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Head and Neck Squamous Cell CarcinomaPhase 1/2NCT04555837

Alisertib and Pembrolizumab for the Treatment of Patients With Rb-deficient Head and Neck Squamous Cell Cancer

A Phase 1/2 study testing Alisertib and Pembrolizumab in people with Head and Neck Squamous Cell Carcinoma and Malignant Solid Neoplasm, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase I/II trial investigates the best dose and effect of alisertib in combination with pembrolizumab in treating patients with Rb-deficient head and neck squamous cell cancer. Alisertib may help block the growth of cancer.. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Alisertib and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteUnited States
Study dates
15 Sep 2020to 8 Apr 2025
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Histologically or cytological confirmed diagnosis of Rb-deficient HNSCC for which no standard curative therapy is available.
  • Rb deficient HNSCC includes CLIA-certified testing confirming one of the following:
  • HPV positive as determined by any one of the following: p16 immunohistochemistry (IHC), HPV RNA in situ hybridization (ISH), RNAscope (mRNA ISH), DNA ISH, DNA PCR, or qRT PCR.
  • No Rb protein expression in the tumor as determined by IHC.41, 48 3. Progression on prior treatment with an anti-PD-1 antibody or an anti-PD-L1 antibody.
  • Has received at least 2 doses of a PD-1/PD-L1 checkpoint blockade therapy. B. Clinical or radiographical progression has been documented within 12 weeks from the last dose of PD-1/PD-L1 checkpoint blockade therapy.
  • 1. Histologically or cytological confirmed diagnosis of an invasive solid tumor malignancy, for which no standard curative or life prolonging therapy is available.
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  • Male or female patients ≥ 18 years of age.
  • ECOG performance status of ≤ 2 (see section 7.4).
  • Clinical laboratory values as specified below within 22 days before the first dose of study drug
  • Absolute neutrophil count (ANC) > 1500/mm³
  • Platelets > 100,000/mm³
  • Hgb > 9 g/dL. Values must be obtained without need for myeloid growth factor or platelet transfusion support within 14 days, however, erythrocyte growth factor is allowed as per published ASCO guidelines.
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
  • SGOT (AST) and SGPT (ALT)< 2.5 x ULN. AST and/or ALT may be up to 5X ULN if with known liver mets or total 3 x ULN with direct bilirubin ≤ ULN in patients with well-documented Gilbert syndrome.
  • Adequate renal function as defined by calculated creatinine clearance ≥30 ml/min (Cockroft-Gault Formula, see Section 7.5).
  • Measurable disease according to RECIST version 1.1.
  • Voluntary written consent must be given before performance of any study related procedure not part of standard of care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
  • Patients must be able to either swallow alisertib enteric coated tablets, swallow alisertib oral solution formulation, or administer alisertib oral solution formulation via a feeding tube that terminates in the stomach.
  • Willing to provide blood and tissue for correlative research purposes.
  • Female patients who:
  • Are postmenopausal for at least 1 year before the screening visit, OR
  • Are surgically sterile, OR
  • If they are of childbearing potential, agree to practice 1 highly effective method of contraception and 1 additional effective (barrier) method at the same time, from the time of signing the informed consent through 120 days after the last dose of study drug, OR
  • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
  • Male patients, even if surgically sterilized (i.e., status postvasectomy), who:
  • Agree to practice effective barrier contraception during the entire study treatment period and through 120 after the last dose of study drug, OR
  • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)

