What side effects are associated with this type of intervention?

Common treatments for Head and Neck Cancers, including chemotherapy, radiation therapy, and targeted therapies like cetuximab, often result in side effects such as nausea, fatigue, rash, leukopenia, and thrombocytopenia. Severe adverse events can include hypomagnesemia, severe skin reactions, and sepsis. Combination treatments, while potentially more effective, can lead to increased but generally manageable toxicity. Specific to AKT inhibitors like Ipatasertib, side effects may include those typical of targeted therapies, such as rash and fatigue.

What prior FDA approvals exist?

FDA-approved treatments for head and neck cancers include cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), which has shown efficacy when combined with chemotherapy. Pembrolizumab, an immune checkpoint inhibitor targeting PD-1, is approved for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with PD-L1 expression. While ipatasertib, an AKT inhibitor, is still under investigation, these approved treatments highlight the focus on targeted therapies and immunotherapies in managing head and neck cancers.

What other types of research exist?

Promising novel alternatives to Ipatasertib for head and neck cancer patients include: 1) Afatinib and Pembrolizumab combination, which showed efficacy in the ALPHA study for platinum-refractory, recurrent, or metastatic HNSCC. 2) Palbociclib, a CDK4/6 inhibitor, in combination with Cetuximab, which demonstrated safety and tumor responses in recurrent/metastatic HNSCC. 3) Combination of Ponatinib and PLX4720, which exhibited significant synergistic anticancer activity in preclinical models of BRAF V600E thyroid cancer and could be considered for similar mutations in head and neck cancers.

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Platinum-containing Compound

Ipatasertib + Chemoradiation for Head and Neck Cancer

Phase 1

Recruiting

Led By Malcolm D Mattes

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

Able to swallow tablets at the time of enrollment

Age >= 18 years

Must not have

Primary tumor of nasopharynx, salivary, thyroid or parathyroid glands, or skin

Patients with uncontrolled intercurrent illness, including active infection

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests the safety and best dose of ipatasertib combined with chemo-radiation in patients with advanced head and neck cancer. Ipatasertib may help stop or kill cancer cells by blocking a protein they need to grow. The goal is to see if this combination works better than chemo-radiation alone.

Who is the study for?

Adults with advanced head and neck cancer who can swallow tablets, have no prior treatment for their current cancer, and meet certain health criteria. They must not be pregnant or breastfeeding, have serious liver disease, uncontrolled illnesses like infections or diabetes requiring insulin, nor a history of allergic reactions to similar drugs.

What is being tested?

The trial is testing the safety and optimal dose of Ipatasertib when added to standard chemo-radiation therapy in treating head and neck cancers. It compares the effects of this combination against usual treatments alone to see if it's more effective in stopping tumor growth.

What are the potential side effects?

Ipatasertib may cause side effects such as high blood sugar levels, diarrhea, rash, fatigue, and nausea. Cisplatin can lead to kidney problems, hearing loss, nerve damage while radiation therapy might result in skin irritation at the treated site.

Eligibility Criteria

Inclusion Criteria

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

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I can swallow pills.

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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 head or neck cancer is confirmed and can be measured.

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I am eligible for treatment with cisplatin and radiation at the same time.

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My throat cancer has been tested for HPV.

Exclusion Criteria

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

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My cancer originates from the nasopharynx, salivary, thyroid, parathyroid glands, or skin.

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I do not have any uncontrolled illnesses or active infections.

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I have a condition that affects how my body absorbs food.

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

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I have not received any treatment for my advanced head and neck cancer.

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My head or neck cancer has spread to distant parts of my body.

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I have Type I diabetes and need insulin.

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I have high cholesterol or triglycerides that are not under control.

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I have a serious liver condition.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 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

Maximum tolerated dose (MTD) and recommended phase 2 dose of ipatasertib in combination with definitive chemo-radiation

Secondary study objectives

Acute and late toxicities

Duration and completion rate of prescribed radiation and chemotherapy

Locoregional control

+5 more

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: Dose Expansion (ipatasertib, cisplatin, radiation therapy)Experimental Treatment8 Interventions

Patients receive ipatasertib PO MTD on days 2-28 or 3-28 of cycle 1 and 1-28 of subsequent cycles. Patients also receive cisplatin IV weekly on day 1 of cycle 1, weeks 1-4 and day 1 of cycle 2, weeks 1-3 for 7 doses. Patients undergo RT daily (Monday-Friday) for 35 fractions during weeks 1-7. Treatment repeats every 28 days for a total of 2 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT, CT, or MRI during screening, follow-up, and as clinically indicated. Patients undergo blood sample collection and tumor biopsy on trial.

Group II: Dose Escalation (ipatasertib, cisplatin, radiation therapy)Experimental Treatment7 Interventions

Patients receive ipatasertib PO QD or Monday, Wednesday, and Friday depending on dose level on days 1-28 of each cycle. Patients also receive cisplatin IV weekly on day 1 of cycle 1, weeks 1-4 and day 1 of cycle 2, weeks 1-3 for 7 doses. Patients undergo RT daily (Monday-Friday) for 35 fractions during weeks 1-7. Treatment repeats every 28 days for a total of 2 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT, CT, or MRI during screening, follow-up, and as clinically indicated. Patients undergo blood sample collection on trial.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biospecimen Collection

2004

Completed Phase 3

~2030

Biopsy

2014

Completed Phase 4

~1150

Cisplatin

2013

Completed Phase 3

~3120

Computed Tomography

2017

Completed Phase 2

~2790

Ipatasertib

2017

Completed Phase 3

~3630

Magnetic Resonance Imaging

2017

Completed Phase 3

~1180

Positron Emission Tomography

2011

Completed Phase 2

~2200

Radiation Therapy

2017

Completed Phase 3

~7250

0 / 15Eligibility 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

The most common treatments for Head and Neck Cancers include radiation therapy, chemotherapy, and targeted therapies. Radiation therapy uses high-energy rays to kill cancer cells by damaging their DNA. Chemotherapy, such as cisplatin, works by interfering with the DNA replication process, leading to cell death. Targeted therapies, including EGFR inhibitors and AKT inhibitors like Ipatasertib, focus on specific molecular pathways that are crucial for cancer cell survival and proliferation. EGFR inhibitors block the epidermal growth factor receptor, which is often overexpressed in these cancers, while AKT inhibitors disrupt the PI3K/Akt pathway, which is involved in cell growth and survival. These treatments are significant for patients as they offer more precise and potentially effective options, especially for those with advanced or resistant forms of Head and Neck Cancers.

Recent insights in the PI3K/Akt pathway as a promising therapeutic target in combination with EGFR-targeting agents to treat head and neck squamous cell carcinoma.Is biomarker research advancing in the era of personalized medicine for head and neck cancer?Proteomic signatures of epidermal growth factor receptor and survival signal pathways correspond to gefitinib sensitivity in head and neck cancer.