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

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.

Study Overview

• Status: Recruiting
• Conditions: Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8; Stage III Hypopharyngeal Carcinoma AJCC v8; Stage III Laryngeal Cancer AJCC v8; Stage III Lip and Oral Cavity Cancer AJCC v8; Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8; Stage IVA Lip and Oral Cavity Cancer AJCC v8; Stage IVA Hypopharyngeal Carcinoma AJCC v8; Stage IVA Laryngeal Cancer AJCC v8; Stage IVA Oropharyngeal (p16-Negative) Carcinoma AJCC v8; Stage IVB Hypopharyngeal Carcinoma AJCC v8; Stage IVB Laryngeal Cancer AJCC v8; Stage IVB Oropharyngeal (p16-Negative) Carcinoma AJCC v8; Head and Neck Carcinoma of Unknown Primary; Locally Advanced Head and Neck Squamous Cell Carcinoma; Locally Advanced Hypopharyngeal Squamous Cell Carcinoma; Locally Advanced Laryngeal Squamous Cell Carcinoma; Locally Advanced Oropharyngeal Squamous Cell Carcinoma; Locally Advanced Oral Cavity Squamous Cell Carcinoma; Stage IVB Lip and Oral Cavity Cancer AJCC v8; Locally Advanced Nasal Cavity Squamous Cell Carcinoma; Locally Advanced Paranasal Sinus Squamous Cell Carcinoma; Locally Advanced Sinonasal Squamous Cell Carcinoma; Maxillary Sinus Squamous Cell Carcinoma; Stage III Sinonasal Cancer AJCC v8; Stage IVA Sinonasal Cancer AJCC v8; Stage IVB Sinonasal Cancer AJCC v8
• Intervention / Treatment: Procedure: Magnetic Resonance Imaging; Drug: Cisplatin; Procedure: Biopsy; Procedure: Biospecimen Collection; Radiation: Radiation Therapy; Drug: Ipatasertib; Procedure: Positron Emission Tomography; Procedure: Computed Tomography

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Suspended
      • University Health Network-Princess Margaret Hospital
• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
      • Contact: Site Public Contact; Phone Number: 312-695-1301; Email: cancer@northwestern.edu
      • Principal Investigator: Laila A. Gharzai
  • Kansas
    • Fairway, Kansas, United States, 66205
      • Recruiting
      • University of Kansas Clinical Research Center
      • Contact: Site Public Contact; Phone Number: 913-588-3671; Email: KUCC_Navigation@kumc.edu
      • Principal Investigator: Christopher Lominska
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • University of Kansas Cancer Center
      • Contact: Site Public Contact; Phone Number: 913-588-3671; Email: KUCC_Navigation@kumc.edu
      • Principal Investigator: Christopher Lominska
    • Westwood, Kansas, United States, 66205
      • Recruiting
      • University of Kansas Hospital-Westwood Cancer Center
      • Contact: Site Public Contact; Phone Number: 913-588-3671; Email: KUCC_Navigation@kumc.edu
      • Principal Investigator: Christopher Lominska
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Recruiting
      • University of Kentucky/Markey Cancer Center
      • Contact: Site Public Contact; Phone Number: 859-257-3379
      • Principal Investigator: Susanne M. Arnold
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland/Greenebaum Cancer Center
      • Contact: Site Public Contact; Phone Number: 800-888-8823
      • Principal Investigator: Ranee Mehra
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Recruiting
      • Rutgers Cancer Institute of New Jersey
      • Principal Investigator: Malcolm D. Mattes
      • Contact: Site Public Contact; Phone Number: 732-235-7356
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Recruiting
      • University of Virginia Cancer Center
      • Principal Investigator: Varinder Kaur
      • Contact: Site Public Contact; Phone Number: 434-243-6303; Email: uvacancertrials@hscmail.mcc.virginia.edu
    • Richmond, Virginia, United States, 23298
      • Recruiting
      • Virginia Commonwealth University/Massey Cancer Center
      • Contact: Site Public Contact; Email: CTOclinops@vcu.edu
      • Principal Investigator: Erin R. Alesi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have pathologically confirmed HNSCC (including tumors of the oropharynx, hypopharynx, larynx, oral cavity, nasal cavity, maxillary and other paranasal sinuses, and unknown primary of the head and neck), with measurable disease as per RECIST 1.1

• Oropharyngeal and unknown primary squamous cell cancers must test for human papilloma virus (HPV), for example by p16 immunohistochemistry (IHC), in situ hybridization (ISH), or polymerase chain reaction (PCR). HPV testing is not required for other HNSCC primary tumor sites

