What side effects are associated with this type of intervention?

Common treatments for liver cancer, particularly receptor tyrosine kinase inhibitors like cabozantinib, often have a range of side effects. These can include fatigue, hepatotoxicity (liver damage), gastrointestinal issues (nausea, diarrhea, vomiting, constipation), and elevated transaminases. Other notable side effects may include vision disorders, edema, and more serious toxicities such as interstitial lung disease or pneumonitis, and QT-interval prolongation. Regular clinical monitoring is essential to manage these potential adverse effects.

What prior FDA approvals exist?

The FDA has approved several receptor tyrosine kinase inhibitors for the treatment of liver cancer, particularly hepatocellular carcinoma (HCC). Sorafenib (Nexavar) was one of the first approved, demonstrating efficacy in advanced HCC by inhibiting RAF kinase and vascular endothelial growth factor receptors (VEGFR). Lenvatinib (Lenvima) has also been approved as a first-line treatment, showing noninferiority to sorafenib. Regorafenib (Stivarga) is another approved option for patients who have progressed on sorafenib. These drugs, like cabozantinib, target multiple pathways involved in tumor growth and angiogenesis, providing systemic treatment options for advanced liver cancer.

What other types of research exist?

Promising alternatives to Cabozantinib for liver cancer treatment include Regorafenib, which is another receptor tyrosine kinase inhibitor used as a second-line treatment for advanced hepatocellular carcinoma. Additionally, Atezolizumab combined with Bevacizumab has shown significant efficacy in treating unresectable hepatocellular carcinoma. These alternatives have been evaluated in clinical trials and have demonstrated potential benefits for liver cancer patients.

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Tyrosine Kinase Inhibitor

Cabozantinib for Liver Cancer

Q: What is the mechanism of action of this treatment?

Common treatments for liver cancer, such as cabozantinib, work by inhibiting receptor tyrosine kinases, which are proteins involved in the signaling pathways that promote tumor growth and angiogenesis (formation of new blood vessels). Cabozantinib specifically targets pathways like c-MET/ERK/p21/PKM2 and VEGFR2, which are essential for cancer cell proliferation and blood supply to tumors. This inhibition can slow down or stop the progression of the cancer. Understanding these mechanisms is crucial for liver cancer patients as it highlights how these treatments can effectively control tumor growth and potentially improve survival outcomes.

Phase 2

Recruiting

Led By Jennifer Knox, M.D.

Research Sponsored by University Health Network, Toronto

Eligibility Criteria Checklist

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

Must have

Previously underwent a liver transplant as a curative treatment for hepatocellular carcinoma (HCC)

Not amenable to curative surgery or local treatment for recurrent disease

Must not have

Receiving any other investigational agents

Had systemic therapy or radiotherapy <3 weeks

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 3 years

Awards & highlights

Approved for 5 Other Conditions

No Placebo-Only Group

All Individual Drugs Already Approved

Summary

This trial tests cabozantinib in patients with liver cancer who had a liver transplant but whose cancer has returned. Cabozantinib works by blocking proteins that help cancer cells grow. The goal is to see if this drug can control the disease in these patients.

Who is the study for?

Adults who've had a liver transplant to treat hepatocellular carcinoma (liver cancer) but now have recurrence. They should not have tried cabozantinib before, may have had one prior therapy for advanced cancer, and must be able to swallow pills. Excluded are those with recent treatments, other serious health issues like infections or heart problems, pregnant women, or anyone with conditions that might interfere with the trial.

What is being tested?

The study is testing cabozantinib's effectiveness in controlling recurrent liver cancer after a transplant. It targets proteins involved in tumor growth. Participants will take this drug until it stops working for them or side effects become too severe.

What are the potential side effects?

Cabozantinib can cause hand-foot skin reactions, diarrhea, weight loss due to decreased appetite, fatigue, high blood pressure and mouth sores. More serious side effects could include bleeding complications and holes in the stomach or intestines.

Eligibility Criteria

Inclusion Criteria

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

Select...

You had a liver transplant in the past to treat liver cancer.

Select...

Your cancer cannot be treated with surgery or other local treatments that can cure it.

Exclusion Criteria

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

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 3 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Disease control rate

