Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    ea3191
Previous Study | Return to List | Next Study

Testing What Happens When an Immunotherapy Drug (Pembrolizumab) is Added to Radiation or Given by Itself Compared to the Usual Treatment of Chemotherapy With Radiation After Surgery for Recurrent Head and Neck Squamous Cell Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04671667
Recruitment Status : Recruiting
First Posted : December 17, 2020
Last Update Posted : September 21, 2021
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase II trial studies the effect of pembrolizumab in combination with radiation therapy or pembrolizumab alone compared to the usual approach (chemotherapy plus radiation therapy) after surgery in treating patients with head and neck squamous cell carcinoma that has come back (recurrent) or patients with a second head and neck cancer that is not from metastasis (primary). Radiation therapy uses high energy radiation or protons to kill tumor cells and shrink tumors. Chemotherapy drugs, such as cisplatin and carboplatin kill tumor cells by stopping them from dividing. 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 pembrolizumab in combination with radiation therapy or pembrolizumab alone after surgery may work better than the usual approach in shrinking recurrent or primary head and neck squamous cell carcinoma.

Condition or disease Intervention/treatment Phase
Recurrent Head and Neck Squamous Cell Carcinoma Recurrent Hypopharyngeal Squamous Cell Carcinoma Recurrent Laryngeal Squamous Cell Carcinoma Recurrent Oral Cavity Squamous Cell Carcinoma Recurrent Oropharyngeal Squamous Cell Carcinoma Drug: Carboplatin Drug: Cisplatin Radiation: Intensity-Modulated Radiation Therapy Biological: Pembrolizumab Radiation: Proton Beam Radiation Therapy Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate overall survival (OS) of adjuvant reirradiation plus concurrent pembrolizumab followed by pembrolizumab to complete 12 months total of pembrolizumab to adjuvant reirradiation plus concurrent platinum chemotherapy in high risk head and neck squamous cell carcinoma (HNSCC) patients.

II. To evaluate OS of adjuvant pembrolizumab for 12 months compared to adjuvant reirradiation plus concurrent platinum chemotherapy in high risk HNSCC patients.

SECONDARY OBJECTIVES:

I. To evaluate the following endpoints in all arms: disease free survival (DFS), locoregional control, rates of distant metastasis, toxicity.

II. To evaluate whether high PD-L1 expression (defined as Combined Positive Score [CPS] >= 20) is predictive of increased efficacy in the experimental groups compared to control.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 6 weeks for 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo intensity modulated radiation therapy (IMRT) or proton beam radiation therapy (PBRT) once daily (QD) for a total of 30 fractions in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive cisplatin or carboplatin IV on day 1. Treatment repeats every 7 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo IMRT or PBRT QD for a total of 30 fractions in the absence of disease progression or unacceptable toxicity.

ARM C: Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 6 weeks for 9 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, and then every 6 months for up to 5 years from the date of registration

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 282 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Randomized Trial of Adjuvant Therapy With Pembrolizumab After Resection of Recurrent/Second Primary Head and Neck Squamous Cell Carcinoma With High Risk Features
Actual Study Start Date : January 8, 2021
Estimated Primary Completion Date : February 28, 2026
Estimated Study Completion Date : February 28, 2026


Arm Intervention/treatment
Experimental: Arm A (pembrolizumab, IMRT, PBRT)
Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 6 weeks for 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo IMRT or PBRT QD for a total of 30 fractions in the absence of disease progression or unacceptable toxicity.
Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
  • Radiation, Intensity-Modulated Radiotherapy

Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475

Radiation: Proton Beam Radiation Therapy
Undergo PBRT
Other Names:
  • PBRT
  • Proton
  • Proton EBRT
  • Proton External Beam Radiotherapy
  • Proton Radiation Therapy
  • Radiation, Proton Beam

Active Comparator: Arm B (cisplatin, carboplatin, IMRT, PBRT)
Patients receive cisplatin or carboplatin IV on day 1. Treatment repeats every 7 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo IMRT or PBRT QD for a total of 30 fractions in the absence of disease progression or unacceptable toxicity.
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carboplatinum
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin

Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
  • Radiation, Intensity-Modulated Radiotherapy

Radiation: Proton Beam Radiation Therapy
Undergo PBRT
Other Names:
  • PBRT
  • Proton
  • Proton EBRT
  • Proton External Beam Radiotherapy
  • Proton Radiation Therapy
  • Radiation, Proton Beam

Experimental: Arm C (pembrolizumab)
Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 6 weeks for 9 cycles in the absence of disease progression or unacceptable toxicity.
Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475




Primary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: From randomization to date of death from any cause, measured at 2 years ]
    Kaplan-Meier estimates will be used to estimate the OS distributions. A log-rank test with one-sided 5% type I error will be used for each of the two primary comparisons.

