Testing the Addition of an Anti-cancer Drug, Ipatasertib, to the Usual Immunotherapy Treatment (Pembrolizumab) in Patients With Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck
A Phase 2 Study of Ipatasertib in Combination With Pembrolizumab for First Line Treatment of Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck
4 other identifiers
interventional
52
1 country
20
Brief Summary
This phase II trial compares the effect of adding ipatasertib to pembrolizumab (standard immunotherapy) vs. pembrolizumab alone in treating patients with squamous cell cancer of the head and neck that has come back (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). 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. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving ipatasertib in combination with pembrolizumab may be more effective than pembrolizumab alone in improving some outcomes in patients with recurrent/metastatic squamous cell cancer of the head and neck.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jul 2022
Longer than P75 for phase_2
20 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
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
July 26, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2027
April 13, 2026
March 1, 2026
4.9 years
December 28, 2021
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Progression free survival (PFS)
The 1-sided log rank test for equality of risk for PFS-event will be performed (Dang et al., 2020). If the p-value is less than or equal to 0.15, it will be concluded that the ipatasertib plus pembrolizumab has sufficient efficacy for further evaluation.
From date of randomization until disease progression, death, or date of last contact, whichever occurs first, assessed up to 1 year after the last patient is enrolled
Secondary Outcomes (6)
Incidence of adverse events
Up to 1 year after the last patient is enrolled
Overall response rate
Up to 1 year after the last patient is enrolled
Duration of response
From the date of the scan that first documented a PR or CR until the patient demonstrates a PFS event, assessed up to 1 year after the last patient is enrolled
Changes in the tumor microenvironment by immunophenotyping
Baseline up to 1 year after the last patient is enrolled
Changes in Akt, ERK, and MEK signaling
Baseline up to 1 year after the last patient is enrolled
- +1 more secondary outcomes
Study Arms (2)
Arm I (ipatasertib, pembrolizumab)
EXPERIMENTALPatients receive pembrolizumab IV over 30 minutes on day 1 and ipatasertib PO QD on days 1-14 of each cycle. Cycles repeat every 21 days for a period of 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy on study, undergo collection of blood samples on study and during follow up, and undergo CT scans throughout the trial.
Arm II (pembrolizumab)
ACTIVE COMPARATORPatients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for a period of 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy on study, undergo collection of blood samples on study and during follow up, and undergo CT scans throughout the trial.
Interventions
Undergo biopsy
Undergo collection of blood samples
Undergo CT
Given PO
Given IV
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed recurrent or metastatic HNSCC that is considered incurable.
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm (\>= 2 cm) by chest x-ray or as \>=10 mm (\>= 1 cm) with CT scan, magnetic resonance imaging (MRI), or calipers by clinical exam.
- Primary tumor locations of oral cavity, oropharynx, hypopharynx, and larynx are allowed. Participants may not have a primary tumor site of nasopharynx.
- Patients with oropharyngeal cancer must have known human papillomavirus (HPV) status defined by human papillomavirus type 16 (p16) testing.
- Patients should not have had prior systemic therapy administered in the recurrent or metastatic setting. Systemic therapy which was given as part of multimodal treatment for locally advanced disease is allowed.
- Patients must be able to provide an archival tissue specimen.
- Patients must be willing to undergo a mandatory tumor biopsy on treatment
- Tumor tissue must have a documented combined positive score (CPS) of \>= 1 for PD-L1.
- Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of ipatasertib in combination with pembrolizumab in patients \< 18 years of age, children are excluded from this study.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Karnofsky \>= 60%).
- Absolute neutrophil count \>= 1,000/mcL.
- Platelets \>= 100,000/mcL.
- 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 \[SGPT\]) =\< 3 x institutional ULN.
- Creatinine =\< 1.5 x institutional ULN.
- +11 more criteria
You may not qualify if:
- Prior treatment with a checkpoint inhibitor given for relapsed or metastatic disease. Prior treatment with a checkpoint inhibitor for locally advanced disease as part multidisciplinary treatment is allowed.
- History of malabsorption syndrome or other condition that would interfere with enteral absorption or result in the inability or unwillingness to swallow pills.
- Patient has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the study principal investigator (PI).
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine or physiologic corticosteroid replacement for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Type 1 or Type 2 diabetes mellitus requiring insulin at study entry are ineligible.
- Patients who are on a stable dose of oral diabetes medication \>= 4 weeks prior to initiation of study treatment may be eligible for enrollment. Patients must meet the laboratory eligibility criteria for fasting blood glucose and hemoglobin A1c.
- Fasting glucose =\< 150 mg/dL (8.3 mmol/L) and hemoglobin A1c =\< 7.5% (58 mmol/mol).
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1). Note: Patients with grade =\< 2 neuropathy or grade =\< 2 alopecia are an exception to this criterion and may qualify for the study. Note: If patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- Patients who are receiving any other investigational agents.
- Patients with known active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ipatasertib or hypersensitivity (grade \>= 3) to pembrolizumab and/or any of the components of the solution for injection.
- Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drug is prohibited. 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 but not limited to interstitial lung disease or active, non-infectious pneumonitis) or a history of (non-infectious) pneumonitis that required steroids.
- Patients with psychiatric illness/social situations that would limit compliance with study requirements.
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (20)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
City of Hope at Irvine Lennar
Irvine, California, 92618, United States
City of Hope Antelope Valley
Lancaster, California, 93534, United States
Keck Medicine of USC Koreatown
Los Angeles, California, 90020, United States
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
USC Norris Oncology/Hematology-Newport Beach
Newport Beach, California, 92663, United States
Stanford Cancer Institute Palo Alto
Palo Alto, California, 94304, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
NYU Langone Hospital - Long Island
Mineola, New York, 11501, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
NYP/Weill Cornell Medical Center
New York, New York, 10065, 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
University of Texas Medical Branch
Galveston, Texas, 77555-0565, United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jacob S Thomas
City of Hope Comprehensive Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 28, 2021
First Posted
December 29, 2021
Study Start
July 26, 2022
Primary Completion (Estimated)
June 30, 2027
Study Completion (Estimated)
June 30, 2027
Last Updated
April 13, 2026
Record last verified: 2026-03
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