What is the mechanism of action of this treatment?

Atezolizumab, an immunotherapy with monoclonal antibodies, works by targeting the PD-L1 protein to enhance the immune system's ability to attack cancer cells. Cabozantinib, a tyrosine kinase inhibitor, blocks enzymes necessary for cancer cell growth and spread. These treatments are significant for Osteosarcoma patients as they provide targeted strategies to control tumor progression and metastasis, offering hope for improved outcomes when conventional therapies are insufficient.

What side effects are associated with this type of intervention?

Atezolizumab, an immunotherapy monoclonal antibody, can cause side effects such as fatigue, diarrhea, nausea, decreased appetite, and immune-related adverse events like pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. Cabozantinib, a tyrosine kinase inhibitor, is associated with side effects including diarrhea, fatigue, nausea, decreased appetite, palmar-plantar erythrodysesthesia syndrome, hypertension, vomiting, weight loss, and constipation. Both treatments can lead to significant but manageable toxicities that require monitoring and supportive care.

What prior FDA approvals exist?

As of now, there are no FDA-approved treatments specifically for osteosarcoma that are directly analogous to atezolizumab (an immunotherapy with monoclonal antibodies) or cabozantinib (a tyrosine kinase inhibitor). However, the use of immunotherapy and tyrosine kinase inhibitors in other cancers has shown promise, and ongoing clinical trials, such as the TACOS study, are investigating their efficacy in osteosarcoma. This study aims to determine if the combination of atezolizumab and cabozantinib can help control recurrent or metastatic osteosarcoma.

What other types of research exist?

Promising alternatives to Atezolizumab and Cabozantinib for osteosarcoma patients include Pembrolizumab (an immune checkpoint inhibitor) and Axitinib (a tyrosine kinase inhibitor). Pembrolizumab has shown activity in various sarcomas, and Axitinib has been effective in combination with Pembrolizumab for advanced sarcomas. Additionally, Pazopanib, another tyrosine kinase inhibitor, has demonstrated efficacy in treating advanced soft tissue sarcomas and could be considered for osteosarcoma.

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PD-L1 Inhibitor

Atezolizumab + Cabozantinib for Osteosarcoma

Phase 2

Recruiting

Led By John A Livingston, MD

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

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

Must have

Eastern Cooperative Oncology Group (ECOG) of 0, 1 or 2. Use Karnofsky >= 50 for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age

Platelet count >= 100 x 10^9/L (100,000/uL) without transfusion (obtained within 14 days prior to initiation of study treatment)

Must not have

Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected serum calcium > upper limit of normal [ULN])

History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests atezolizumab and cabozantinib in young patients with hard-to-treat osteosarcoma. Atezolizumab helps the immune system attack cancer, while cabozantinib blocks cancer cell growth. Cabozantinib is approved for various cancers, including kidney, liver, and thyroid cancers.

Who is the study for?

Adolescents and young adults aged 12 or older with recurrent or metastatic osteosarcoma, who have tried conventional therapies without success. Participants must have measurable disease, be able to provide a tumor specimen for research, and meet specific health criteria including organ function tests. They should not be HIV positive and must agree to use effective contraception.

What is being tested?

The trial is testing the combination of Atezolizumab (an immunotherapy drug) and Cabozantinib (a drug that blocks tumor growth enzymes) in patients with advanced osteosarcoma. The study aims to see if this drug combo can control cancer better than current treatments.

What are the potential side effects?

Possible side effects include immune-related reactions, liver issues, high blood pressure, fatigue, diarrhea, mouth sores, hand-foot syndrome (redness and pain on palms or soles), decreased appetite, weight loss, nausea/vomiting.

Eligibility Criteria

Inclusion Criteria

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

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I am mostly active and can care for myself despite my illness.

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My platelet count is at least 100,000 without needing a transfusion.

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My diagnosis of bone cancer is confirmed by tissue examination.

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My cancer did not respond or has returned after treatment with specific chemotherapy drugs.

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I am 12 years old or older.

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My cancer has spread and cannot be removed by surgery.

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My body surface area is at least 1 square meter.

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My kidney function, measured by creatinine clearance, is sufficient.

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My white blood cell count is healthy without needing medication.

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My liver tests, AST and ALT, are within normal limits.

Exclusion Criteria

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

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My calcium levels are normal and not causing symptoms.

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I have a history of specific lung conditions or signs of lung inflammation on a CT scan.

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I have not had significant bleeding or coughed up more than half a teaspoon of blood in the last 3 months.

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My high blood pressure is not controlled despite treatment.

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I have lung lesions or disease in my airways.

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I have had leptomeningeal disease.

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I frequently need procedures to remove excess fluid from my body.

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I cannot swallow pills.

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My liver function is significantly impaired.

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I am currently taking certain blood thinners.

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I have pain from my cancer that isn't relieved by treatment.

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I haven't had major heart issues or strokes in the last 3 months.

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My cancer is growing into or around major blood vessels.

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I have been treated with cabozantinib before.

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I have symptoms of underactive thyroid that aren't treated.

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I have a GI disorder that could lead to holes or abnormal connections in my digestive tract.

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My heart's electrical activity (QTcF) is not over 500 ms.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 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

Progression-free survival (PFS)

Secondary study objectives

Incidence of adverse events

Objective response rate

Overall survival (OS)

+1 more

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%

PALMAR-PLANTAR ERYTHRODYSESTHESIA SYNDROME

36%

HEADACHE

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

Allergic Rhinitis

Hypotension

Muscle Weakness Lower Limb

Hypertension

SERUM AMYLASE INCREASED

Investigations - Other, Eosinophilia

Sore Throat

HEMATURIA

ANXIETY

Hypermagnesemia

Rash Ezcematoid

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

Gastrointestinal Disorders - Other, Dental Pain

Peripheral Motor Neuropathy

Tachycardia

URINARY FREQUENCY

Conjunctivitis

Neuropathy

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

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: Treatment (atezolizumab, cabozantinib)Experimental Treatment2 Interventions

Patients receive atezolizumab IV over 60 minutes on day 1 and cabozantinib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Atezolizumab

2016

Completed Phase 3

~5860

Cabozantinib

2020

Completed Phase 2

~1760

0 / 27Eligibility 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

Atezolizumab, an immunotherapy with monoclonal antibodies, works by targeting the PD-L1 protein to enhance the immune system's ability to attack cancer cells. Cabozantinib, a tyrosine kinase inhibitor, blocks enzymes necessary for cancer cell growth and spread. These treatments are significant for Osteosarcoma patients as they provide targeted strategies to control tumor progression and metastasis, offering hope for improved outcomes when conventional therapies are insufficient.

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