What side effects are associated with this type of intervention?

Common treatments for colorectal cancer, such as oxaliplatin-based chemotherapy and fluorouracil (FU), are associated with several side effects. Oxaliplatin can cause neuropathy, which may persist in some patients even after discontinuation. Fluorouracil is linked to gastrointestinal issues like diarrhea, nausea, and stomatitis, as well as fatigue and partial alopecia. Cetuximab, when used in combination therapies, can lead to severe skin reactions, hypomagnesemia, and infusion-related reactions. These side effects highlight the importance of monitoring and managing treatment-related toxicities in colorectal cancer patients.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of colorectal cancer that modulate signaling pathways. Cetuximab, an EGFR inhibitor, is one such drug, often used in combination with chemotherapy. Another example is bevacizumab, an anti-VEGF monoclonal antibody, which inhibits angiogenesis. Additionally, regorafenib, a multi-kinase inhibitor, targets various kinases involved in tumor growth and progression. These treatments, like NT219, aim to disrupt critical pathways that cancer cells use for survival and proliferation.

What other types of research exist?

Promising novel alternatives to NT219 for colorectal cancer patients include: 1) LY2835219 (a CDK4/6 inhibitor) which has shown efficacy in inducing cell-cycle arrest and tumor growth inhibition in preclinical models. 2) The combination of DT-13 and Topotecan, which targets the NM IIA/EGFR/HK II axis and has shown potential in inhibiting aerobic glycolysis in gastric carcinoma cells, suggesting possible applicability in colorectal cancer. 3) 1-benzylidene-3,4-dihydronaphthalen-2-one, a microtubule-targeting agent that has demonstrated significant tumor growth inhibition in colon cancer models.

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Monoclonal Antibodies

NT219 + Cetuximab for Head and Neck Cancer

Phase 1 & 2

Waitlist Available

Research Sponsored by TyrNovo Ltd.

Eligibility Criteria Checklist

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

Must have

ECOG performance status score of 0 or 1

Subject with previously treated advanced solid tumors (Portion 1) or recurrent and/or metastatic squamous cell carcinoma of the head and neck (Portion 2 and 3) or colorectal adenocarcinoma, stage III/IV (Portion 2) that must have failed or not be a candidate for available standard of care therapies with documented progression/intolerance following the most recent prior regimen;

Must not have

Known hypersensitivity to epidermal growth factor receptor (EGFR), Janus kinase (JAK), or signal transducer and activator of transcription (STAT) antagonists/inhibitors, or inactive ingredients of NT219

Cardiovascular (e.g., History of long QT syndrome, NYHA) Class III or IV cardiac disease)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 24 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new drug, NT219, alone and with an existing treatment, ERBITUX®, in adults whose cancer has returned or spread. NT219 aims to stop cancer growth, and when combined with ERBITUX®, it may be more effective.

Who is the study for?

Adults with advanced solid tumors, head and neck cancer, or colorectal cancer that's worsened after treatment can join. They must have at least one measurable tumor lesion, be in fairly good health (ECOG score of 0 or 1), and not have had recent major surgery or other treatments. Women who can bear children must test negative for pregnancy and agree to use birth control.

What is being tested?

The trial is testing NT219 alone and combined with ERBITUX® (Cetuximab) in a two-part study: first to find the right dose (dose escalation) then to see how well it works (expansion phase). It aims to evaluate safety, tolerability, how the body processes the drugs, their effects on tumors, and overall effectiveness.

What are the potential side effects?

Possible side effects include reactions related to drug infusion, changes in liver enzymes which may indicate liver issues, fatigue from low red blood cell counts (anemia), potential kidney function changes indicated by creatinine clearance levels, as well as general risks associated with chemotherapy such as nausea.

Eligibility Criteria

Inclusion Criteria

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

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

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My advanced cancer has not improved with standard treatments.

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I haven't taken any cancer treatment drugs or experimental agents for at least 4 weeks, or 6 weeks for specific immunotherapies, and any side effects I had are now minimal.

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My brain cancer has not grown or spread recently.

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I have at least one tumor that can be measured and has grown since my last cancer treatment.

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

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My kidneys work well, with a creatinine clearance over 60 mL/min.

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I have advanced cancer that standard treatments no longer control.

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I have at least one tumor that can be measured and has grown since my last cancer treatment.

Exclusion Criteria

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

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I am allergic to certain cancer drugs or ingredients in NT219.

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I do not have severe heart disease.

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I have received an organ transplant from another person.

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I have lost more than 10% of my weight in the last 2 months.

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I do not have an uncontrolled HIV, HBV, or HCV infection.

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I have active brain or spinal cord disease from cancer.

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I have severe lung disease.

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I do not have an active infection or a history of tuberculosis.

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I have not had major surgery in the last 4 weeks.

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I have untreated brain metastases.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 24 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Part 1: Incidence of treatment emergent adverse events

Part 2: Incidence of treatment emergent adverse events

Part 3: Objective Response Rate

Secondary study objectives

Area under the plasma concentration curve [AUC]

Maximum plasma concentration [Cmax]

Plasma clearance [Cl]

+2 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%

Insomnia

18%

Non-cardiac chest pain

18%

Aspartate aminotransferase increased

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

Vertigo

Oral pain

Alopecia

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

Group I: Expansion cohort of NT219 in combination with ERBITUX®Experimental Treatment1 Intervention

Group II: Dose escalation of NT219 in combination with ERBITUX®Experimental Treatment1 Intervention

Group III: Dose escalation of NT219 as a single agentExperimental Treatment1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

NT219

2020

Completed Phase 2

~60

NT219 and ERBITUX® - Dose Escalation

2020

Completed Phase 2

~60

NT219 and ERBITUX® - Expansion

2020

Completed Phase 2

~60

0 / 19Eligibility 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 colorectal cancer often target key signaling pathways involved in cancer cell growth and survival. NT219, for example, modulates signaling pathways such as IRS1/2 and STAT3, which are crucial for cancer cell proliferation and resistance to apoptosis. Similarly, other treatments like cetuximab target the epidermal growth factor receptor (EGFR) pathway, which is often overactive in colorectal cancer cells, leading to uncontrolled growth. Chemotherapy agents like oxaliplatin and fluorouracil disrupt DNA replication and repair, causing cancer cell death. Understanding these mechanisms is vital for colorectal cancer patients as it helps in selecting the most effective treatment based on the specific molecular characteristics of their tumors, potentially improving outcomes and reducing resistance to therapy.