Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8Phase 1NCT05172245
Testing the Addition of Ipatasertib to Usual Chemotherapy and Radiation for Head and Neck Cancer
A Phase 1 study testing Biopsy Procedure, Biospecimen Collection and Cisplatin in people with Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 and Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, run by National Cancer Institute (NCI) at 18 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Head and Neck Carcinoma of Unknown Primary
- What is being tested?
- Biopsy Procedure, Biospecimen Collection and Cisplatin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 18 sitesin 2 countries
- Study dates
- 19 Sep 2022to 1 Jul 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Patients with p16-positive tumors are eligible if M0 and any of one the following: cT4 or cN3 or cT2-3N2 or imaging-detected extranodal extension (iENE) according to the American Joint Committee on Cancer (AJCC)/TNM Staging System, 8th or 9th edition (Ed.)
- 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 or 9th 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
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- 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 >= 3000/mcL
- Hemoglobin >= 10 g/dL
- Platelets >= 150,000/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) > 60 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, there is a mandatory ask of patients to consider undergoing on-treatment biopsies
Who cannot join
- 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
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- 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)
Trial locations and contacts
18 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
18 sites in 2 countries
United States17 sites, 13 recruiting
- Recruiting
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201
Site Public Contact, 800-888-8823
Ranee Mehra
- Active, not recruiting
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
- Suspended
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
- Recruiting
Northwestern University
Chicago, Illinois, 60611
Site Public Contact, 312-695-1301, cancer@northwestern.edu
Laila A. Gharzai
- Recruiting
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219
Site Public Contact, 513-584-7698, cancer@uchealth.com
Jordan Kharofa
- Active, not recruiting
Atrium Health Cabarrus/LCI-Concord
Concord, North Carolina, 28025
- Recruiting
University of Kansas Clinical Research Center
Fairway, Kansas, 66205
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Christopher Lominska
- Recruiting
University of Kansas Cancer Center
Kansas City, Kansas, 66160
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Christopher Lominska
- Active, not recruiting
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
- Recruiting
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
Site Public Contact, 732-235-7356
Malcolm D. Mattes
- Recruiting
Rutgers New Jersey Medical School
Newark, New Jersey, 07101
Site Public Contact, 732-235-7356
Malcolm D. Mattes
- Recruiting
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
Site Public Contact, 804-628-6430, CTOclinops@vcu.edu
Erin R. Alesi
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
Site Public Contact, 800-679-0775, ClinicalTrials@moffitt.org
George Q. Yang
- Recruiting
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461
Site Public Contact, 718-379-6866, eskwak@montefiore.org
Rafi Kabarriti
- Recruiting
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467
Site Public Contact, 718-379-6866, eskwak@montefiore.org
Rafi Kabarriti
- Recruiting
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, 45069
Site Public Contact, 513-584-7698, cancer@uchealth.com
Jordan Kharofa
- Recruiting
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Christopher Lominska
Canada1 site
- Suspended
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
About this study
Official title: Phase 1/1b 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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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.
- 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.
- Conditions
- Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal 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
- Being tested
- Biopsy Procedure, Biospecimen Collection, Cisplatin, Computed Tomography, Ipatasertib
- Medical subject headings
- Oropharyngeal Neoplasms, Hypopharyngeal Neoplasms, Laryngeal Neoplasms, Mouth Neoplasms, Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biopsy ProcedureProcedure or surgery
Also called Biopsy, BIOPSY_TYPE, Bx
Undergo tumor biopsy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood sample collection
CisplatinDrug
Also called Abiplatin, Blastolem, Briplatin, CDDP
Given IV
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT or PET/CT
IpatasertibDrug
Also called GDC 0068, GDC-0068, GDC0068, RG 7440
Given PO
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
Positron Emission TomographyProcedure or surgery
Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)
Undergo PET/CT
Radiation TherapyRadiation
Also called Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate
Undergo radiation therapy
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation (ipatasertib, cisplatin, radiation therapy) | Experimental | 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. Receives: Procedure: Biospecimen Collection; Drug: Cisplatin; Procedure: Computed Tomography; Drug: Ipatasertib; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy |
| Dose Expansion (ipatasertib, cisplatin, radiation therapy) | Experimental | 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. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Cisplatin; Procedure: Computed Tomography; Drug: Ipatasertib; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: At the completion of dose escalation phase, up to 56 days from treatment start date
Secondary outcomes (8)
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.
Measured: From 90 days after the end of radiation treatment up to 1 year from treatment completion date
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.
Measured: Up to 2 years
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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From start of treatment to cancer recurrence at the site of the primary tumor or the regional lymph nodes, assessed 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.
Measured: 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.
