What side effects are associated with this type of intervention?

Common treatments for mesothelioma, such as low dose cyclophosphamide combined with sub-ablative radiation, can lead to a range of side effects. Cyclophosphamide, a DNA cross-linking agent, is associated with myelosuppression, gastrointestinal toxicities, fatigue, and potential long-term risks like secondary myeloid neoplasms. Sub-ablative radiation therapy can cause localized side effects such as skin reactions, pneumonitis, and potential heart damage if the heart is exposed to significant radiation doses. Combining these treatments may increase the risk of cumulative toxicities, necessitating careful monitoring and management.

What prior FDA approvals exist?

The FDA has approved several treatments for mesothelioma, primarily focusing on chemotherapy regimens. The combination of pemetrexed and cisplatin is a standard first-line treatment for unresectable mesothelioma, showing efficacy in prolonging overall survival. Additionally, the integration of chemotherapy with surgery and radiation therapy has been explored in clinical trials. While low dose cyclophosphamide with sub-ablative radiation is not specifically mentioned, the use of DNA cross-linking agents like cisplatin in combination with radiation therapy is a common approach in mesothelioma treatment.

What other types of research exist?

Promising novel alternatives for mesothelioma patients include: 1) Tremelimumab combined with Durvalumab, which has shown activity in mesothelioma patients in the NIBIT-MESO-1 study. 2) Nivolumab, either alone or in combination with Ipilimumab, as demonstrated in the IFCT-1501 MAPS2 and INITIATE trials. 3) Pembrolizumab, which has shown clinical safety and activity in the KEYNOTE-028 trial. These immunotherapy options represent potential advancements in the treatment of mesothelioma.

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Alkylating agents

Chemotherapy + Immunotherapy for Rectal Cancer

Phase 2

Recruiting

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 untreated mesothelioma

Body weight >30 kg

Must not have

Previous thoracic irradiation

Active or prior documented autoimmune or inflammatory disorders

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to five years

Awards & highlights

Approved for 20 Other Conditions

No Placebo-Only Group

Summary

This trial tests a treatment for cancer patients undergoing surgery. It uses low dose chemotherapy and radiation to weaken the cancer, followed by immunotherapy drugs to help the immune system fight any remaining cancer cells.

Who is the study for?

The SMARTEST trial is for adults over 18 with previously untreated mesothelioma, stages I-III. Participants must be fit for surgery, have good organ function, weigh more than 30 kg, and have a life expectancy of at least 12 weeks. They should not have had recent cancer treatments or other clinical trials that could interfere.

What is being tested?

This phase II trial tests low dose cyclophosphamide with radiation before surgery (Arm A) against radiation alone (Arm B). After surgery, eligible patients from both arms receive tremelimumab-durvalumab to assess safety and effectiveness.

What are the potential side effects?

Potential side effects include immune-related reactions due to tremelimumab-durvalumab therapy such as inflammation in various organs, fatigue, digestive issues and potential increased risk of infections.

Eligibility Criteria

Inclusion Criteria

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

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I have mesothelioma and have not received any treatment for it.

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I weigh more than 30 kilograms.

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My cancer is at stage I, II, or III based on specific scans.

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I am 18 years old or older.

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I am fully active or can carry out light work.

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My condition is confirmed mesothelioma through tissue analysis.

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My tumor can be safely biopsied.

Exclusion Criteria

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

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I have had radiation therapy to the chest area before.

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I have or had an autoimmune or inflammatory disorder.

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My cancer has spread to distant parts of my body, including possibly the brain or spine.

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I have tested positive for HIV or have active tuberculosis.

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I do not have an active hepatitis infection.

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I am not currently on any cancer treatments like chemotherapy or hormone therapy.

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I have received an organ transplant from another person.

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I have had cancer before.

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I have had cancer spread to the lining of my brain and spinal cord.

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I have a serious illness like heart or lung disease that prevents me from getting radiation therapy.

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I do not have any unmanaged ongoing illnesses.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to five years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to five years

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

CD8 TILs density / gross tumor volume (GTV)

Secondary study objectives

Survival

Other study objectives

Proportional change in circulating CD8 RA+ effector memory T cells, Proportional change in circulating CD4 RA+ effector memory T cells

Side effects data

From 2023 Phase 2 trial • 27 Patients • NCT04002401

88%

Pyrexia

65%

Neutrophil count decreased

62%

Nausea

58%

Hypotension

50%

Anaemia

46%

Headache

38%

Fatigue

38%

Decreased appetite

35%

Confusional state

31%

Tachycardia

31%

Diarrhoea

31%

Hypokalaemia

27%

Constipation

27%

Hypophosphataemia

27%

Back pain

23%

B-cell lymphoma

23%

Dizziness

23%

Tremor

23%

Platelet count decreased

23%

White blood cell count decreased

19%

Cough

19%

Agitation

19%

Hyponatraemia

19%

Neutropenia

19%

Tachypnoea

19%

Hypogammaglobulinaemia

19%

Oedema peripheral

15%

Hypomagnesaemia

15%

Thrombocytopenia

15%

Alanine aminotransferase increased

15%

Sinus tachycardia

15%

Chills

15%

Dyspnoea

15%

Dysphagia

12%

Aspartate aminotransferase increased

12%

Pain

12%

Myalgia

12%

Hypertension

12%

Hyperglycaemia

12%

Hypoxia

12%

Vomiting

12%

Abdominal pain

12%

Peripheral sensory neuropathy

12%

Arthralgia

12%

Covid-19

12%

Malaise

Acute myeloid leukaemia

Dysuria

Muscular weakness

Oral candidiasis

Blood creatinine increased

Hyperhidrosis

Sepsis

Pancytopenia

Eye pain

Lymphocyte count decreased

Asthenia

Urinary tract infection

Somnolence

Encephalopathy

Insomnia

Pneumonia

Gait disturbance

Aphasia

Pleural effusion

Depression

Embolism

Syncope

Respiratory failure

Febrile neutropenia

Covid-19 pneumonia

100%

80%

60%

40%

20%

Study treatment Arm

Axicabtagene Ciloleucel and Rituximab Combination

Awards & Highlights

Approved for 20 Other Conditions

This treatment demonstrated efficacy for 20 other conditions.

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: Radiation+Drug (Arm A)Experimental Treatment3 Interventions

sub-ablative radiation plus low dose cyclophosphamide followed by surgery and adjuvant immunotherapy

Group II: Radiation alone (Arm B)Experimental Treatment2 Interventions

sub-ablative radiation alone followed by surgery and adjuvant immunotherapy

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cyclophosphamide

FDA approved

Tremelimumab

Not yet FDA approved

Durvalumab

FDA approved

0 / 18Eligibility 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

Cyclophosphamide, an alkylating agent, works by cross-linking DNA strands, thereby preventing cell division and leading to cell death. Sub-ablative radiation therapy delivers lower doses of radiation to partially damage tumor cells, making them more susceptible to subsequent treatments and immune system attack. These mechanisms are crucial for mesothelioma patients as they target the cancer cells' ability to proliferate and survive, potentially improving treatment outcomes and survival rates.

Patterns of subsequent malignancies after Hodgkin lymphoma in children and adults.Phase I clinical trial of O6-benzylguanine and topical carmustine in the treatment of cutaneous T-cell lymphoma, mycosis fungoides type.Effect of prior chemotherapy on hematopoietic stem cell mobilization.