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PD-L1 Inhibitor

Cabozantinib + Atezolizumab for Liver Cancer (COSMIC-312 Trial)

Phase 3
Waitlist Available
Research Sponsored by Exelixis
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Be older than 18 years old
Timeline
Screening 3 weeks
Treatment Varies
Follow Up up to 20 months after the first subject is randomized.
Awards & highlights

COSMIC-312 Trial Summary

This trial is testing a new combo therapy for liver cancer vs the standard of care. The new therapy includes a drug called cabozantinib.

Who is the study for?
This trial is for adults with advanced liver cancer (HCC) who haven't had systemic anticancer treatments. They should have a specific level of liver function (Child-Pugh Score A), measurable disease, and be in certain stages of the disease (BCLC B or C). Participants must be able to perform daily activities with little assistance (ECOG status 0 or 1). Those with particular types of HCC, previous systemic treatments for advanced HCC, brain metastases not stable post-treatment, recent radiation therapy, or on certain blood thinners can't join.Check my eligibility
What is being tested?
The study compares cabozantinib combined with atezolizumab against sorafenib as standard care in treating advanced liver cancer. It also assesses cabozantinib alone to understand its individual effect. This Phase 3 trial aims to determine which treatment is safer and more effective for patients who are new to systemic anticancer therapies.See study design
What are the potential side effects?
Potential side effects include high blood pressure, tiredness, loss of appetite, gastrointestinal issues like diarrhea and nausea; hand-foot skin reactions; increased risk of bleeding; changes in voice quality; taste alterations; weight loss; elevated liver enzymes indicating possible liver damage.

COSMIC-312 Trial Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~up to 20 months after the first subject is randomized.
This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 20 months after the first subject is randomized. for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.
Primary outcome measures
Duration of Overall Survival (OS) for the experimental arm vs. the control arm
Duration of Progression Free Survival (PFS) for the experimental arm vs. the control arm
Secondary outcome measures
Duration of Progression Free Survival (PFS) for the single-agent arm vs. the control arm