Who cannot join

  • Radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is considered to be over 25%.
  • Prior allogeneic bone marrow or organ transplantation.
  • Known gastrointestinal (GI) disease or GI procedures that could interfere with the oral absorption or tolerance of alisertib. Examples include, but are not limited to partial gastrectomy, history of small intestine surgery, and celiac disease.
  • Inability to swallow (or use a feeding tube to administer) oral medication or inability or unwillingness to comply with the administration requirements related to alisertib.
  • Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen.
  • Requirement for constant administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes throughout the study. The intermittent use of H2-antagonists and antacids (including carafate) is only allowed within these guidelines:
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  • H2 antagonists until D-1 and after the dosing of alisertib is done
  • Antacid formulations until 2 hours before doing and after 2 hours following dosing.
  • PPI is allowed until D-5 of first alisertib dose. PPIs are prohibited throughout the study
  • Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see Section 7.3), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
  • Female subject who is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative urine or serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
  • Female patient who intend to donate eggs (ova) during the course of this study or 120 days after receiving their last dose of study drug(s).
  • Male patients who intend to donate sperm during the course of this study or 120 days after receiving their last dose of study drug(s).
  • Other severe acute or chronic medical or psychiatric condition, including uncontrolled diabetes, malabsorption, resection of the pancreas or upper small bowel, requirement for pancreatic enzymes, any condition that would modify small bowel absorption of oral medications, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.
  • Diagnosed or treated for another invasive malignancy within 2 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
  • Has received any anti-cancer treatment including investigational agents within 21 days prior to first dose of alisertib.
  • Patients who receive gamma knife radiosurgery for brain metastases or whole brain radiation are eligible if gamma knife radiosurgery was completed > 2 weeks before treatment is started or whole brain radiation was performed > 4 weeks before treatment is started, and are clinically stable (not requiring steroids or anti-epileptic drugs).
  • Known hypersensitivity to any of the excipients of alisertib enteric coated tablets or severe reaction to any human monoclonal antibody.
  • Patients with a prior history of clinically significant metabolic acidosis (exclusion only for patients receiving alisertib oral solution).
  • Major surgery within 28 days prior to first dose of alisertib or persisting side effects that have not improved to NCI-CTCAE grade 1 or better.
  • Patients who are on (or will require) prolonged systemic corticosteroid treatment during the study except for replacement dosing for adrenal insufficiency.
  • Concurrent severe and/or uncontrolled medical conditions that would, in the investigator's judgment, contraindicate patient participation in the clinical study or require concomitant anti-cancer drugs (e.g. active or uncontrolled severe infection, chronic active hepatitis, immuno-compromised, acute or chronic pancreatitis, uncontrolled high blood pressure, interstitial lung disease).
  • Patients with active, known, diagnosed or suspected autoimmune disease. Patients suffering from vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring thyroid hormone replacement therapy, or psoriasis not requiring systemic treatment can be enrolled.
  • Patients diagnosed with active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis or another condition requiring immunosuppressive doses of systemic medication such as systemic corticosteroids or absorbed topical corticosteroids (doses ≥ 10 mg/day prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical corticosteroids, adrenal replacement doses, or < 10 mg daily prednisone or equivalent are permitted.
  • Administration of any live vaccine within 30 days before first dose of study drug.
  • Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus or hepatitis C virus, except for: Patients with HIV who have controlled infection (undetectable viral load and CD4 count above 350 cells/mm3 either spontaneously or on a stable antiviral regimen) are permitted; Patients with hepatitis B (HepBsAg+) virus who have controlled infection (serum hepatitis B virus DNA PCR that is below the limit of detection AND receiving antiviral therapy for hepatitis B) are permitted; Patients who are hepatitis C virus antibody positive (HCV Ab +) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted.
  • Participating in another therapeutic clinical trial.
  • Prior immune-related adverse events (irAE) as follows:
  • Any life-threatening irAE will not be eligible.
  • Any grade irAE of the following types will not be eligible:
  • i. Nervous system irAE
  • ii. Ocular irAE
  • iii. Cardiovascular irAE
  • iv. Severe Cutaneous Adverse Reactions (SCAR)
  • v. Hematological irAE
  • Any grade endocrine irAE will be eligible if replacement therapy can compensate for the resulting deficit.
  • Grade ≥ 2 irAE of the following will not be eligible:
  • i. Colitis
  • ii. Hepatitis
  • iii. Bullous Dermatoses
  • iv. Pneumonitis
  • v. Musculoskeletal
  • vi. Renal
  • Grade ≥ 3 cutaneous irAE will not be eligible.
  • All irAEs must have resolved to Grade ≤ 1 at least 14 days before the planned first dose.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase I-II, Open Label Study Evaluating the Safety and Efficacy of Alisertib and Pembrolizumab in Patients With Rb-Deficient Head and Neck Squamous Cell Carcinomas

This phase I/II trial investigates the best dose and effect of alisertib in combination with pembrolizumab in treating patients with Rb-deficient head and neck squamous cell cancer. Alisertib may help block the growth of cancer.. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving alisertib in combination with pembrolizumab may help control Rb-deficient head and neck squamous cell cancer. HPV positive head and neck cancers are Rb-deficient.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the recommend phase II dose of the combination of alisertib and pembrolizumab. (Phase I) II. To determine the overall response rate (ORR) and progression free survival (PFS) of patients with recurrent or metastatic Rb-deficient head and neck squamous cell carcinoma (HNSCC) treated with the combination of pembrolizumab and alisertib. (Phase II)

SECONDARY OBJECTIVES:

  1. To evaluate the safety of the combination of pembrolizumab and alisertib in patients with solid tumors.

II. To determine the overall survival in HNSCC patients treated with the combination of pembrolizumab and alisertib.

III. To determine the relationship between pharmacokinetics, pharmacodynamics, baseline immune and tumor biomarkers and clinical responses in patients treated with alisertib and pembrolizumab.

