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Cemiplimab, Low-Dose Paclitaxel and Carboplatin for the Treatment of Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck

Primary Purpose

Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Metastatic Head and Neck Squamous Cell Carcinoma, Metastatic Hypopharyngeal Squamous Cell Carcinoma

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Carboplatin

Cemiplimab

Paclitaxel

About this trial

This is an interventional treatment trial for Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Recurrent/metastatic (R/M) SCCHN of the oral cavity, oropharynx, larynx and hypopharynx
No prior systemic therapy for treatment of R/M disease
Patients with squamous cell carcinoma of an unknown primary are eligible provided their tumor tested positive for p-16 and they have previously received treatment for locoregional head and neck cancer
Must be at least four weeks since prior systemic therapy, radiation and/or surgery
At least one measurable lesion as defined by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 on screening computed tomography (CT) or magnetic resonance imaging (MRI)
18 years of age and older
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
White blood cell (WBC) count > 2,500 cells/uL
Absolute neutrophil count (ANC) >1,500 cells/uL
Platelet count >= 100,000 cells/uL
Hemoglobin >= 9 g/dL
Creatinine =< 1.6 mg/dL
Total bilirubin =< 1.6 mg/dL
Serum glutamic oxaloacetic transaminase (SGOT) (aspartate transaminase [AST]), serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x upper limit of normal (ULN)
Potassium >= lower limit of normal (LLN)
Willingness to use medically acceptable contraception throughout the study period and four weeks after the final administration of treatment
For female subjects with reproductive potential: a negative serum pregnancy test at baseline
Ability and willingness to provide written informed consent and to comply with the study visits and assessment schedule

Exclusion Criteria:

Disease amenable to curative local therapy
Nasopharyngeal, salivary gland, lip, or sinonasal carcinoma
Disease that requires corticosteroids or other ongoing immunosuppressive treatment
Previous treatment with mAb-based immunotherapy
Previous treatment with PI3K inhibitors
Known brain metastases, unless stable for at least 21 days prior to registration
Known infection human immunodeficiency virus (HIV), hepatitis B or C
Clinically significant cardiac disease (e.g., congestive heart failure, unstable or uncontrolled angina, myocardial infarction) within the past six months
History of pneumonitis within the past five years
Recipient of live vaccines (including attenuated) within 30 days of study treatment
Female patients who are pregnant or breast-feeding
Any other condition or circumstance that could interfere with adherence to the study's procedures or requirements or otherwise compromise the study's objectives in the opinion of the Principal Investigator

Sites / Locations

Ohio State University Comprehensive Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (cemiplimab, paclitaxel, carboplatin)

Arm Description

Patients will be treated with a combination of cemiplimab 350 mg every three weeks, with weekly combination of paclitaxel 25 mg/m2 and carboplatin AUC 1. Treatment will continue for a total of 24 months or until disease progression or unacceptable toxicity. Weekly chemotherapy will stop after six months of treatment (24 weeks). A ten patient safety run-in phase will be initially performed.

Outcomes

Primary Outcome Measures

Overall response rate (ORR)

ORR defined as the proportion of patients with a documented complete response (CR) + partial response (PR) at week 12 of treatment based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. An ORR of 40% (percent) or higher will be consider a positive result. Simon two-stage optimal design will be used.

Secondary Outcome Measures

Progression-free survival (PFS)

PFS will be calculated based on RECIST criteria.

Overall survival (OS)

Incidence of adverse events

Toxicity will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Full Information

NCT ID

NCT04862650

First Posted

March 26, 2021

Last Updated

May 18, 2022

Sponsor

Marcelo Bonomi

1. Study Identification

Unique Protocol Identification Number

NCT04862650

Brief Title

Cemiplimab, Low-Dose Paclitaxel and Carboplatin for the Treatment of Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck

Official Title

A Phase II Trial of the Efficacy and Safety of the Combination of Cemiplimab and Low-Dose Paclitaxel and Carboplatin in Patients With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Recruiting

Study Start Date

November 30, 2021 (Actual)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Marcelo Bonomi

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This phase II trial studies the effect of cemiplimab in combination with low-dose paclitaxel and carboplatin in treating patients with squamous cell carcinoma of the head and neck that has come back (recurrent) or spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as cemiplimab , may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, like paclitaxel and carboplatin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving cemiplimab in combination with paclitaxel and carboplatin may work better in treating recurrent or metastatic squamous cell carcinoma of the head and neck.