  2. Incidence of adverse events [ Time Frame: Up to 5 years from date of registration ]
    Assessed using Common Terminology Criteria for Adverse Events. An 80% confidence interval around the hazard ratio of the two experimental arms will be calculated. Toxicity will be compared between the two treatment arms. Toxicity will be examined by arm and compared using the Fisher's exact test.


Secondary Outcome Measures :
  1. Disease free survival [ Time Frame: From the date of randomization to the date of recurrence, second primary tumor from the head and neck region, or death, assessed up to 5 years from date of registration ]
  2. PD-L1 expression [ Time Frame: Up to 5 years from date of registration ]
    Defined as Combined Positive Score >= 20 as a predictive marker of efficacy.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient must be between 18 and 79 years of age
  • Patient must have locoregionally recurrent or second primary HNSCC (oral cavity, oropharynx, larynx, hypopharynx) in a previously radiated field
  • Patient must have undergone surgery with gross total resection and must be randomized within 8 weeks of surgery
  • Patients must have high risk disease defined as:

    • Positive margins and/or extra nodal extension (ENE)

      • Positive margins are defined as malignancy at or within 1 mm of the margin. High grade dysplasia (i.e. carcinoma in situ) at the margin is also considered positive
      • ENE may be either gross or microscopic
  • Patient must have a PD-L1 Combined Positive Score (CPS) >= 1 in a Clinical Laboratory Improvement Act (CLIA) certified laboratory. Testing can be done locally as long as it is done in a CLIA certified laboratory. This testing must be on the tumor specimen from the resection of the patient's recurrent or second primary HNSCC
  • Patient must have had prior radiation to the area of recurrent or second primary tumor. This is defined as > 50% of the presurgical tumor volume having previously received a dose of > 45 Gy as determined by the treating radiation oncologist
  • Patient must have completed prior radiation a minimum of 6 months prior to randomization
  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
  • Patient of childbearing potential and sexually active males must not expect to conceive or father children by using by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse while on study treatment, and continue for 120 days after the last dose of study treatment
  • Patient of childbearing potential must have had a positive urine pregnancy test (within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Absolute neutrophil count (ANC) >= 1,500/mcL (obtained =< 28 days prior to protocol randomization)
  • Platelets >= 100,000/mcL (obtained =< 28 days prior to protocol randomization)
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (obtained =< 28 days prior to protocol randomization)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3.0 x institutional ULN (obtained =< 28 days prior to protocol randomization)
  • Creatinine clearance > 30 ml/min using the Cockcroft-Gault formula (obtained =< 28 days prior to protocol randomization)
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional classification. Patients with New York Heart Association class III or IV heart failure are not eligible
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial as long as they have not been HIV-infected with a history of Kaposi sarcoma and/or multicentric Castleman disease

Exclusion Criteria:

  • Patient must not have any evidence of distant disease based on baseline imaging done within 28 days prior to randomization
  • Patient must not have received anti-PD-1/PD-L1 therapy for recurrent disease. If the patient received anti-PD-1/PD-L1 therapy as part of initial upfront curative intent treatment (either as part of definitive non-surgical therapy or in the adjuvant setting) in the past, the last dosage of anti-PD-1/PD-L1 therapy must have been given greater than one year prior to randomization
  • Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All females of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy. A urine or serum pregnancy test must be repeated within 72 hours prior to receiving the first dose of pembrolizumab or chemotherapy if the test done for eligibility/randomization is done outside of this 72 hour window. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Patient must not have a current active infection that requires systemic treatment at time of randomization
  • Patient must not have a history of non-infectious pneumonitis requiring steroids within 3 years prior to randomization
  • Patient must not have a history of solid organ transplant or stem cell transplant
  • Patient must not be on immunosuppressive medication within 7 days prior to randomization, EXCEPT for the following: a) intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b) systemic corticosteroids at physiologic doses =< 10 mg/day of prednisone or equivalent; c) steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication)
  • Patient must not have received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
  • Patient must not have severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients
  • Patient must not have an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
  • Patient must not have a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
  • Patient must not have a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid [RNA] [qualitative] is detected) infection

    • NOTE: No testing for hepatitis B and hepatitis C is required unless mandated by a local health authority

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04671667


Locations
Show Show 67 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Dan P Zandberg ECOG-ACRIN Cancer Research Group
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT04671667    
Other Study ID Numbers: NCI-2020-13174
NCI-2020-13174 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
EA3191 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
EA3191 ( Other Identifier: CTEP )
U10CA180820 ( U.S. NIH Grant/Contract )
First Posted: December 17, 2020    Key Record Dates
Last Update Posted: September 21, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
URL: https://grants.nih.gov/policy/sharing.htm

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Cisplatin
Carboplatin
Pembrolizumab
Antineoplastic Agents
Antineoplastic Agents, Immunological