What side effects are associated with this type of intervention?

The most common treatments for Malignant Rhabdoid Tumor involving PD-1 inhibitors (such as Nivolumab) and CTLA-4 inhibitors (such as Ipilimumab) can lead to a range of side effects. These include immune-related adverse events such as colitis, hepatitis, dermatitis, endocrinopathies (like thyroiditis and hypophysitis), and pneumonitis. Other common side effects are fatigue, rash, diarrhea, and pruritus. Severe side effects may necessitate the use of immunosuppressive medications like corticosteroids to manage these immune-related toxicities.

What prior FDA approvals exist?

There is no specific mention of prior FDA approvals for the treatment of Malignant Rhabdoid Tumor using Nivolumab and Ipilimumab or similar PD-1 and CTLA-4 inhibitors in the provided context. However, these drugs are being studied in clinical trials for their potential efficacy in treating various cancers, including those with aggressive and rare subtypes. Broadly, immune checkpoint inhibitors like Nivolumab (a PD-1 inhibitor) and Ipilimumab (a CTLA-4 inhibitor) have been approved for other cancers such as melanoma and renal cell carcinoma, showing promise in enhancing the immune system's ability to fight cancer.

What other types of research exist?

Promising novel alternatives to Nivolumab and Ipilimumab for Malignant Rhabdoid Tumor patients include combination therapies involving PD-1/PD-L1 inhibitors with IDO1 inhibitors, as these have shown potential in related sarcomatoid/rhabdoid cancers. Additionally, ongoing research into other immune checkpoint inhibitors and targeted therapies, such as those targeting specific genetic mutations or tumor microenvironment factors, may offer new treatment options. Patients should discuss participation in clinical trials exploring these novel therapies with their oncologist.

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Checkpoint Inhibitor

Nivolumab + Ipilimumab for Childhood Cancers

Phase 2

Recruiting

Led By Suzanne Forrest, MD

Research Sponsored by Dana-Farber Cancer Institute

Eligibility Criteria Checklist

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

Must have

Participants must have tumor assessment at original diagnosis or relapse showing specific molecular and immunohistochemical characteristics

Participants must have relapsed or refractory disease with no standard treatment options available

Must not have

Active autoimmune disease requiring systemic treatment

Prior solid organ transplantation

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 3 years

Awards & highlights

No Placebo-Only Group

Summary

This study is evaluating whether two immunotherapy drugs may be effective for treating certain types of cancer.

Who is the study for?

This trial is for children and young adults with specific INI1-negative tumors, including kidney tumors and various sarcomas. Participants must have relapsed or refractory disease without standard treatment options, measurable disease, good performance status, recovered from prior treatments' effects, adequate organ function, and no recent vaccines.

What is being tested?

The study tests the combination of two immunotherapy drugs: Nivolumab and Ipilimumab. These are given together to see if they can effectively treat certain aggressive cancers that lack a protein called INI1.

What are the potential side effects?

Nivolumab and Ipilimumab may cause immune-related side effects such as inflammation in organs like the lungs (pneumonitis), liver problems, skin reactions, hormone gland issues (like thyroid dysfunction), digestive tract symptoms (colitis), fatigue, and infusion reactions.

Eligibility Criteria

Inclusion Criteria

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

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My tumor has specific genetic and protein markers.

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My condition has returned or didn't respond to treatment, and no standard treatments are available.

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My cancer type was confirmed through a biopsy at diagnosis or relapse.

Exclusion Criteria

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

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I am on medication for an autoimmune disease.

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I have had a solid organ transplant.

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I have been treated with specific medications before.

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I am not taking any steroid medications.

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I have a history of HIV, hepatitis B, or hepatitis C.

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I do not have any uncontrolled illnesses or active infections.

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I have had or currently have lung inflammation treated with steroids.