  • For the dose escalation phase only (not the expansion phase), patients with p16-positive tumors are eligible if clinical stage III (cT4 or cN3, M0) according to the American Joint Committee on Cancer (AJCC)/TNM Staging System, 8th edition (Ed.)
  • For both the dose escalation and expansion phases, patients with p16-negative (or not tested) tumors are eligible if clinical stage III-IVB (locally advanced but non-metastatic) according to the AJCC/TNM Staging System, 8th Ed.
• Must be candidate for concurrent, definitive cisplatin and radiation therapy as judged by the treating physician
• Able to swallow tablets at the time of enrollment
• Age >= 18 years. Because no dosing or adverse event data are currently available on the use of ipatasertib in combination with chemoradiation in patients < 18 years of age, children are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Life expectancy of greater than 3 months
• Absolute neutrophil count >= 1500/mcL
• Hemoglobin >= 9 g/dL
• Platelets >= 100,000/mcL
• Serum albumin >= 3 g/dL
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN / 2 x institutional ULN
• Alkaline phosphatase (ALP) =< 2.0 x institutional ULN
• Partial thromboplastin time (PTT) (or activated [a]PTT) and international normalized ratio (INR) =< 1.5 institutional ULN (except for patients receiving anticoagulation therapy)

• Creatinine clearance (CLcr) > 50 mL/min

  • For this calculation, use the Cockroft-Gault formula
• Fasting glucose =< 150 mg/dL (8.3 mmol/L) and (when indicated) glycosylated hemoglobin (HbA1c ) =< 7.5% (58 mmol/mol)
• Human immunodeficiency virus (HIV)-infected patients are eligible if on effective anti-retroviral therapy with undetectable viral load within 6 months
• Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative hepatitis B virus surface antigen [HBsAg] test and a positive hepatitis B core antibody [HBcAb] test, accompanied by a negative HBV deoxyribonucleic acid [DNA] test) are eligible. Patients with chronic HBV infection are eligible if the HBV viral load is undetectable on suppressive therapy, if indicated. Patients undergoing current treatment with anti-viral therapy for HBV are ineligible
• Patients with a history of hepatitis C virus (HCV) infection are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• The effects of ipatasertib on the developing human fetus are unknown. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for at least 28 days after the last dose of ipatasertib and agreement to refrain from donating eggs during this same period. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm during the treatment period and for 28 days after the last dose of ipatasertib
• Ability to understand and the willingness to sign a written informed consent document
• For the expansion cohort only, patients must agree to undergo mandatory on-treatment biopsies, and have tumors amenable to on-treatment biopsies. This is not applicable to the dose escalation cohort where no on-treatment biopsies are obtained

Exclusion Criteria:

