Regorafenib Combined With Fulvestrant in Recurrent Low-Grade Serous Ovarian Cancer

NCT05113368 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CASE2820
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

To see how effective the study medicine combined with hormone therapy is when given to participants with recurrent low-grade serous ovarian cancer.

Conditions

Ovarian Cancer; Serous Ovarian Cancer

Keywords

Ovarian Cancer; serous ovarian cancer; Fulvestrant; Regorafenib

Outcome Measures

Primary Outcomes (2)

• Complete Response Rate of the Drug Regimen

  To assess the efficacy of this regimen in term of overall objective response rate (complete response rate) at 12 weeks as assessed by the Investigator, per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). The number of participants that reach a complete response (CR) defined as normalization of tumor markers, tumor nodes \<10 mm.

  12 weeks from first cycle of treatment (each cycle is 28 days)

• Partial Response Rate of the Drug Regimen

  To assess the efficacy of this regimen in term of overall objective response rate (partial response rate) at 12 weeks as assessed by the Investigator, per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). The number of participants that reach a partial response (PR)defined as at least a 30% decrease in the sum of diameters of target lesions.

  12 weeks from first cycle of treatment (each cycle is 28 days)

Secondary Outcomes (4)

• Overall Survival in Months

  up to 3 years from start of study

• Progression-free Survival in Months

  up to 3 years from start of study

• Clinical Benefit Rate

  12 weeks

• Assess Toxicity of this Combined Regime

  at 3 months after treatment

Other Outcomes (1)

• Identify genomic related markers

  up to 3 years from start of study

Study Arms (1)

Oral Regorafenib combined with intra-muscular injection of Fulvestrant

EXPERIMENTAL

Oral regorafenib in a ReDOS plan (80 mg week#1, 120 mg week#2, 160 mg week#3 for cycle #1 then adjust final dose for subsequent cycles based on tolerance during cycle #1) \[3 weeks on/1 week off\] combined with intramuscular injection of fulvestrant 500 mg day #1 (day #15 will be planned only in cycle #1) in a 28-day cycle till disease progression or unacceptable toxicities

Drug: Regorafenib; Drug: Fulvestrant

Interventions

Regorafenib DRUG

Oral regorafenib in a ReDOSplan (80 mg week#1, 120 mg week#2, 160 mg week#3 for cycle #1 then adjust final dose for subsequent cycles based on tolerance during cycle #1) \[3 weeks on/1 week off\] combined with intramuscular injection of fulvestrant 500 mg day #1 (day #15 will be planned only in cycle #1) in a 28-day cycle till disease progression or unacceptable toxicities

Oral Regorafenib combined with intra-muscular injection of Fulvestrant

Fulvestrant DRUG

500 mg day #1 (day #15 will be planned only in cycle #1) in a 28-day cycle till disease progression or unacceptable toxicities

Oral Regorafenib combined with intra-muscular injection of Fulvestrant

Eligibility Criteria

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

You may qualify if:

• Subjects must have recurrent low-grade serous ovarian cancer.
• Up to 5 prior lines of therapy are allowed.
• Prior therapy with MEK inhibitors is allowed
• Prior therapy with aromatase inhibitors like letrozole is allowed
• Prior anti-angiogenesis therapy is not allowed except for bevacizumab.
• Subjects must have measurable disease based on RECIST 1.1 with at least one target lesion and with available archival tumor tissue.
• Subjects must have an ECOG performance status of 0-2.
• Age ≥ 18 years.
• Life expectancy of at least 12 weeks (3 months).
• Subjects must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements:
• Total bilirubin ≤ 1.5 x the upper limits of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate amino-transferease (AST) ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer)
• Alkaline phosphastase limit ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer)
• Serum creatinine ≤ 1.5 x the ULN

You may not qualify if:

• Patients with sarcoma, carcinosarcoma or high grade carcinoma
• Any histology type other than low-grade serous histology
• Previous assignment to treatment during this study. Subjects permanently withdrawn from study participation will not be allowed to re-enter study.
• Uncontrolled hypertension (systolic pressure \>150 mm Hg or diastolic pressure \> 90 mm Hg \[NCI-CTCAE v5.0\] on repeated measurement) despite optimal medical management.
• Active or clinically significant cardiac disease including:
• Congestive heart failure - New York Heart Association (NYHA) \> Class II.
• Active coronary artery disease.
• Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin.
• Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before randomization, or myocardial infarction within 6 months before randomization.
• Evidence or history of bleeding diathesis or coagulopathy.
• Any hemorrhage or bleeding event ≥ NCI CTCAE Grade 3 within 4 weeks prior to start of study medication.
• Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism within 6 months of start of study treatment within 6 months of informed consent.
• Patients with any previously untreated or concurrent cancer that is distinct in primary site or histology except cervical cancer in-situ, treated ductal carcinoma in situ of the breast, curatively treated nonmelanoma skin carcinoma, noninvasive aerodigestive neoplasms, or superficial bladder tumor. Subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before registration are allowed. All cancer treatments must be completed at least 3 years prior to registration.
• Patients with phaeochromocytoma.
• Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy. However, patients with chronic HIV with undetectable viral load by PCR, without opportunistic infection, and on a stable regimen of antiretroviral therapy and patients with chronic hepatitis B or C infection with undetectable viral load by PCR and on a stable regimen of antiretroviral therapy would be eligible.

Sponsors & Collaborators

• Sarah K. Lynam MD: lead
• Bayer: collaborator

Study Sites (1)

University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

regorafenib; Fulvestrant

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

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

• Sarah Lynam, MD

  Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah Lynam, MD

CONTACT

1-800-641-2422; Sarah.Lynam@UHhospitals.org

Nancy Fusco, RN

CONTACT

216-844-3954; nancy.fusco@UHhospitals.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, MD

Study Record Dates

• First Submitted: September 26, 2021
• First Posted: November 9, 2021
• Study Start: June 28, 2022
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): February 1, 2027
• Last Updated: August 21, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Beginning 3 months and ending 5 years following article publication
• Access Criteria: Investigators who provide a methodologically sound proposal for use of requested data. Link to be provided at time of article publication.

Locations

US (1)