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

Objective Overall Response Rate (Stratum 1)

Objective Overall Response Rate (Stratum 2)

Secondary study objectives

Disease control rate at 12 months

Occurrence of toxicities (Grade 3-5 per CTCAE)

Overall survival (OS)

+1 more

Side effects data

From 2024 Phase 3 trial • 529 Patients • NCT02017717

80%

Fatigue

70%

Diarrhoea

70%

Headache

40%

Vomiting

40%

Aspartate aminotransferase increased

40%

Rash maculo-papular

40%

Alanine aminotransferase increased

40%

Lipase increased

30%

Partial seizures

30%

Hemiparesis

30%

Gait disturbance

30%

Fall

30%

Cough

30%

Dry skin

30%

Amylase increased

30%

Nausea

30%

Confusional state

20%

Malignant neoplasm progression

20%

Pyrexia

20%

Candida infection

20%

Mucosal infection

20%

Decreased appetite

20%

Back pain

20%

Dysphonia

20%

Hypotension

20%

Colitis

20%

Hyperthyroidism

20%

Oedema peripheral

20%

Muscular weakness

20%

Hypothyroidism

10%

Tinnitus

10%

Cushingoid

10%

Diabetic ketoacidosis

10%

Procedural haemorrhage

10%

Blood bilirubin increased

10%

Bradycardia

10%

Sinus tachycardia

10%

Hyperglycaemia

10%

Hypocalcaemia

10%

Neck pain

10%

Brain oedema

10%

Hydrocephalus

10%

Lethargy

10%

Seizure

10%

Hypertension

10%

Palpitations

10%

Cheilitis

10%

Presyncope

10%

Face oedema

10%

Oedema

10%

Conjunctivitis

10%

Enterocolitis infectious

10%

Oral candidiasis

10%

Pneumonia

10%

Sinusitis

10%

Staphylococcal infection

10%

Blood alkaline phosphatase increased

10%

Spinal pain

10%

Tremor

10%

Dizziness

10%

Dysarthria

10%

Urinary retention

10%

Dyspnoea exertional

10%

Nasal congestion

10%

Pneumonitis

10%

Dermatitis

10%

Erythema

10%

Rash

10%

Klebsiella infection

10%

Hypomagnesaemia

10%

Syncope

10%

Haemorrhage intracranial

10%

Pancreatitis

10%

Cholecystitis

10%

Upper respiratory tract infection

10%

Acute kidney injury

10%

Dermatitis bullous

10%

Lymphopenia

10%

Optic nerve disorder

10%

Visual impairment

10%

Dehydration

10%

Hypokalaemia

10%

Scoliosis

10%

Cognitive disorder

10%

Memory impairment

10%

Hallucination

10%

Insomnia

10%

Irritability

10%

Urinary incontinence

10%

Dyspnoea

10%

Dermatitis acneiform

10%

Pelvic venous thrombosis

10%

Sepsis

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 1: Arm N1+I3

Cohort 2: Arm B

Part A Cohort 1c: Arm N3+RT+TMZ

Part A Cohort 1d: Arm N3+RT

Part B Cohort 1c: Arm N3+RT+TMZ

Part B Cohort 1d: Arm N3+RT

Cohort 1: Arm N3

Cohort 1b: Arm N3+I1

Cohort 2: Arm N3

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Group I: Solid Tumor (Stratum 1)Experimental Treatment2 Interventions

* Patients will receive combination therapy with nivolumab at a predetermined dose and ipilimumab at a predetermined dose day 1 of a 21-day cycle for 4 cycles * Starting with cycle 5, patients will receive nivolumab monotherapy at a predetermined dose on day 1 and day 15 of a 28-day cycle * Patients with INI1-negative relapsed or refractory extracranial solid tumors

Group II: CNS (Stratum 2)Experimental Treatment2 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Nivolumab

2015

Completed Phase 3

~4010

Ipilimumab

2015

Completed Phase 3

~3420

0 / 10Eligibility 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

Nivolumab and Ipilimumab are immunotherapy drugs that work by inhibiting immune checkpoints, specifically PD-1 and CTLA-4, respectively. Nivolumab blocks the PD-1 receptor on T-cells, preventing cancer cells from evading immune detection. Ipilimumab inhibits CTLA-4, enhancing T-cell activation and proliferation. These mechanisms are crucial for Malignant Rhabdoid Tumor patients because these tumors often evade the immune system. By blocking these checkpoints, Nivolumab and Ipilimumab can potentially restore the immune system's ability to recognize and attack tumor cells, offering a promising therapeutic approach for this aggressive cancer.

ACCELERATE and European Medicines Agency Paediatric Strategy Forum for medicinal product development of checkpoint inhibitors for use in combination therapy in paediatric patients.Immunotherapy of heterogenous sarcomas: questions and strategies.Checkpoint inhibition of PD-L1 and CTLA-4 in a child with refractory acute leukemia.