• Primary tumor of nasopharynx, salivary, thyroid or parathyroid glands, or skin
• Distant metastases from the current HNSCC
• Prior treatment (e.g., chemotherapy, radiation, or definitive surgery) for the current locally advanced HNSCC is not permitted. Biopsies, including those performed under anesthesia, are not considered surgery. Patients who underwent prior definitive surgery alone for an early stage (T1-2N0) HNSCC which has now recurred with stage III-IVB disease at least 3 months after the initial surgery are eligible
• For patients with a prior history of another malignancy, no prior chemotherapy or radiation may have been administered within 6 weeks prior to study entry. Among patients who received prior radiation to the head and neck or adjacent anatomical site for another malignancy, there may be no overlap with current area to be irradiated
• Current use of any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ipatasertib or other agents used in study
• Treatment with strong inhibitors or inducers of CYP3A4 or P-glycoprotein within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drug. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• Patients with uncontrolled intercurrent illness, including active infection
• Pregnant women are excluded from this study because ipatasertib is an oral AKT inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ipatasertib, breastfeeding should be discontinued if the mother is treated with ipatasertib. These potential risks may also apply to other agents used in this study
• Patients with type I or type II diabetes mellitus requiring insulin at study entry. Patients with non-insulin dependent type II diabetes mellitus are eligible, as are patients who are on a stable dose of oral diabetes medication >= 4 weeks prior to initiation of study treatment. Patients with a history of diabetes mellitus, an abnormal fasting glucose level, or other signs or symptoms indicating diabetes mellitus, must meet the laboratory eligibility criteria for fasting blood glucose and hemoglobin A1c
• History of or active inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis) or active bowel inflammation (e.g., diverticulitis)
• History of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills
• Lung disease: pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, aspergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia)
• 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), or cirrhosis.
• Grade >= 2 uncontrolled or untreated hypercholesterolemia (cholesterol > 300 mg/dL or > 7.75 mmol/L) or hypertriglyceridemia (triglycerides > 300 mg/dL or > 3.42 mmol/L)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation (ipatasertib, cisplatin, radiation therapy); 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.	Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Drug: Cisplatin; Given IV; Other Names: CDDP; Cis-diamminedichloridoplatinum; Cismaplat; Cisplatinum; Neoplatin; Platinol; Abiplatin; Blastolem; Briplatin; Cis-diammine-dichloroplatinum; Cis-diamminedichloro Platinum (II); Cis-diamminedichloroplatinum; Cis-dichloroammine Platinum (II); Cis-platinous Diamine Dichloride; Cis-platinum; Cis-platinum II; Cis-platinum II Diamine Dichloride; Cisplatina; Cisplatyl; Citoplatino; Citosin; Cysplatyna; DDP; Lederplatin; Metaplatin; Peyrone's Chloride; Peyrone's Salt; Placis; Plastistil; Platamine; Platiblastin; Platiblastin-S; Platinex; Platinol- AQ; Platinol-AQ; Platinol-AQ VHA Plus; Platinoxan; Platinum; Platinum Diamminodichloride; Platiran; Platistin; Platosin; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Energy Type; Drug: Ipatasertib; Given PO; Other Names: GDC-0068; RG-7440; Procedure: Positron Emission Tomography; Undergo PET/CT; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Positron emission tomography (procedure); Procedure: Computed Tomography; Undergo CT or PET/CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan
Experimental: Dose Expansion (ipatasertib, cisplatin, radiation therapy); 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.	Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Drug: Cisplatin; Given IV; Other Names: CDDP; Cis-diamminedichloridoplatinum; Cismaplat; Cisplatinum; Neoplatin; Platinol; Abiplatin; Blastolem; Briplatin; Cis-diammine-dichloroplatinum; Cis-diamminedichloro Platinum (II); Cis-diamminedichloroplatinum; Cis-dichloroammine Platinum (II); Cis-platinous Diamine Dichloride; Cis-platinum; Cis-platinum II; Cis-platinum II Diamine Dichloride; Cisplatina; Cisplatyl; Citoplatino; Citosin; Cysplatyna; DDP; Lederplatin; Metaplatin; Peyrone's Chloride; Peyrone's Salt; Placis; Plastistil; Platamine; Platiblastin; Platiblastin-S; Platinex; Platinol- AQ; Platinol-AQ; Platinol-AQ VHA Plus; Platinoxan; Platinum; Platinum Diamminodichloride; Platiran; Platistin; Platosin; Procedure: Biopsy; Undergo tumor biopsy; Other Names: Bx; BIOPSY_TYPE; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Energy Type; Drug: Ipatasertib; Given PO; Other Names: GDC-0068; RG-7440; Procedure: Positron Emission Tomography; Undergo PET/CT; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Positron emission tomography (procedure); Procedure: Computed Tomography; Undergo CT or PET/CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD) and recommended phase 2 dose of ipatasertib in combination with definitive chemo-radiation	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).	At the completion of dose escalation phase, up to 56 days from treatment start date

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration and completion rate of prescribed radiation and chemotherapy	Descriptive statistics will also be used to summarize the duration and completion rate of prescribed radiation and chemotherapy.	Up to 2 years
Pharmacokinetic (PK) profile of ipatasertib in combination with cisplatin	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.	Up to 2 years
Pharmacodynamic effects of ipatasertib	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.	Up to 2 years
Relapse-free 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 IHC.	From start of treatment to the time of cancer recurrence or death, whichever occurs first, assessed up to 2 years
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 IHC.	From the start of treatment that patients are still alive, assessed up to 2 years
Acute and late toxicities	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.	From 90 days after the end of radiation treatment up to 1 year from treatment completion date
Objective response rate	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).	Up to 2 years
Locoregional control	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.	From start of treatment to cancer recurrence at the site of the primary tumor or the regional lymph nodes, assessed up to 2 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Malcolm D Mattes, University Health Network Princess Margaret Cancer Center LAO

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: December 28, 2021
• First Submitted That Met QC Criteria: December 28, 2021
• First Posted (Actual): December 29, 2021

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 23, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Otorhinolaryngologic Neoplasms; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Mouth Diseases; Lip Diseases; Neoplasms, Squamous Cell; Laryngeal Diseases; Head and Neck Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Mouth Neoplasms; Laryngeal Neoplasms; Lip Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Cisplatin; Ipatasertib
• Other Study ID Numbers: NCI-2021-13901 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); UM1CA186644 (U.S. NIH Grant/Contract); 10492 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No