Side effects data

From 2022 Phase 2 trial • 45 Patients • NCT02101736
95%
HYPOTHYROIDISM
73%
DIARRHEA
55%
WEIGHT LOSS
50%
FATIGUE
41%
VOMITING
41%
NAUSEA
41%
ASPARTATE AMINOTRANSFERASE INCREASED
41%
ANOREXIA
41%
ALANINE AMINOTRANSFERASE INCREASED
41%
Neutrophil Count Decreased
36%
HEADACHE
36%
PALMAR-PLANTAR ERYTHRODYSESTHESIA SYNDROME
36%
PAIN IN EXTREMITY
36%
HYPERTENSION
32%
PAIN
32%
PROTEINURIA
27%
ABDOMINAL PAIN
27%
White Blood Cell Count Decreased
23%
Platelet Count Decreased
23%
Skin Hypopigmentation
23%
HAIR COLOR CHANGE
23%
Renal & Urinary Disorders - Other, Ketonuria
23%
PLATELET COUNT DECREASE
23%
HYPONATREMIA
23%
Decreased Platelet Count
18%
HYPOPHOSPHATEMIA
18%
HYPOKALEMIA
18%
Alopecia
18%
Hyperkalemia
18%
Upper Respiratory Infection
18%
HEMOGLOBIN INCREASED
14%
DIZZINESS
14%
BILIRUBIN INCREASED
14%
Pruritis
14%
ACNEIFORM RASH
14%
Fever
14%
Rash Maculopapular
14%
CONSTIPATION
14%
HYPERGLYCEMIA
14%
HYPOGLYCEMIA
14%
Blood Bilirubin Increased
14%
Cough
14%
Rash Acneiform
14%
Skin And Subcutaneous Disorders - Other, Achromotricia
9%
TUMOR PAIN
9%
ORAL PAIN
9%
ALKALINE PHOSPHATASE INCREASED
9%
WEIGHT GAIN
9%
NASAL CONGESTION
9%
Skin And Subcutaneous Tissue Disorders- Other, Rash Unspecified
9%
ABSOLUTE NEUTROPHIL COUNT DECREASED
9%
LIPASE INCREASED
9%
LYMPHOCYTE COUNT DECREASED
9%
HYPOCALCEMIA
9%
DRY SKIN
9%
Back Pain
9%
Creatinine Increased
9%
Papulopustular Rash
9%
Paresthesia
5%
RASH
5%
INSOMNIA
5%
Peripheral Sensory Neuropathy
5%
HYPERTHYROIDISM
5%
SINUS BRADYCARDIA
5%
Hypertension
5%
ANXIETY
5%
Sore Throat
5%
Gastrointestinal Disorders - Other, Buccal Cyst
5%
Myalgia
5%
SPINAL CORD COMPRESSION
5%
SUBJECT WAS ADMITTED TO THE HOSPITAL ON 10/24/20 WITH GRADE 2 WEIGHT LOSS THAT THE PHYSICIAN FELT NE
5%
Gastrointestinal Disorders - Other, Stomatitis
5%
Musculoskeletal And Connective Tissue Disorder - Other, Tendinitis
5%
Hoarseness
5%
Peripheral Motor Neuropathy
5%
Investigations - Other, Eosinophilia
5%
Surgical & Medical Procedures - Other, Dental Extractions
5%
Stomach Pain
5%
TENDONITIS
5%
HEMATURIA
5%
Gastrointestinal Disorders - Other, Dental Pain
5%
DIFFICULTY WALKING, BACK PAIN, BOWEL/BLADDER URGENCY, LEGS GAVE OUT, AND PARESTHESIAS
5%
Musculoskeletal And Connective Tissue Disorders - Other, Extremity Cramps
5%
Facial Pain
5%
HYPOMAGNESEMIA
5%
Allergic Rhinitis
5%
Activated Partial Thromboplastin Time Prolonged
5%
Leg Pain
5%
Muscle Weakness Lower Limb
5%
Muscle Weakness Upper Limb
5%
Psychiatric Disorders - Other, Mood Swings
5%
Scalp Lesion
5%
Scalp Pain
5%
Sinus Tachycardia
5%
Sinusitis
5%
Skin And Subcutaneous Tissue Disorders- Other, Blister/Bug Bite On Finger
5%
Skin And Subcutaneous Tissue Disorders- Other, Erythema
5%
Skin And Subcutaneous Tissue Disorders- Other, Sore On Lips
5%
Skin And Subcutaneous Tissue Disorders- Other, Transient Erythema
5%
Syncope
5%
Tachycardia
5%
Urine Discoloration
5%
JOINT RANGE OF MOTION DECREASED
5%
ANEMIA
5%
PARONYCHIA
5%
BRUISING
5%
SERUM AMYLASE INCREASED
5%
SKIN INFECTION
5%
HYPOALBUMINEMIA
5%
URINARY FREQUENCY
5%
URINARY URGENCY
5%
Behaviour Disturbance
5%
Breast Pain
5%
Conjunctivitis
5%
Creatine Phosphokinase Increased
5%
Ear And Labyrinth Disorders - Other, Impacted Cerumen
5%
Ear Pain
5%
Elevated Amylase
5%
Hypermagnesemia
5%
Hypotension
5%
Infections And Infestations - Other, Covid-19
5%
Infections And Infestations - Other, Gi Viral Infection
5%
Injury, Poisoning And Procedural Complications - Other, Ankle Injury
5%
Injury, Poisoning And Procedural Complications- Other, Scalp Laceration
5%
Investigations - Other, Increased Mean Corpuscular Volume
5%
Investigations - Other, International Normalized Ration Increased
5%
Laryngitis
5%
Localized Edema
5%
Lung Infection
5%
Metabolism And Nutrition Disorders - Other, Decreased Oral Intake
5%
Metabolism Other - Decreased Vitamin D
5%
Metbolism And Nutrition Disorders - Other, Hyperchloremia
5%
Mucositis Oral
5%
Neuropathy
5%
Periodontal Disease
5%
Rash Ezcematoid
5%
Skin And Subcutaneous Disorders - Other, Dry Skin Patches
5%
Skin And Subcutaneous Tissue Disorders - Other, Skin Color Change
5%
Skin And Subcutaneous Tissue Disorders - Other: Blue Lips (Not Cyanosis)
5%
Skin And Subcutaneous Tissue Disorders- Other, New Freckles/Moles
5%
Tooth Infection
5%
Joint Range Of Motion Decreased
100%
80%
60%
40%
20%
0%
Study treatment Arm
Cohort B
Cohort A

