

Study Sites (1)

National Cancer Centre Singapore

Singapore, 169610, Singapore

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

regorafenib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Wen Yee Chay, MBBS

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 13, 2015
• First Posted: April 13, 2016
• Study Start: February 3, 2016
• Primary Completion: November 18, 2019
• Study Completion: November 18, 2019
• Last Updated: June 13, 2022

Record last verified: 2022-06

Locations

SG (1)