What side effects are associated with this type of intervention?

Common treatments for Head and Neck Squamous Cell Carcinoma (HNSCC) include radiation therapy, chemoradiation, and targeted therapies. Radiation therapy can cause mucositis, dysphagia, and late toxicities such as fibrosis and osteonecrosis. Chemoradiation, particularly with cisplatin, adds risks of nephrotoxicity, ototoxicity, and increased mucositis. Targeted therapies like cetuximab may lead to skin reactions, infusion reactions, and hypomagnesemia. These side effects vary in severity and frequency, impacting the patient's quality of life and requiring careful management.

What prior FDA approvals exist?

The FDA has approved several treatments for Head and Neck Squamous Cell Carcinoma (HNSCC). Notably, immunotherapy drugs such as nivolumab and pembrolizumab, which target the programmed death protein 1 (PD-1), have shown significant clinical activity and are approved for patients who have previously been treated with platinum-based chemotherapy. Additionally, cetuximab, an anti-EGFR monoclonal antibody, is approved for use in combination with platinum-based chemotherapy and fluorouracil, or as a monotherapy in certain cases. These treatments represent significant advancements in the management of HNSCC, particularly for patients with recurrent or metastatic disease.

What other types of research exist?

Promising alternatives to AZD2936 for HNSCC patients include AZD8055 and AZD4547. AZD8055 is a dual mTORC1/2 inhibitor that has shown efficacy in inhibiting HNSCC cell growth in vivo and in vitro. AZD4547 targets Fibroblast Growth Factor Receptors (FGFR) and has demonstrated significant tumor growth delay when combined with radiation, suggesting its potential as a radiosensitizer.

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Monoclonal Antibodies

AZD2936 for Head and Neck Cancer (MERIDIAN Trial)

Phase 2

Recruiting

Led By Lillian Siu, MD

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

High-risk HPV negative or positive LA-HNSCC patients

Weight ≥ 35 kg

Must not have

Active or prior documented autoimmune or inflammatory disorders

Receipt of live attenuated vaccine within 30 days prior to study intervention

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests AZD2936, a new drug, in patients with high-risk head and neck cancer who still have cancer DNA in their blood. The drug aims to clear out any leftover cancer cells by targeting the cancer DNA found in the blood.

Who is the study for?

This trial is for adults with advanced head and neck squamous cell carcinoma (LA-HNSCC) who have detectable cancer DNA in their blood after initial treatment. They must be able to perform daily activities with ease or with some limitation (ECOG 0-1), weigh at least 35 kg, and have a life expectancy of over 12 weeks.

What is being tested?

The study tests AZD2936's ability to clear molecular residual disease (MRD), which is cancer DNA found in the blood post-treatment, in patients with high-risk LA-HNSCC. It's an open-label phase II trial where around 200 participants will receive this experimental therapy.

What are the potential side effects?

While specific side effects of AZD2936 are not provided here, similar drugs often cause fatigue, nausea, skin reactions, and increased risk of infections. Side effects can vary based on individual patient factors.

Eligibility Criteria

Inclusion Criteria

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

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My head or neck cancer is either high-risk HPV positive or negative.

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I weigh at least 35 kilograms.

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My cancer in the head or neck area has been confirmed by lab tests.

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I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

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

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I have or had an autoimmune or inflammatory disorder.

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I have not received a live vaccine in the last 30 days.

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My cancer has spread to distant parts of my body.

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My cancer is in the head or neck, but not in the areas doctors usually specify.

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I have had another type of cancer in the past.

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I do not have any unmanaged ongoing illnesses.

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I do not have an active infection like TB or hepatitis.

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I have no ongoing major side effects from previous cancer treatments.

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

Efficacy (in terms of ctDNA clearance) of AZD2936 compared to observation (Standard of Care, SOC) in LA-HNSCC patients who have MRD (MRD+) after definitive treatment.

Secondary study objectives

Efficacy (in terms of MRD control) of AZD2936 compared to observation (SOC) in MRD+ LA-HNSCC patients after definitive treatment.

Efficacy (in terms of delaying or preventing radiological recurrence of disease or death) of AZD2936 compared to observation (SOC) in MRD+ LA-HNSCC patients after definitive treatment.

Efficacy (in terms of median DFS and OS) of AZD2936 compared to observation (SOC) in MRD+ LA-HNSCC patients after definitive treatment.

+1 more

Other study objectives

Correlation between radiological response and changes in quantitative bespoke ctDNA and HPV DNA measurements.

Cost effectiveness of the experimental arm vs observation at various time through the study using the EQ-5D-5L.

