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.

Checkpoint Inhibitor

Nivolumab + Ipilimumab for Childhood Cancers

Boston, MA

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.

See full description

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.Check my eligibility

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.See study design

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.

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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.

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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

70%

Fatigue

50%

Headache

45%

Confusional state

45%

Cough

40%

Malignant neoplasm progression

35%

Hemiparesis

35%

Diarrhoea

30%

Gait disturbance

30%

Nausea

30%

Pruritus

25%

Urinary tract infection

25%

Fall

25%

Hyperglycaemia

25%

Muscular weakness

25%

Rash

20%

Constipation

20%

Vomiting

20%

Lethargy

20%

Memory impairment

20%

Urinary incontinence

20%

Dizziness

20%

Nasal congestion

15%

Abdominal pain

15%

Alanine aminotransferase increased

15%

Lymphocyte count decreased

15%

Platelet count decreased

15%

Decreased appetite

15%

Arthralgia

15%

Cognitive disorder

10%

Aspartate aminotransferase increased

10%

Oedema peripheral

10%

Facial paresis

10%

Pyrexia

10%

Candida infection

10%

Depressed level of consciousness

10%

Syncope

10%

Pulmonary embolism

10%

Anaemia

10%

Sinus tachycardia

10%

Anal incontinence

10%

Asthenia

10%

Tooth infection

10%

Upper respiratory tract infection

10%

Lipase increased

10%

Paraesthesia

10%

Psychomotor skills impaired

10%

Seizure

10%

Agitation

10%

Anxiety

10%

Disorientation

10%

Dehydration

10%

Hypoalbuminaemia

10%

Hypokalaemia

10%

Hyponatraemia

10%

Aphasia

10%

Dysarthria

10%

Dyspnoea

10%

Rash maculo-papular

Dermatitis acneiform

Dysphagia

Oedema

Pain

Cardio-respiratory arrest

Autoimmune thyroiditis

Pneumonia

Hip fracture

White blood cell count decreased

Enterocolitis infectious

Tumour flare

Brain oedema

Cerebrovascular accident

Ischaemic stroke

Mental status changes

Aspiration

Herpes zoster

Haemorrhage intracranial

Hypoxia

Pneumonitis

Respiratory distress

Atrial fibrillation

Cushingoid

Hyperthyroidism

Hypothyroidism

Dry eye

Eyelid ptosis

Visual field defect

Visual impairment

Dyspepsia

Oral candidiasis

Stomatitis

Chills

Amylase increased

Blood alkaline phosphatase increased

Blood bilirubin increased

Weight decreased

Weight increased

Tremor

Vasogenic cerebral oedema

Depression

Insomnia

Pollakiuria

Hypocalcaemia

Proteinuria

Back pain

Myalgia

Amnesia

Ataxia

Balance disorder

Dysphonia

Dry skin

Deep vein thrombosis

Hypertension

Hypotension

Colitis

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 1b: Arm N3+I1

Cohort 1: Arm N3

Cohort 1: Arm N1+I3

Cohort 2: Arm N3

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

Cohort 2: Arm B

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

Part B Cohort 1d: Arm N3+RT

Part A Cohort 1d: Arm N3+RT

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

2014

Completed Phase 3

~3880

Ipilimumab

2015

Completed Phase 3

~3380

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.