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Squamous Cell Carcinoma of Head and Neck

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Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Otorhinolaryngologic Neoplasms

Laryngeal Diseases

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Respiratory Tract Neoplasms

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Oral Squamous Cell Carcinoma

Oral Cancer

Laryngeal Cancer

Hypopharyngeal Cancer

Lip and Oral Cavity Cancer

Antineoplastic Agents

All Drugs and Chemicals

Cisplatin

Ipatasertib

Protein Kinase Inhibitors

Enzyme Inhibitors

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.

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.

Biopsy

Biospecimen Collection

Computed Tomography

Magnetic Resonance Imaging

Positron Emission Tomography

Radiation Therapy

Site Public Contact

Laila A. Gharzai

Christopher Lominska

Susanne M. Arnold

Ranee Mehra

Malcolm D. Mattes

Varinder Kaur

Erin R. Alesi

Malcolm D Mattes

This phase I/Ib trial tests the safety and best dose of ipatasertib in combination with the usual treatment approach using chemotherapy together with radiation therapy ("chemo-radiation") in patients with head and neck cancer. Ipatasertib is in a class of medications called protein kinase B (AKT) inhibitors. It may stop the growth of tumor cells and may kill them. Cisplatin which is a chemotherapy used in this trial is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Radiation therapy uses high energy to kill tumor cells and shrink tumors. Giving ipatasertib in combination with chemo-radiation may be better than chemo-radiation alone in treating patients with advanced head and neck cancer.

PRIMARY OBJECTIVE:

I. To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of ipatasertib in combination with definitive chemoradiation in locally advanced head and neck squamous cell carcinoma (HNSCC) based on dose-limiting toxicities (DLTs).

SECONDARY OBJECTIVES:

I. To assess acute and late toxicities, based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

II. To assess long-term swallowing function, based on gastric tube dependency at 6 and 12 months that is different from baseline.

III. To determine duration and completion rate of prescribed radiation and chemotherapy.

IV. To determine pharmacokinetic profile of ipatasertib in combination with cisplatin and radiation therapy, based on peak and trough blood levels in patients administered ipatasertib orally.

V. To determine pharmacodynamic effects of ipatasertib at the MTD, based on pAKT, pS6 and pPRAS40 as markers of AKT pathway inhibition, and gamma-H2AX as a marker of radiosensitization.

VI. To observe and record anti-tumor activity (objective response rate) by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, locoregional control, relapse-free survival, and overall survival) of the combination of ipatasertib, cisplatin, and radiation therapy in patients with HNSCC.

VII. To correlate efficacy outcomes with tumor genotype, based on whole exome sequencing of pre-treatment biopsy specimens.

OUTLINE: This is a phase I, dose-escalation study of ipatasertib in combination with fixed-dose cisplatin and radiation therapy followed by a dose-expansion study.

DOSE ESCALATION:

Patients receive ipatasertib orally (PO) once daily (QD) or Monday, Wednesday, and Friday depending on dose level on days 1-28 of each cycle. Patients also receive cisplatin intravenously (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 radiation therapy (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 positron emission tomography (PET)/computed tomography (CT), CT, or magnetic resonance imaging (MRI) during screening, follow-up, and as clinically indicated. Patients undergo blood sample collection on trial.

DOSE EXPANSION:

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.

After completion of study treatment, patients are followed for 30 days and then every 3 months for up to 2 years.

Testing the Addition of Ipatasertib to Usual Chemotherapy and Radiation for Head and Neck Cancer

Phase I/Ib Study of AKT Inhibitor Ipatasertib With Chemoradiation for Locally Advanced Head and Neck Cancer

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

Patients who receive at least 70% of the prescribed course of ipatasertib on radiation days will be evaluable for dose limiting toxicity assessment. After the escalation phase of the trial is completed, the MTD will be selected using the pooled-adjacent-violators algorithm, a type of isotonic regression, as specified in Liu and Yuan (2015).

Will be assessed according to Common Terminology Criteria for Adverse Events version 5.0. Toxicities occurring \> 90 days from the end of radiation will be considered late toxicities. This will include assessment of long-term swallowing function, based on gastric tube dependency at 6 and 12 months as compared to baseline due to the effects of the primary tumor. Descriptive statistics will be used to summarize these toxicities.

Descriptive statistics will also be used to summarize the duration and completion rate of prescribed radiation and chemotherapy.

Assessed based on Response Evaluation Criteria in Solid Tumors, as well as locoregional control, relapse-free survival, and overall survival. Two-sample t-test, Mann-Whitney U test, or log rank test will be used where appropriate to analyze the correlation between efficacy outcomes and pre-treatment genotypic abnormalities in the AKT pathway based on whole exome sequencing and PTEN immunohistochemistry (IHC).

Will be assessed using peak and trough blood levels in patients administered ipatasertib orally during weeks 2 and 3 of study treatment. The combined therapy will be compared to historical PK data for drug alone, in order to assess for a drug-drug interaction.

Based on pAKT, pS6 and PRAS40 as markers of AKT pathway inhibition, and gamma-H2AX as a marker of radiosensitization. Two-sample t-test and Mann-Whitney U test will be used where appropriate to compare values before and after the addition of ipatasertib to chemoradiation.

Two-sample t-test, Mann-Whitney U test, or log rank test will be used where appropriate to analyze the correlation between efficacy outcomes and pre-treatment genotypic abnormalities in the AKT pathway based on whole exome sequencing and PTEN IHC.

