Regorafenib + Fulvestrant for Ovarian Cancer

Recruiting at 1 trial location

Overseen By Sarah Lynam, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Sarah K. Lynam MD

Must not be taking: Herbal remedies

Disqualifiers: Hypertension, Cardiac disease, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

31 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well Regorafenib combined with hormone therapy works for patients with recurrent low-grade serous ovarian cancer. Regorafenib helps by stopping cancer cells from growing and forming new blood vessels. The treatment continues until the cancer progresses or side effects become too severe.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but it does allow certain medications like warfarin and heparin with close monitoring. It's best to discuss your specific medications with the trial team.

Is the combination of Regorafenib and Fulvestrant safe for humans?

Regorafenib, also known as Stivarga, has been used in humans for various cancers and is generally considered safe, though it can cause side effects like hand-foot skin reaction, high blood pressure, diarrhea, and fatigue. These side effects are usually manageable with dose adjustments or supportive care. ^{1 2 3 4 5}

What makes the drug Regorafenib + Fulvestrant unique for treating ovarian cancer?

Regorafenib is a unique drug because it is an oral multikinase inhibitor that targets multiple pathways involved in tumor growth, including blood vessel formation and cancer cell proliferation. This combination with Fulvestrant, which is a hormone therapy, may offer a novel approach for ovarian cancer, especially since there are limited standard treatments for this condition. ^{1 2 3 6 7}

What data supports the effectiveness of the drug Regorafenib for ovarian cancer?

Regorafenib has shown benefits in other cancers, like colorectal and liver cancer, by improving survival and slowing disease progression. While specific data for ovarian cancer is limited, its success in other cancers suggests potential effectiveness. ^{1 2 6 8 9}

Who Is on the Research Team?

Sarah Lynam, MD

Principal Investigator

Case Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with recurrent low-grade serous ovarian cancer who've had up to five previous treatments, including MEK inhibitors and aromatase inhibitors. They must have measurable disease, be in a stable health condition (ECOG 0-2), not pregnant or breastfeeding, willing to use contraception, and able to take oral meds. Exclusions include other cancer types or significant health issues like uncontrolled hypertension or recent major surgeries.

Inclusion Criteria

Your bilirubin levels are not too high.

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.

My blood counts meet the required levels without transfusions.

Exclusion Criteria

I have a wound, ulcer, or bone fracture that is not healing.

I need to be fed through my veins.

Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral regorafenib and intramuscular fulvestrant in a 28-day cycle until disease progression or unacceptable toxicities

12 weeks

Weekly visits for the first 3 weeks of each cycle

Maintenance Therapy

For participants with a complete response, maintenance therapy with both drugs will be continued for 12 months

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Fulvestrant
• Regorafenib

Trial Overview The effectiveness of Regorafenib combined with Fulvestrant hormone therapy is being tested on participants with recurrent low-grade serous ovarian cancer. The study aims to see if this combination improves outcomes compared to current standard treatments.

How Is the Trial Designed?

Group I: Oral Regorafenib combined with intra-muscular injection of Fulvestrant Experimental Treatment 2 Interventions

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

Fulvestrant is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in United States as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in Canada as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in Japan as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Who Is Running the Clinical Trial?

Sarah K. Lynam MD

Lead Sponsor

Trials

1

Recruited

30+

Afshin Dowlati, MD

Lead Sponsor

Trials

2

Recruited

50+

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Published Research Related to This Trial

Regorafenib is an oral multi-kinase inhibitor that has shown significant survival benefits in metastatic colorectal cancer and has been FDA approved for this use since 2012.

The drug also improves progression-free survival in patients with metastatic gastrointestinal stromal tumors and advanced hepatocellular carcinoma, leading to its FDA approval for these conditions as well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib. Ettrich, TJ., Seufferlein, T.[2018]

Regorafenib is an FDA-approved oral medication that targets multiple kinases involved in cancer growth and has shown survival benefits in patients with metastatic colorectal cancer after standard treatments have failed.

In addition to colorectal cancer, regorafenib significantly improves progression-free survival in patients with metastatic gastrointestinal stromal tumors (GIST) and is currently being tested in various other cancers, including renal cell carcinoma and hepatocellular carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib. Ettrich, TJ., Seufferlein, T.[2015]

In a study involving patients with metastatic colorectal cancer, prophylactic oral dexamethasone (DEX) showed a trend towards reducing the incidence of grade ≥2 fatigue and malaise compared to placebo, with 19.4% in the DEX group versus 38.9% in the placebo group.

Although the overall incidence of fatigue and malaise was similar between the DEX and placebo groups, patient-reported outcomes indicated a significant reduction in fatigue with DEX, suggesting it may be clinically effective in managing regorafenib-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic Effect of Dexamethasone on Regorafenib-Related Fatigue and/or Malaise: A Randomized, Placebo-Controlled, Double-Blind Clinical Study in Patients with Unresectable Metastatic Colorectal Cancer (KSCC1402/HGCSG1402). Tanioka, H., Miyamoto, Y., Tsuji, A., et al.[2018]

Niraparib, a PARP inhibitor approved in 2020, provides an effective maintenance treatment for ovarian cancer, showing promise regardless of patients' genetic profiles, which is significant given the low survival rates associated with late-stage diagnoses.