Health related quality of life at various time points throughout the study using the FACT-ICM and EORTC HN43 tool.

+6 more

Side effects data

From 2013 Phase 2 trial • 86 Patients • NCT01256385

75%

Fatigue

65%

Anemia

48%

Hyperglycemia

43%

Lymphocyte count decreased

38%

Anorexia

35%

Platelet count decreased

35%

Constipation

35%

Cough

35%

Nausea

30%

Pain

30%

Mucositis oral

28%

Dyspnea

28%

White blood cell decreased

28%

Hypoalbuminemia

25%

Alanine aminotransferase increased

25%

Cholesterol high

25%

Hypertriglyceridemia

23%

Dysphagia

20%

Depression

20%

Fever

20%

Hypophosphatemia

20%

Weight loss

18%

Alkaline phosphatase increased

18%

Non-cardiac chest pain

18%

Aspartate aminotransferase increased

18%

Insomnia

18%

Headache

18%

Hyponatremia

18%

Hypocalcemia

18%

Hypokalemia

15%

Edema face

15%

Vomiting

15%

Creatinine increased

15%

Neck pain

15%

Peripheral sensory neuropathy

13%

Infections and infestations - Other

13%

Diarrhea

13%

Dysgeusia

13%

Rash acneiform

13%

Rash maculo-papular

10%

Neutrophil count decreased

10%

Arthralgia

10%

Dizziness

10%

Edema limbs

Anxiety

Oral dysesthesia

Respiratory failure

Pneumonitis

Pruritus

Facial pain

Back pain

Dry mouth

Dry skin

Hypertension

INR increased

Neck edema

Allergic rhinitis

Pleural effusion

General disorders and administration site conditions - Other

Hypernatremia

Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other

Skin infection

Dyspepsia

Ear pain

Epistaxis

Gastroesophageal reflux disease

Generalized muscle weakness

Hypomagnesemia

Leukocytosis

Lung infection

Lymphedema

Sore throat

Tumor pain

Urinary frequency

Hearing impaired

Sinusitis

Chills

Dehydration

Hypercalcemia

Hyperkalemia

Myalgia

Papulopustular rash

Alopecia

Oral pain

Vertigo

Tracheostomy site bleeding

Pharyngeal hemorrhage

Laryngeal obstruction

Anorectal infection

Hypoxia

Pleural infection

Pleuritic pain

Pneumothorax

Respiratory, thoracic and mediastinal disorders - Other

Stridor

Postnasal drip

Skin and subcutaneous tissue disorders - Other

Skin ulceration

Eye disorders - Other

Heart failure

Tracheal hemorrhage

Blurred vision

Hypotension

Palmar-plantar erythrodysesthesia syndrome

Peripheral motor neuropathy

100%

80%

60%

40%

20%

Study treatment Arm

Arm B (Temsirolimus)

Arm A (Cetuximab and Temsirolimus)

Awards & Highlights

No Placebo-Only Group

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

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: MRD positive Cohort - Arm A (treatment)Experimental Treatment1 Intervention

Dose formulation- AZD2936 is supplied as a liquid drug product in a 20R vial containing 750 mg (nominal) of active AZD2936. The solution contains 50 mg/mL AZD2936 in 20 mM L-histidine/L- histidine-hydrochloride, 240 mM sucrose, 0.04% (w/v) poloxamer 188, at pH 6.0. Unit dose strength(s)- 750 mg/vial (50 mg/mL) Dosage levels- 750mg administered Q3W Route of administration- IV infusion over 1 hour

Group II: MRD negative CohortActive Control1 Intervention

Observation

Group III: MRD positive Cohort - Arm B (observation)Active Control1 Intervention

Observation

0 / 12Eligibility 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

Common treatments for Head and Neck Squamous Cell Carcinoma (HNSCC) include radiotherapy, chemotherapy, and targeted molecular therapies. Radiotherapy damages the DNA of cancer cells, leading to their death. Chemotherapy agents like cisplatin and docetaxel disrupt cell division and induce apoptosis. Targeted therapies, such as EGFR inhibitors, block specific pathways that cancer cells use to grow and proliferate. These mechanisms are important for HNSCC patients as they help in selecting effective treatments, improving survival rates, and minimizing side effects.

Analysis of Laser Therapy Effects on Squamous Cell Carcinoma Patients: A System Biology Study.Inhibition of SphK1 reduces radiation-induced migration and enhances sensitivity to cetuximab treatment by affecting the EGFR / SphK1 crosstalk.Molecular targeted therapies in all histologies of head and neck cancers: an update.