What side effects are associated with this type of intervention?

Common treatments for Lip and Oral Cavity Cancer, such as chemotherapy, immunotherapy, and targeted therapy, often come with a range of side effects. Chemotherapy can cause nausea, vomiting, hair loss, and myelosuppression. Immunotherapy, including drugs like pembrolizumab, may lead to immune-related adverse events such as skin rash, colitis, and pneumonitis. Targeted therapies, such as those involving AKT inhibitors like Ipatasertib, can result in side effects including diarrhea, hyperglycemia, and skin rash. It is important for patients to discuss these potential side effects with their healthcare provider to manage them effectively.

What prior FDA approvals exist?

FDA-approved treatments for Lip and Oral Cavity Cancer include immunotherapy agents like pembrolizumab, which is a monoclonal antibody that helps the immune system attack cancer cells. Pembrolizumab has shown efficacy in treating recurrent or metastatic squamous cell carcinoma of the head and neck. Additionally, cetuximab, an anti-EGFR monoclonal antibody, has been approved for use in combination with chemotherapy for similar indications. While specific AKT inhibitors like Ipatasertib are still under investigation, these approved therapies highlight the role of targeted and immunotherapy in managing these cancers.

What other types of research exist?

Promising novel alternatives to Ipatasertib for Lip and Oral Cavity Cancer patients include Pembrolizumab (an anti-PD-1 monoclonal antibody) and its combination with Cetuximab (an EGFR inhibitor), as well as other molecularly targeted therapies like Farnesyltransferase inhibitors (e.g., Tipifarnib) for HRAS mutant cancers. These treatments have shown efficacy in clinical trials for recurrent or metastatic head and neck cancers.

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Protein Kinase Inhibitor

Ipatasertib + Immunotherapy for Head and Neck Cancer

Phase 2

Recruiting

Led By Jacob S Thomas

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

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

Must have

Glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2 (using the Cockcroft-Gault formula).

Patients must be able to provide an archival tissue specimen.

Must not have

Type 1 or Type 2 diabetes mellitus requiring insulin at study entry are ineligible.

Known clinically significant history of liver disease consistent with Child Pugh Class B or C, including active viral or other hepatitis (e.g., positive for hepatitis B surface antigen [HbsAg] or hepatitis C virus [HCV] antibody at screening), current drug or alcohol abuse, or cirrhosis.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline up to 1 year after the last patient is enrolled

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing whether adding a new drug, ipatasertib, to an existing treatment, pembrolizumab, can better treat head and neck cancer that has returned or spread. Ipatasertib may help stop cancer growth, and pembrolizumab helps the immune system attack the cancer. The goal is to see if this combination works better than using pembrolizumab alone. Pembrolizumab has been used in combination with chemotherapy for various cancers, including head and neck cancer, and has shown improved overall survival and response rates.

Who is the study for?

This trial is for adults with recurrent or metastatic squamous cell cancer of the head and neck, excluding nasopharynx cancers. Participants must not have had prior systemic therapy in the metastatic setting, should have proper organ function, no uncontrolled illnesses, and agree to use contraception. Those with certain viral infections must be under control. Pregnant or breastfeeding women are excluded.

What is being tested?

The study compares adding Ipatasertib (an AKT inhibitor that may stop tumor growth) to Pembrolizumab (standard immunotherapy) versus using Pembrolizumab alone. The goal is to see if combining these drugs improves outcomes better than just the standard treatment.

What are the potential side effects?

Potential side effects include reactions related to immune system activation such as inflammation in various organs, infusion-related reactions, fatigue, liver issues due to Ipatasertib's action on proteins within cells, and possibly increased cholesterol or blood sugar levels.

Eligibility Criteria

Inclusion Criteria

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

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My kidney function, measured by GFR, is normal or above 60.

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I can provide a sample of my previously collected tumor tissue.

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My tumor has a PD-L1 score of 1 or higher.

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I am 18 years old or older.

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I am fully active or have some restrictions but can still care for myself.

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My oropharyngeal cancer is tested for HPV status.

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I had hepatitis C but am cured, or I'm being treated with no detectable virus.

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I have a tumor that can be measured with imaging or physical exam.

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My cancer originates in the mouth, throat, or voice box, but not in the upper part of the throat behind the nose.

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My hepatitis B virus is under control with treatment.

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My head or neck cancer has returned or spread and cannot be cured.

Exclusion Criteria

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

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I do not have diabetes that requires insulin.

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I have a significant liver condition, such as hepatitis or cirrhosis.

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My cholesterol and triglyceride levels are under control.

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I do not have conditions that affect my body's ability to absorb nutrients or prevent me from swallowing pills.

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I do not have any uncontrolled illnesses or a history of pneumonitis treated with steroids.

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I do not have lung conditions like pneumonitis or cystic fibrosis.

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I haven't had chemotherapy or radiotherapy in the last 4 to 6 weeks.

