Testing the Addition of Ipatasertib to Usual Chemotherapy and Radiation for Head and Neck Cancer
Phase 1/1b Study of AKT Inhibitor Ipatasertib With Chemoradiation for Locally Advanced Head and Neck Cancer
4 other identifiers
interventional
46
2 countries
18
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Sep 2022
Longer than P75 for phase_1
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 28, 2021
CompletedFirst Posted
Study publicly available on registry
December 29, 2021
CompletedStudy Start
First participant enrolled
September 19, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 1, 2027
May 18, 2026
April 1, 2026
4.8 years
December 28, 2021
May 15, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
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 Outcomes (8)
Acute and late toxicities
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
Up to 2 years
Objective response rate
Up to 2 years
Pharmacokinetic (PK) profile of ipatasertib in combination with cisplatin
Up to 2 years
Pharmacodynamic effects of ipatasertib
Up to 2 years
- +3 more secondary outcomes
Study Arms (2)
Dose Escalation (ipatasertib, cisplatin, radiation therapy)
EXPERIMENTALPatients 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)
EXPERIMENTALPatients 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.
Interventions
Given IV
Undergo tumor biopsy
Given PO
Undergo MRI
Undergo blood sample collection
Undergo radiation therapy
Undergo CT or PET/CT
Undergo PET/CT
Eligibility Criteria
You may qualify if:
- 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 clinical stage III (cT4 or cN3, M0) according to the American Joint Committee on Cancer (AJCC)/TNM Staging System, 8th 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 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 \>= 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
- +12 more criteria
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (18)
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Kansas Clinical Research Center
Fairway, Kansas, 66205, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
Rutgers New Jersey Medical School
Newark, New Jersey, 07101, United States
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203, United States
Atrium Health Cabarrus/LCI-Concord
Concord, North Carolina, 28025, United States
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219, United States
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, 45069, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Malcolm D Mattes
University Health Network Princess Margaret Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 28, 2021
First Posted
December 29, 2021
Study Start
September 19, 2022
Primary Completion (Estimated)
July 1, 2027
Study Completion (Estimated)
July 1, 2027
Last Updated
May 18, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
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