National Cancer Institute (NCI)

Nasopharyngeal Carcinoma

Tongue Neoplasms

Nasopharyngeal Neoplasms

Pharyngeal Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Tongue Diseases

Patients undergo radiation therapy QD 5 days a week (Monday through Friday) for the first 18 days and then BID for 15 days in the absence of disease progression or unacceptable toxicity.

Proton Beam Radiation Therapy

Quality-of-Life Assessment

Questionnaire Administration

Clifton D Fuller

This phase I trial studies the side effects of image-guided hyper-fractioned proton therapy in treating patients with head and neck cancer that has spread to nearby tissue or lymph nodes (locally advanced) and cannot be removed by surgery (unresectable). Radiation therapy uses high energy protons to kill tumor cells and shrink tumors. The change in dose radiation frequency and dose investigated in this study may help to better control the tumor and prevent it from coming back or growing. The goal of this study is to test a new radiation schedule that administers more radiation to the tumor tissue using image guided proton therapy for patients that have a high risk of having a tumor recurrence (the tumor comes back after treatment).

PRIMARY OBJECTIVE:

I. To assess the safety \& feasibility of image guided mid-treatment hyper-fractioned dose-escalation with proton therapy and identify the maximum tolerable dose (MTD) for the treatment of locally advanced human papillomavirus (HPV) negative head and neck cancer.

OUTLINE:

Patients undergo radiation therapy once daily (QD) 5 days a week (Monday through Friday) for the first 18 days and then twice daily (BID) for 15 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 8 weeks, 3, 6, 9, and 12 months in the first year after radiation therapy, every 4 months in the second year after radiation therapy, and then every 9 months thereafter.

Image-guided Proton Therapy for the Treatment of Locally Advanced Unresectable Head and Neck Cancer

Proton Image-Guided Radiation Assignment for Therapeutic Escalation Via Selection of Locally Advanced Head and Neck Cancer Patients [PIRATES]

Specifically, Common Terminology Criteria for Adverse Events (CTCAE) version 5 grade 4 mucositis, dermatitis or aspiration that does not resolve to a grade =\< 3 in 3 months, and CTCAE version 5 grade \>= 3 myelopathy, and/or osteonecrosis. Summary statistics, including mean, standard deviation and 95% confidence interval will be used to describe safety data. Toxicity will be tabulated and summarized by grade and type.

Specifically, CTCAE version 5 grade 3 mucositis, dermatitis, aspiration, dysphagia, hearing impaired, xerostomia, weight loss, trismus, hoarseness, oropharyngeal pain. Summary statistics, including mean, standard deviation and 95% confidence interval will be used to describe safety data. Toxicity will be tabulated and summarized by grade and type. Radiation induced side effect (RISE) rate will be summarized by frequency, standard deviation and 95% confidence interval.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Testing the Addition of Ipatasertib to Usual Chemotherapy and Radiation for Head and Neck Cancer	NCT05172245	Clinical Stage ... Head and Neck C... Locally Advance... Locally Advance... Locally Advance... Locally Advance... Locally Advance... Locally Advance... Locally Advance... Locally Advance... Maxillary Sinus... Stage III Hypop... Stage III Laryn... Stage III Lip a... Stage III Oroph... Stage III Sinon... Stage IVA Hypop... Stage IVA Laryn... Stage IVA Lip a... Stage IVA Oroph... Stage IVA Sinon... Stage IVB Hypop... Stage IVB Laryn... Stage IVB Lip a... Stage IVB Oroph... Stage IVB Sinon...	Biopsy Biospecimen Col... Cisplatin Computed Tomogr... Ipatasertib Magnetic Resona... Positron Emissi... Radiation Thera...	18 Years -	National Cancer Institute (NCI)
Image-guided Proton Therapy for the Treatment of Locally Advanced Unresectable Head and Neck Cancer	NCT04870840	Locally Advance... Locally Advance... Locally Advance... Locally Advance... Locally Advance... Locally Advance... Malignant Poste... Stage II Cutane... Stage II Hypoph... Stage II Laryng... Stage II Nasoph... Stage II Oropha... Stage III Cutan... Stage III Hypop... Stage III Laryn... Stage III Nasop... Stage III Oroph... Unresectable He... Unresectable Or...	Proton Beam Rad... Quality-of-Life... Questionnaire A...	18 Years -	M.D. Anderson Cancer Center
Image-guided Proton Therapy for the Treatment of Locally Advanced Unresectable Head and Neck Cancer	NCT04870840	Locally Advance... Locally Advance... Locally Advance... Locally Advance... Locally Advance... Locally Advance... Malignant Poste... Stage II Cutane... Stage II Hypoph... Stage II Laryng... Stage II Nasoph... Stage II Oropha... Stage III Cutan... Stage III Hypop... Stage III Laryn... Stage III Nasop... Stage III Oroph... Unresectable He... Unresectable Or...	Proton Beam Rad... Quality-of-Life... Questionnaire A...	18 Years -	M.D. Anderson Cancer Center
Image-guided Proton Therapy for the Treatment of Locally Advanced Unresectable Head and Neck Cancer	NCT04870840	Locally Advance... Locally Advance... Locally Advance... Locally Advance... Locally Advance... Locally Advance... Malignant Poste... Stage II Cutane... Stage II Hypoph... Stage II Laryng... Stage II Nasoph... Stage II Oropha... Stage III Cutan... Stage III Hypop... Stage III Laryn... Stage III Nasop... Stage III Oroph... Unresectable He... Unresectable Or...	Proton Beam Rad... Quality-of-Life... Questionnaire A...	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for locally advanced oral cavity squamous cell carcinoma