The treatment has a low side effect profile and is administered orally, making it a convenient option for patients, while ongoing trials are exploring new combination therapies that could enhance its efficacy further.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib in the maintenance treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer: safety and efficacy. Liu, MC., Sutedja, J., Tewari, KS.[2022]

In a study involving 68 patients with platinum-sensitive ovarian cancer, regorafenib did not show superior efficacy compared to tamoxifen, with similar median progression-free survival of 5.6 months for tamoxifen and 4.6 months for regorafenib.

Regorafenib had a significantly worse safety profile, with 90.9% of patients experiencing grade 3/4 adverse events, compared to 54.3% for tamoxifen, highlighting concerns about its tolerability in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib or Tamoxifen for platinum-sensitive recurrent ovarian cancer with rising CA125 and no evidence of clinical or RECIST progression: A GINECO randomized phase II trial (REGOVAR). Trédan, O., Provansal, M., Abdeddaim, C., et al.[2022]

A new method for measuring regorafenib and its metabolites in human plasma has been developed, showing high sensitivity and specificity, which is crucial for monitoring treatment effectiveness.

The method demonstrated excellent accuracy and precision, making it suitable for analyzing large sample sizes in clinical settings, thus supporting the safe and effective use of regorafenib in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of regorafenib (BAY 73-4506) and its major human metabolites BAY 75-7495 (M-2) and BAY 81-8752 (M-5) in human plasma by stable-isotope dilution liquid chromatography-tandem mass spectrometry. Hafner, FT., Werner, D., Kaiser, M.[2019]

Regorafenib is an effective treatment for advanced gastrointestinal stromal tumors (GISTs) after patients have not responded to imatinib and sunitinib, showing significant improvement in progression-free survival and disease control rates compared to placebo in the phase III GRID trial.

The drug has a manageable safety profile, with common side effects including hand-foot skin reactions, hypertension, diarrhea, and fatigue, which can often be addressed with dose adjustments or supportive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib: A Review of Its Use in Patients with Advanced Gastrointestinal Stromal Tumours. Shirley, M., Keating, GM.[2018]

Regorafenib, a receptor tyrosine kinase inhibitor used for metastatic colorectal cancer and gastrointestinal stromal tumors, has a high incidence of hand-foot skin reaction (HFSR), with an overall occurrence of 60.5% among 1,078 patients studied.

The risk of developing high-grade HFSR is significantly elevated with regorafenib, showing a relative risk of 41.99 compared to controls, and the incidence varies by tumor type, being highest in renal cell carcinoma at 71.4%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of hand-foot skin reaction with the novel multikinase inhibitor regorafenib: a meta-analysis. Belum, VR., Wu, S., Lacouture, ME.[2022]

Regorafenib is an oral multikinase inhibitor approved for treating pretreated metastatic colorectal cancer and gastrointestinal stromal tumors, showing antiangiogenic and antiproliferative effects, based on data from phase III studies.

Currently, regorafenib is being investigated in phase III trials for hepatocellular carcinoma and in several phase II studies for other gastrointestinal tumors, indicating its potential for broader applications in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib as a single-agent in the treatment of patients with gastrointestinal tumors: an overview for pharmacists. Rey, JB., Launay-Vacher, V., Tournigand, C.[2021]

Citations

1. Germany pubmed.ncbi.nlm.nih.gov

Regorafenib. [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

Regorafenib. [2015]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Prophylactic Effect of Dexamethasone on Regorafenib-Related Fatigue and/or Malaise: A Randomized, Placebo-Controlled, Double-Blind Clinical Study in Patients with Unresectable Metastatic Colorectal Cancer (KSCC1402/HGCSG1402). [2018]

4. England pubmed.ncbi.nlm.nih.gov

Niraparib in the maintenance treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer: safety and efficacy. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Regorafenib or Tamoxifen for platinum-sensitive recurrent ovarian cancer with rising CA125 and no evidence of clinical or RECIST progression: A GINECO randomized phase II trial (REGOVAR). [2022]

6. England pubmed.ncbi.nlm.nih.gov

Determination of regorafenib (BAY 73-4506) and its major human metabolites BAY 75-7495 (M-2) and BAY 81-8752 (M-5) in human plasma by stable-isotope dilution liquid chromatography-tandem mass spectrometry. [2019]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Regorafenib: A Review of Its Use in Patients with Advanced Gastrointestinal Stromal Tumours. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Risk of hand-foot skin reaction with the novel multikinase inhibitor regorafenib: a meta-analysis. [2022]

9. France pubmed.ncbi.nlm.nih.gov

Regorafenib as a single-agent in the treatment of patients with gastrointestinal tumors: an overview for pharmacists. [2021]