What side effects are associated with this type of intervention?

Common treatments for ovarian cancer, including chemotherapy, targeted therapies, and hormone therapies, have various side effects. Chemotherapy agents like cyclophosphamide can cause alopecia, nausea, vomiting, and myelosuppression. Targeted therapies, such as regorafenib, may lead to hypertension, hand-foot skin reactions, diarrhea, and fatigue. Hormone therapies like fulvestrant can cause hot flashes, fatigue, and injection site reactions. These treatments aim to target cancer cells or specific pathways but can also affect normal cells, leading to these side effects.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of ovarian cancer, particularly those targeting specific cancer pathways. PARP inhibitors such as olaparib, niraparib, and rucaparib have been approved for maintenance therapy in patients with recurrent ovarian cancer, especially those with BRCA mutations. Additionally, bevacizumab, an antiangiogenic agent, has been approved for use in combination with chemotherapy for advanced ovarian cancer. These treatments focus on disrupting cancer cell repair mechanisms and inhibiting blood vessel growth to the tumor, respectively.

What other types of research exist?

Promising novel alternatives for ovarian cancer patients in 2024 include: 1) PI3K/PTEN/AKT/mTOR pathway inhibitors such as temsirolimus and everolimus, which have shown some efficacy in clinical trials. 2) Angiogenesis inhibitors like bevacizumab, which is used in combination with chemotherapy and as maintenance therapy. 3) PARP inhibitors, particularly for patients with BRCA mutations, which have shown effectiveness in maintenance therapy. These alternatives target specific pathways involved in ovarian cancer progression and have demonstrated potential in clinical studies.

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Hormone Therapy

Regorafenib + Fulvestrant for Ovarian Cancer

Phase 2

Recruiting

Led By Kristine Zanotti, MD

Research Sponsored by Sarah K. Lynam MD

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Platelet count >100000 /mm3, hemoglobin (Hb) >9 g/dL, absolute neutrophil count (ANC)> 1500/mm3. Blood transfusion to meet the inclusion criteria will not be allowed.

Prior anti-angiogenesis therapy is not allowed except for bevacizumab.

Must not have

Presence of a non-healing wound, non-healing ulcer, or bone fracture.

Requirement for intravenous alimentation;

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years from start of study

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include high blood pressure, fatigue, hand-foot skin reactions (redness and pain on palms or soles), diarrhea, decreased appetite, infection risks due to lowered immune function, voice changes (hoarseness), increased liver enzymes indicating liver injury.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My blood counts meet the required levels without transfusions.

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I have not received any anti-angiogenesis therapy except for bevacizumab.

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I have a tumor that can be measured and there is tissue from it saved for testing.

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I can swallow and keep down pills.

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I can take care of myself and am up and about more than half of my waking hours.

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I am 18 years old or older.

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My ovarian cancer has come back and is low-grade.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I need to be fed through my veins.

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I have had an organ transplant or am allergic to the study drugs.

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I am on medication for irregular heartbeats not including beta blockers or digoxin.

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I cannot take medicine by mouth.

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I have previously used regorafenib or similar medications.

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I am not using any herbal remedies like St. John's wort.

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I do not have severe breathing problems due to fluid in my chest or abdomen.

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I do not have severe dehydration.

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I am taking low doses of heparin to prevent blood clots.

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I do not have a current infection or it is mild.

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I have not had severe bleeding in the last 4 weeks.

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I have been diagnosed with phaeochromocytoma.

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I have brain or meningeal tumors that are causing symptoms.

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My urine tests show very high protein levels.

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My high blood pressure is not controlled even with medication.

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My cancer is not low-grade serous type.

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I am on medication for seizures.

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I have a history of bleeding disorders or blood clotting issues.

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I am at risk for or have an active bowel perforation or fistula.

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I cannot take pills by mouth due to a blockage in my intestines.

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I am not receiving any cancer treatments other than regorafenib with fulvestrant.

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I am not pregnant or breastfeeding.

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I have been diagnosed with sarcoma, carcinosarcoma, or high grade carcinoma.

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I do not have any serious heart conditions.

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I require dialysis for kidney failure.

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My heart condition does not severely limit my daily activities.

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I currently have symptoms of interstitial lung disease.

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I have a condition that affects how my body absorbs nutrients.

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I have not had major surgery or a serious injury in the last 28 days.