Detailed Description

PRIMARY OBJECTIVE: I. To assess the overall response rate (ORR) at 12 weeks of treatment with the treatment combination cemiplimab, paclitaxel, and carboplatin. SECONDARY OBJECTIVES: I. To assess toxicity/tolerance to the proposed treatment combination (a safety run-in phase of ten patients will be performed initially). II. To assess progression-free survival (PFS) and overall survival (OS) at one and two years. EXPLORATORY OBJECTIVES: I. Prospectively test the ability of our clinical nomogram to predict median OS in squamous cell carcinoma of the head and neck (SCCHN) patients planning to receive first-line cemiplimab in combination with low-dose weekly paclitaxel and carboplatin. II. To assess the PFS and OS of patients with combined positive score (CPS) <1%, >1%, and > 20%. III. Compare the predictive power of our nomogram to that of CPS in the prospective cohort, as well as evaluate the combined correlation of nomogram and CPS to median OS. IV. Perform comprehensive immune analysis including phenotypic analysis of immune cell subsets using high dimensional spectral flow cytometry. T cell functionality and ability to produce cytokines after ex vivo stimulation for all T cells and E6/E7-reactive T cells (P16+ subset patients) and TCR sequencing to determine if clonal T cell populations emerge from the tumor of responding patients in comparison with non-responders. OUTLINE: Patients receive cemiplimab intravenously (IV) over 30 minutes every 3 weeks (Q3W) for up to 104 weeks, and paclitaxel IV over 60 minutes and carboplatin IV over 30 minutes once weekly (QW) for up to 24 weeks. Treatment continuous in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 14 days and then every 12 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Metastatic Head and Neck Squamous Cell Carcinoma, Metastatic Hypopharyngeal Squamous Cell Carcinoma, Metastatic Laryngeal Squamous Cell Carcinoma, Metastatic Oral Cavity Squamous Cell Carcinoma, Metastatic Oropharyngeal Squamous Cell Carcinoma, Pathologic Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, 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, Squamous Cell Carcinoma of Unknown Primary, Stage IV Hypopharyngeal Carcinoma AJCC v8, Stage IV Laryngeal Cancer AJCC v8, Stage IV Lip and Oral Cavity Cancer AJCC v8, Stage IVA Hypopharyngeal Carcinoma AJCC v8, Stage IVA Laryngeal Cancer AJCC v8, Stage IVA Lip and Oral Cavity Cancer AJCC v8, Stage IVB Hypopharyngeal Carcinoma AJCC v8, Stage IVB Laryngeal Cancer AJCC v8, Stage IVB Lip and Oral Cavity Cancer AJCC v8, Stage IVC Hypopharyngeal Carcinoma AJCC v8, Stage IVC Laryngeal Cancer AJCC v8, Stage IVC Lip and Oral Cavity Cancer AJCC v8

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment (cemiplimab, paclitaxel, carboplatin)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Other Intervention Name(s)

Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Intervention Description

Given IV

Intervention Type

Biological

Intervention Name(s)

Cemiplimab

Other Intervention Name(s)

Cemiplimab RWLC, Cemiplimab-rwlc, Libtayo, REGN2810

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Paclitaxel

Other Intervention Name(s)

Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Intervention Description

Given IV

Primary Outcome Measure Information:

Title

Overall response rate (ORR)

Description

Time Frame

12 weeks

Secondary Outcome Measure Information:

Title

Progression-free survival (PFS)

Description

PFS will be calculated based on RECIST criteria.