Measured: From the start of treatment that patients are still alive, assessed up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2021
- Study start19 Sep 2022
- Primary completion1 Jul 2027 (estimated)
- Study completion1 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8Studies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 46 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Malcolm D Mattes, Principal investigator, University Health Network Princess Margaret Cancer Center LAO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05172245
- Sponsor's protocol ID
- NCI-2021-13901
- Other IDs
- NCI-2021-13901, 032204, 10492, 10492, UM1CA186644
- Status last verified
- Sep 2026
- First submitted
- 28 Dec 2021
- Last updated
- 22 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/1b Study of AKT Inhibitor Ipatasertib With Chemoradiation for Locally Advanced Head and Neck Cancer
- ClinicalTrials.gov ID
- NCT05172245
- Acronym / sponsor ID
- NCI-2021-13901
- Conditions
- Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 46 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 19 Sep 2022 (actual)
- Primary completion
- 1 Jul 2027 (estimated)
- Study completion
- 1 Jul 2027 (estimated)
- First posted
- 29 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVE:
- 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:
- 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.
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation (ipatasertib, cisplatin, radiation therapy) | Experimental | Procedure: Biospecimen Collection, Drug: Cisplatin, Procedure: Computed Tomography, Drug: Ipatasertib, Procedure: Magnetic Resonance Imaging, Procedure: Positron Emission Tomography, Radiation: Radiation TherapyPatients 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. |
| Dose Expansion (ipatasertib, cisplatin, radiation therapy) | Experimental | Procedure: Biopsy Procedure, Procedure: Biospecimen Collection, Drug: Cisplatin, Procedure: Computed Tomography, Drug: Ipatasertib, Procedure: Magnetic Resonance Imaging, Procedure: Positron Emission Tomography, Radiation: Radiation TherapyPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- 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
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biopsy ProcedureAlso: Biopsy, BIOPSY_TYPE, BxUndergo tumor biopsy | Procedure or surgery | Dose Expansion (ipatasertib, cisplatin, radiation therapy) |
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen CollectionUndergo blood sample collection | Procedure or surgery | Dose Escalation (ipatasertib, cisplatin, radiation therapy), Dose Expansion (ipatasertib, cisplatin, radiation therapy) |
| CisplatinAlso: Abiplatin, Blastolem, Briplatin, CDDPGiven IV | Drug | Dose Escalation (ipatasertib, cisplatin, radiation therapy), Dose Expansion (ipatasertib, cisplatin, radiation therapy) |
| Computed TomographyAlso: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial TomographyUndergo CT or PET/CT | Procedure or surgery | Dose Escalation (ipatasertib, cisplatin, radiation therapy), Dose Expansion (ipatasertib, cisplatin, radiation therapy) |
| IpatasertibAlso: GDC 0068, GDC-0068, GDC0068, RG 7440Given PO | Drug | Dose Escalation (ipatasertib, cisplatin, radiation therapy), Dose Expansion (ipatasertib, cisplatin, radiation therapy) |
| Magnetic Resonance ImagingAlso: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging ScanUndergo MRI | Procedure or surgery | Dose Escalation (ipatasertib, cisplatin, radiation therapy), Dose Expansion (ipatasertib, cisplatin, radiation therapy) |
| Positron Emission TomographyAlso: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)Undergo PET/CT | Procedure or surgery | Dose Escalation (ipatasertib, cisplatin, radiation therapy), Dose Expansion (ipatasertib, cisplatin, radiation therapy) |
| Radiation TherapyAlso: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, IrradiateUndergo radiation therapy | Radiation | Dose Escalation (ipatasertib, cisplatin, radiation therapy), Dose Expansion (ipatasertib, cisplatin, radiation therapy) |
Primary outcome
Maximum tolerated dose (MTD) and recommended phase 2 dose of ipatasertib in combination with definitive chemo-radiation
Time frame: At the completion of dose escalation phase, up to 56 days from treatment start date
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).
8 secondary outcomes
Acute and late toxicities
Time frame: From 90 days after the end of radiation treatment up to 1 year from treatment completion date
Duration and completion rate of prescribed radiation and chemotherapy
Time frame: Up to 2 years
Objective response rate
Time frame: Up to 2 years
Pharmacokinetic (PK) profile of ipatasertib in combination with cisplatin
Time frame: Up to 2 years
Pharmacodynamic effects of ipatasertib
Time frame: Up to 2 years
Locoregional control
Time frame: From start of treatment to cancer recurrence at the site of the primary tumor or the regional lymph nodes, assessed up to 2 years
Relapse-free survival
Time frame: From start of treatment to the time of cancer recurrence or death, whichever occurs first, assessed up to 2 years
Overall survival
Time frame: From the start of treatment that patients are still alive, assessed up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2026.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
University of Kansas Clinical Research Center
Fairway, United States
Malcolm D Mattes principal investigator
University Health Network Princess Margaret Cancer Center LAO
18 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Biopsy Procedure, Biospecimen Collection and Cisplatin in people with Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 and Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, run by National Cancer Institute (NCI) at 18 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) and recommended phase 2 dose of ipatasertib in combination with definitive chemo-radiation (time frame: At the completion of dose escalation phase, up to 56 days from treatment start date). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2026.