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I take 100 mg or less of aspirin daily.

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I have active heart disease related to my arteries.

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I have been treated for an active stomach ulcer in the last 6 months.

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I have had serious GI bleeding not caused by cancer in the last 3 months without proof of it being resolved.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years from start of study

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years from start of study

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3 years from start of study for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Complete Response Rate of the Drug Regimen

Partial Response Rate of the Drug Regimen

Secondary study objectives

Assess Toxicity of this Combined Regime

Clinical Benefit Rate

Overall Survival in Months

+1 more

Other study objectives

Identify genomic related markers

Side effects data

From 2019 Phase 1 & 2 trial • 495 Patients • NCT02024607

82%

Diarrhoea

76%

Nausea

71%

Fatigue

57%

Vomiting

53%

Abdominal pain

30%

Neuropathy peripheral

27%

Dyspnoea

25%

Anaemia

23%

Neutrophil count decreased

23%

Constipation

22%

Weight decreased

21%

Hypokalaemia

20%

Oedema peripheral

18%

Dehydration

17%

Cough

17%

Neutropenia

17%

Pyrexia

17%

Peripheral sensory neuropathy

16%

Thrombocytopenia

15%

Platelet count decreased

15%

Back pain

13%

Mucosal inflammation

13%

Temperature intolerance

13%

Dysgeusia

13%

Chromaturia

12%

White blood cell count decreased

12%

Urinary tract infection

11%

Dizziness

11%

Depression

10%

Hyponatraemia

10%

Stomatitis

10%

Ascites

10%

Dysphagia

10%

Anxiety

Headache

Abdominal distension

Insomnia

Arthralgia

Asthenia

Pain in extremity

Alopecia

Urine ketone body present

Blood alkaline phosphatase increased

Pulmonary embolism

Lymphopenia

Leukopenia

Blood bilirubin increased

Dyspepsia

Sepsis

Palmar-plantar erythrodysaesthesia syndrome

Hypertension

Urine leukocyte esterase positive

Abdominal pain upper

Gastrooesophageal reflux disease

Proteinuria

Rash

Flatulence

Chills

Dry mouth

Myalgia

Epistaxis

Muscle spasms

Pneumonia

pelvic fracture

Haematemesis

Disease progression

Pleural effusion

Confusional state

Mental status changes

malignant neoplasm progression

Large intestine perforation

Oesophagitis

Lung abscess

embolism

pancreatic carcinoma

fall

Death

Haemorrhage intranial

Atrial fibrillation

Colitis

Enterocutaneous fistula

Gastrointestinal haemorrhage

Upper gastrointestinal haemorrhage

Chest pain

somnolence

syncope

Febrile neutropenia

Acute kidney injury

Acute respiratory failure

Hypoxia

Pneumonia aspiration

Clostridium difficile colitis

Influenza

Perirectal abscess

Salmonella sepsis

Septic shock

hip fracture

deep vein thrombosis

haematoma

pelvic venous thrombosis

Cholangitis

Ischaemic cerebral infarction

Hyperglycaemia

subdural haematoma

100%

80%

60%

40%

20%

Study treatment Arm

Napabucasin Plus FOLFOX6

Napabucasin Plus FOLFOX6 Plus Bevacizumab

Napabucasin Plus FOLFIRI Plus Bevacizumab

Napabucasin Plus Regorafenib

Napabucasin Plus FOLFIRI

Napabucasin Plus Irinotecan

Napabucasin Plus CAPOX

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Oral Regorafenib combined with intra-muscular injection of FulvestrantExperimental Treatment2 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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Regorafenib

2014

Completed Phase 2

~1600

Fulvestrant

2011

Completed Phase 3

~3510

0 / 41Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for ovarian cancer include chemotherapy, targeted therapy, and hormone therapy. Chemotherapy agents like paclitaxel and carboplatin disrupt cell division, leading to cancer cell death. Targeted therapies, such as PARP inhibitors, exploit genetic vulnerabilities in cancer cells to prevent DNA repair and induce cell death. Hormone therapies, like fulvestrant, block hormone receptors or decrease hormone production, which is crucial for hormone-sensitive cancers like low-grade serous ovarian cancer. Understanding these mechanisms helps tailor treatments to specific cancer types, potentially improving outcomes and minimizing side effects.