Time Frame

From the date of enrollment until documented disease progression, assessed up to 2 years

Title

Overall survival (OS)

Time Frame

From the date of patient enrollment into the trial until death, assessed up to 2 years

Title

Incidence of adverse events

Description

Toxicity will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Time Frame

Up to 24 weeks

Other Pre-specified Outcome Measures:

Title

Ability of our clinical nomogram to predict median OS in squamous cell carcinoma of the head and neck patients planning to receive first-line cemiplimab in combination with low-dose weekly paclitaxel and carboplatin

Time Frame

Up to 24 weeks

Title

PFS of patients with combined positive score (CPS) < 1%, > 1%, and > 20%

Time Frame

Up to 2 years

Title

OS of patients with CPS < 1%, > 1%, and > 20%

Time Frame

Up to 2 years

Title

Predictive power of our nomogram to that of CPS in the prospective cohort, as well as evaluate the combined correlation of nomogram and CPS to median OS

Time Frame

Up to 24 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Recurrent/metastatic (R/M) SCCHN of the oral cavity, oropharynx, larynx and hypopharynx No prior systemic therapy for treatment of R/M disease Patients with squamous cell carcinoma of an unknown primary are eligible provided their tumor tested positive for p-16 and they have previously received treatment for locoregional head and neck cancer Must be at least four weeks since prior systemic therapy, radiation and/or surgery At least one measurable lesion as defined by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 on screening computed tomography (CT) or magnetic resonance imaging (MRI) 18 years of age and older Eastern Cooperative Oncology Group (ECOG) performance status 0-1 White blood cell (WBC) count > 2,500 cells/uL Absolute neutrophil count (ANC) >1,500 cells/uL Platelet count >= 100,000 cells/uL Hemoglobin >= 9 g/dL Creatinine =< 1.6 mg/dL Total bilirubin =< 1.6 mg/dL Serum glutamic oxaloacetic transaminase (SGOT) (aspartate transaminase [AST]), serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x upper limit of normal (ULN) Potassium >= lower limit of normal (LLN) Willingness to use medically acceptable contraception throughout the study period and four weeks after the final administration of treatment For female subjects with reproductive potential: a negative serum pregnancy test at baseline Ability and willingness to provide written informed consent and to comply with the study visits and assessment schedule Exclusion Criteria: Disease amenable to curative local therapy Nasopharyngeal, salivary gland, lip, or sinonasal carcinoma Disease that requires corticosteroids or other ongoing immunosuppressive treatment Previous treatment with mAb-based immunotherapy Previous treatment with PI3K inhibitors Known brain metastases, unless stable for at least 21 days prior to registration Known infection human immunodeficiency virus (HIV), hepatitis B or C Clinically significant cardiac disease (e.g., congestive heart failure, unstable or uncontrolled angina, myocardial infarction) within the past six months History of pneumonitis within the past five years Recipient of live vaccines (including attenuated) within 30 days of study treatment Female patients who are pregnant or breast-feeding Any other condition or circumstance that could interfere with adherence to the study's procedures or requirements or otherwise compromise the study's objectives in the opinion of the Principal Investigator

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

The Ohio State University Comprehensive Cancer Center

Phone

800-293-5066

OSUCCCClinicaltrials@osumc.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Marcelo R Bonomi, MD

Organizational Affiliation

Ohio State University Comprehensive Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Ohio State University Comprehensive Cancer Center

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43210

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Marcelo R. Bonomi, MD

Marcelo.Bonomi@osumc.edu

First Name & Middle Initial & Last Name & Degree

Marcelo R. Bonomi, MD

12. IPD Sharing Statement

Plan to Share IPD

Links:

URL

http://cancer.osu.edu

Description

The Jamesline

Learn more about this trial

Cemiplimab, Low-Dose Paclitaxel and Carboplatin for the Treatment of Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck

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