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I have or have had inflammatory bowel disease or active bowel inflammation.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from date of randomization until disease progression, death, or date of last contact, whichever occurs first, assessed up to 1 year after the last patient is enrolled

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from date of randomization until disease progression, death, or date of last contact, whichever occurs first, assessed up to 1 year after the last patient is enrolled

This trial's timeline: 3 weeks for screening, Varies for treatment, and from date of randomization until disease progression, death, or date of last contact, whichever occurs first, assessed up to 1 year after the last patient is enrolled for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Progression free survival (PFS)

Secondary study objectives

Changes in Akt, ERK, and MEK signaling

Changes in immune-cell population in peripheral blood

Changes in the tumor microenvironment by immunophenotyping

+3 more

Side effects data

From 2024 Phase 3 trial • 804 Patients • NCT03040999

64%

Radiation skin injury

63%

Stomatitis

58%

Anaemia

56%

Nausea

48%

Dry mouth

45%

Constipation

45%

Weight decreased

44%

Dysphagia

42%

Neutrophil count decreased

33%

Dysgeusia

33%

Vomiting

32%

Fatigue

31%

White blood cell count decreased

28%

Hypomagnesaemia

26%

Decreased appetite

25%

Hypothyroidism

25%

Hypokalaemia

24%

Lymphocyte count decreased

24%

Platelet count decreased

23%

Oropharyngeal pain

23%

Blood creatinine increased

22%

Diarrhoea

22%

Odynophagia

20%

Hypoacusis

20%

Alanine aminotransferase increased

20%

Hyponatraemia

19%

Tinnitus

19%

Oral candidiasis

19%

Asthenia

16%

Pyrexia

16%

Cough

15%

Aspartate aminotransferase increased

15%

Rash

14%

Insomnia

13%

Acute kidney injury

13%

Pharyngeal inflammation

13%

Pruritus

12%

Dysphonia

12%

Gamma-glutamyltransferase increased

11%

Pneumonia

11%

Dehydration

10%

Hyperthyroidism

10%

Hypoalbuminaemia

10%

Hypocalcaemia

10%

Headache

10%

Productive cough

Neck pain

Peripheral sensory neuropathy

Gastrooesophageal reflux disease

Hiccups

Hyperglycaemia

Hyperuricaemia

Dizziness

Hypophosphataemia

Urinary tract infection

Ear pain

Localised oedema

Hyperkalaemia

Erythema

Oral pain

Abdominal pain upper

Arthralgia

Anxiety

Febrile neutropenia

Dyspepsia

Saliva altered

Back pain

Oedema peripheral

Hypertension

Dyspnoea

Nasopharyngitis

Alopecia

Dry skin

Sepsis

Pneumonia aspiration

Trismus

Pneumonitis

Laryngeal oedema

Malnutrition

Pharyngeal haemorrhage

Cellulitis

Septic shock

Systemic infection

Clostridium difficile colitis

Cardiac arrest

Death

Bronchitis

Hepatitis

Immune-mediated hepatitis

Oesophagitis

General physical health deterioration

Hypophagia

Tumour haemorrhage

Cerebrovascular accident

Syncope

Acute respiratory failure

Aspiration

Colitis

Mouth haemorrhage

Hypersensitivity

Acute myocardial infarction

Abscess neck

Device related infection

Stoma site infection

Vascular device infection

Wound infection

Hypercalcaemia

Pulmonary embolism

Respiratory failure

100%

80%

60%

40%

20%

Study treatment Arm

Placebo + CRT Followed by Placebo

Pembrolizumab + CRT Followed by Pembrolizumab

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

Active Control

Group I: Arm I (ipatasertib, pembrolizumab)Experimental Treatment5 Interventions

Patients receive pembrolizumab IV over 30 minutes on day 1 and ipatasertib PO QD on days 1-14 of each cycle. Cycles repeat every 21 days for a period of 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy on study, undergo collection of blood samples on study and during follow up, and undergo CT scans throughout the trial.

Group II: Arm II (pembrolizumab)Active Control4 Interventions

Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for a period of 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy on study, undergo collection of blood samples on study and during follow up, and undergo CT scans throughout the trial.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biopsy

2014

Completed Phase 4

~1150

Biospecimen Collection

2004

Completed Phase 3

~2030

Computed Tomography

2017

Completed Phase 2

~2790

Ipatasertib

2017

Completed Phase 3

~3630

Pembrolizumab

2017

Completed Phase 3

~3130

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 Lip and Oral Cavity Cancer include surgery, radiation therapy, and chemotherapy. Surgery involves the physical removal of the tumor, which is crucial for localized control of the disease. Radiation therapy uses high-energy rays to kill cancer cells and shrink tumors, often used post-surgery to eliminate residual cancer cells. Chemotherapy involves drugs that target rapidly dividing cells, including cancer cells, to inhibit their growth and induce cell death. Targeted therapies, such as Protein Kinase B (AKT) inhibitors like Ipatasertib, work by blocking specific pathways that cancer cells use to grow and survive. This is particularly important for Lip and Oral Cavity Cancer patients as these targeted treatments can potentially offer more effective and less toxic options compared to traditional chemotherapy, improving outcomes and quality of life.