COSMIC-312 Trial Design

3Treatment groups
Experimental Treatment
Active Control
Group I: Single-Agent Cabozantinib armExperimental Treatment1 Intervention
Subjects with advanced HCC will receive cabozantinib 60 mg qd
Group II: Experimental armExperimental Treatment2 Interventions
Subjects with advanced HCC will receive cabozantinib 40 mg oral, qd + atezolizumab 1200 mg infusion, q3w
Group III: Control armActive Control1 Intervention
Subjects with advanced HCC will receive sorafenib 400 mg bid (twice a day)
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Cabozantinib
2020
Completed Phase 2
~1080
Atezolizumab
2017
Completed Phase 3
~5860

Find a Location

Who is running the clinical trial?

ExelixisLead Sponsor
117 Previous Clinical Trials
18,714 Total Patients Enrolled
1 Trials studying Liver Cancer

Media Library

Atezolizumab (PD-L1 Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT03755791 — Phase 3
Liver Cancer Research Study Groups: Experimental arm, Control arm, Single-Agent Cabozantinib arm
Liver Cancer Clinical Trial 2023: Atezolizumab Highlights & Side Effects. Trial Name: NCT03755791 — Phase 3
Atezolizumab (PD-L1 Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT03755791 — Phase 3

Frequently Asked Questions

These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

What are the primary conditions that Cabozantinib has been shown to improve?

"While small cell lung cancer (sclc) is the most popular indication for cabozantinib, this medication is also effective in treating other conditions such as malignant neoplasms and hemangiosarcoma."

Answered by AI

How does Cabozantinib affect human health?

"There is both efficacy and safety data available for Cabozantinib, which scored it a 3 on our team's scale."

Answered by AI
Recent research and studies
Future OncologyJournal
Cabozantinib in Combination with Atezolizumab Versus Sorafenib in Treatment-naive Advanced Hepatocellular Carcinoma: COSMIC-312 Phase III Study Design
Kelley, Robin Kate, Jennifer W Oliver, Saswati Hazra, Fawzi Benzaghou, Thomas Yau, Ann-Lii Cheng, and Lorenza Rimassa. 2020. “Cabozantinib in Combination with Atezolizumab Versus Sorafenib in Treatment-naive Advanced Hepatocellular Carcinoma: COSMIC-312 Phase III Study Design”. Future Oncology. Future Medicine Ltd. doi:10.2217/fon-2020-0283.
The Lancet OncologyJournal
Cabozantinib Plus Atezolizumab Versus Sorafenib for Advanced Hepatocellular Carcinoma (COSMIC-312): A Multicentre, Open-label, Randomised, Phase 3 Trial
Kelley, Robin Kate, Lorenza Rimassa, Ann-Lii Cheng, Ahmed Kaseb, Shukui Qin, Andrew X Zhu, Stephen L Chan, et al.. 2022. “Cabozantinib Plus Atezolizumab Versus Sorafenib for Advanced Hepatocellular Carcinoma (COSMIC-312): A Multicentre, Open-label, Randomised, Phase 3 Trial”. The Lancet Oncology. Elsevier BV. doi:10.1016/s1470-2045(22)00326-6.
The Lancet OncologyJournal
Cabozantinib Plus Atezolizumab Versus Sorafenib for Advanced Hepatocellular Carcinoma (COSMIC-312): A Multicentre, Open-label, Randomised, Phase 3 Trial
Kelley, Robin Kate, Lorenza Rimassa, Ann-Lii Cheng, Ahmed Kaseb, Shukui Qin, Andrew X Zhu, Stephen L Chan, et al.. 2022. “Cabozantinib Plus Atezolizumab Versus Sorafenib for Advanced Hepatocellular Carcinoma (COSMIC-312): A Multicentre, Open-label, Randomised, Phase 3 Trial”. The Lancet Oncology. Elsevier BV. doi:10.1016/s1470-2045(22)00326-6.
clinicaltrials.govStudy
Study of Cabozantinib in Combination With Atezolizumab Versus Sorafenib in Subjects With Advanced HCC Who Have Not Received Previous Systemic Anticancer Therapy
2018. "Study of Cabozantinib in Combination With Atezolizumab Versus Sorafenib in Subjects With Advanced HCC Who Have Not Received Previous Systemic Anticancer Therapy". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03755791.
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