Secondary study objectives

Number of Side Effects Reported

Overall survival

Progression-free survival

Side effects data

From 2022 Phase 2 trial • 45 Patients • NCT02101736

95%

HYPOTHYROIDISM

73%

DIARRHEA

55%

WEIGHT LOSS

50%

FATIGUE

41%

ALANINE AMINOTRANSFERASE INCREASED

41%

Neutrophil Count Decreased

41%

ASPARTATE AMINOTRANSFERASE INCREASED

41%

VOMITING

41%

ANOREXIA

41%

NAUSEA

36%

HEADACHE

36%

PALMAR-PLANTAR ERYTHRODYSESTHESIA SYNDROME

36%

PAIN IN EXTREMITY

36%

HYPERTENSION

32%

PROTEINURIA

32%

PAIN

27%

White Blood Cell Count Decreased

27%

ABDOMINAL PAIN

23%

PLATELET COUNT DECREASE

23%

HYPONATREMIA

23%

Decreased Platelet Count

23%

Platelet Count Decreased

23%

Skin Hypopigmentation

23%

Renal & Urinary Disorders - Other, Ketonuria

23%

HAIR COLOR CHANGE

18%

HEMOGLOBIN INCREASED

18%

HYPOKALEMIA

18%

Upper Respiratory Infection

18%

HYPOPHOSPHATEMIA

18%

Alopecia

18%

Hyperkalemia

14%

Rash Acneiform

14%

Pruritis

14%

Rash Maculopapular

14%

HYPOGLYCEMIA

14%

HYPERGLYCEMIA

14%

BILIRUBIN INCREASED

14%

ACNEIFORM RASH

14%

Cough

14%

Blood Bilirubin Increased

14%

DIZZINESS

14%

Skin And Subcutaneous Disorders - Other, Achromotricia

14%

CONSTIPATION

14%

Fever

TUMOR PAIN

Papulopustular Rash

ALKALINE PHOSPHATASE INCREASED

LIPASE INCREASED

Creatinine Increased

Back Pain

ABSOLUTE NEUTROPHIL COUNT DECREASED

Paresthesia

Skin And Subcutaneous Tissue Disorders- Other, Rash Unspecified

ORAL PAIN

LYMPHOCYTE COUNT DECREASED

NASAL CONGESTION

WEIGHT GAIN

HYPOCALCEMIA

DRY SKIN

Muscle Weakness Lower Limb

Neuropathy

Allergic Rhinitis

Hypotension

Hypertension

SERUM AMYLASE INCREASED

Investigations - Other, Eosinophilia

Sore Throat

HEMATURIA

ANXIETY

Hypermagnesemia

Rash Ezcematoid

Gastrointestinal Disorders - Other, Dental Pain

Scalp Pain

DIFFICULTY WALKING, BACK PAIN, BOWEL/BLADDER URGENCY, LEGS GAVE OUT, AND PARESTHESIAS

Psychiatric Disorders - Other, Mood Swings

URINARY URGENCY

Sinus Tachycardia

Periodontal Disease

Peripheral Sensory Neuropathy

Scalp Lesion

Myalgia

Tooth Infection

RASH

Peripheral Motor Neuropathy

Tachycardia

URINARY FREQUENCY

Conjunctivitis

Sinusitis

Syncope

Activated Partial Thromboplastin Time Prolonged

Breast Pain

JOINT RANGE OF MOTION DECREASED

INSOMNIA

Gastrointestinal Disorders - Other, Buccal Cyst

Skin And Subcutaneous Disorders - Other, Dry Skin Patches

Investigations - Other, International Normalized Ration Increased

Musculoskeletal And Connective Tissue Disorders - Other, Extremity Cramps

Joint Range Of Motion Decreased

Behaviour Disturbance

Musculoskeletal And Connective Tissue Disorder - Other, Tendinitis

Skin And Subcutaneous Tissue Disorders- Other, Sore On Lips

Infections And Infestations - Other, Gi Viral Infection

Stomach Pain

TENDONITIS

SKIN INFECTION

HYPOMAGNESEMIA

Muscle Weakness Upper Limb

Skin And Subcutaneous Tissue Disorders - Other, Skin Color Change

Skin And Subcutaneous Tissue Disorders- Other, Blister/Bug Bite On Finger

Surgical & Medical Procedures - Other, Dental Extractions

Skin And Subcutaneous Tissue Disorders- Other, Erythema

Infections And Infestations - Other, Covid-19

Investigations - Other, Increased Mean Corpuscular Volume

Skin And Subcutaneous Tissue Disorders- Other, Transient Erythema

SUBJECT WAS ADMITTED TO THE HOSPITAL ON 10/24/20 WITH GRADE 2 WEIGHT LOSS THAT THE PHYSICIAN FELT NE

Injury, Poisoning And Procedural Complications - Other, Ankle Injury

Injury, Poisoning And Procedural Complications- Other, Scalp Laceration

Skin And Subcutaneous Tissue Disorders- Other, New Freckles/Moles

SINUS BRADYCARDIA

HYPERTHYROIDISM

Creatine Phosphokinase Increased

Skin And Subcutaneous Tissue Disorders - Other: Blue Lips (Not Cyanosis)

Urine Discoloration

SPINAL CORD COMPRESSION

ANEMIA

PARONYCHIA

BRUISING

HYPOALBUMINEMIA

Ear And Labyrinth Disorders - Other, Impacted Cerumen

Ear Pain

Elevated Amylase

Facial Pain

Gastrointestinal Disorders - Other, Stomatitis

Hoarseness

Laryngitis

Leg Pain

Localized Edema

Lung Infection

Metabolism And Nutrition Disorders - Other, Decreased Oral Intake

Metabolism Other - Decreased Vitamin D

Metbolism And Nutrition Disorders - Other, Hyperchloremia

Mucositis Oral

100%

80%

60%

40%

20%

Study treatment Arm

Cohort B

Cohort A

Awards & Highlights

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

No Placebo-Only Group

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

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Trial Design

1Treatment groups

Experimental Treatment

Group I: CabozantinibExperimental Treatment1 Intervention

Cabozantinib, at a dose of 60 mg orally (by mouth), once a day (at bedtime), continuously.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cabozantinib

FDA approved

0 / 23Eligibility 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 liver cancer, such as cabozantinib, work by inhibiting receptor tyrosine kinases, which are proteins involved in the signaling pathways that promote tumor growth and angiogenesis (formation of new blood vessels). Cabozantinib specifically targets pathways like c-MET/ERK/p21/PKM2 and VEGFR2, which are essential for cancer cell proliferation and blood supply to tumors. This inhibition can slow down or stop the progression of the cancer. Understanding these mechanisms is crucial for liver cancer patients as it highlights how these treatments can effectively control tumor growth and potentially improve survival outcomes.

Cabozantinib-based combination therapy for the treatment of hepatocellular carcinoma.Targeting molecular signal transduction pathways in hepatocellular carcinoma and its implications for cancer therapy.M2 macrophages mediate sorafenib resistance by secreting HGF in a feed-forward manner in hepatocellular carcinoma.