IV. To determine correlations between clinical responses and the effect of the treatment on human papilloma virus (HPV)-reactive T cells in HPV+ cancers.

  1. To determine correlations between clinical responses and tumor infiltrating lymphocyte function and T cell repertoire.

OUTLINE: This is a phase I, dose-escalation study of alisertib in combination with fixed dose pembrolizumab followed by a phase II study.

Patients receive alisertib orally (PO) twice daily (BID) on days 1-7 and pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2-3 months.

Being tested
Alisertib, Pembrolizumab
Keywords
head and neck cancer, HPV, Immunotherapy, squamous cancer
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Head and Neck Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AlisertibDrug

    Also called Aurora A Kinase Inhibitor MLN8237, MLN-8237, MLN8237

    Given PO

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

Study groups in NCT04555837
Study groupRoleWhat they receive
Treatment (alisertib, pembrolizumab)ExperimentalPatients receive alisertib PO BID on days 1-7 and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Alisertib; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I: The Recommended Phase II Dose Determenation. Phase II: Overall Response Rate (ORR) and Progression Free Survival (PFS)

    Phase I: To determine the recommend phase II dose of the combination of alisertib and pembrolizumab

    Measured: Approximately 33 months

  2. Phase II: Overall Response Rate (ORR)

    Phase II: To determine the overall response rate (ORR) of patients with recurrent or metastatic Rb-deficient head and neck squamous cell carcinoma (HNSCC) treated with the combination of pembrolizumab and alisertib.

    Measured: Approximately 33 months

  3. Phase II: Progression Free Survival (PFS)

    Phase II: To determine the progression free survival (PFS) of patients with recurrent or metastatic Rb-deficient head and neck squamous cell carcinoma (HNSCC) treated with the combination of pembrolizumab and alisertib.

    Measured: Approximately 33 months

Secondary outcomes (5)

  1. The Safety of the Combination of Pembrolizumab and Alisertib

    To evaluate the safety of the combination of pembrolizumab and alisertib in patients with solid tumors.

    Measured: Adverse events were monitored until off study due to disease progression, death, unacceptable toxicity, consent withdrawal, or physician's discretion, approximately 33 months.

  2. The Overall Survival in HNSCC Patients

    To determine the overall survival in HNSCC patients treated with the combination of pembrolizumab and alisertib in Phase II only.

    Measured: 28 patients (4 patients were screen failures) enrolled from September 2020 to June 2023, 24 were treated and evaluable for response. Patients were followed for overall survial for approximately 33 months

  3. The Relationship Between Pharmacokinetics, Pharmacodynamics, Baseline Immune and Tumor Biomarkers and Clinical Responses

    To determine the relationship between pharmacokinetics, pharmacodynamics, baseline immune and tumor biomarkers and clinical responses in patients treated with alisertib and pembrolizumab in phase II only.

    Measured: The trial design dictated that if there were no objective responses in thefirst cohort of the phase II study, the trial would close after the first cohort.

  4. Correlations Between Clinical Responses and the Effect of the Treatment on Human Papilloma Virus (HPV)-Reactive T Cells in HPV+ Cancers.

    To determine correlations between clinical responses and the effect of the treatment on human papilloma virus (HPV)-reactive T cells in HPV+ cancers in phase II only.

    Measured: The trial design dictated that if there were no objective responses in the first cohort of the phase II study, the trial would close after the first cohort.

  5. Correlations Between Clinical Responses and Tumor Infiltrating Lymphocyte Function and T Cell Repertoire.

    To determine correlations between clinical responses and tumor infiltrating lymphocyte function and T cell repertoire in phase II only.

    Measured: The trial design dictated that if there were no objective responses in the first cohort of the phase II study, the trial would close after the first cohort.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Sep 2020
  2. Study start15 Sep 2020
  3. Primary completion8 Apr 2025
  4. Study completion8 Apr 2025

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04555837
Sponsor's protocol ID
2020-0210
Other IDs
NCI-2020-05051, 2020-0210
Status last verified
Apr 2025
First submitted
14 Sep 2020
Last updated
20 May 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Alisertib and Pembrolizumab in people with Head and Neck Squamous Cell Carcinoma and Malignant Solid Neoplasm, run by M.D. Anderson Cancer Center at 1 site in United States.

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 45 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: finished, as of the sponsor's last update on 20 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I: The Recommended Phase II Dose Determenation. Phase II: Overall Response Rate (ORR) and Progression Free Survival (PFS) (time frame: Approximately 33 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04555837.

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 20 May 2025.

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