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Avelumab With or Without Cetuximab in Treating Patients With Advanced Skin Squamous Cell Cancer

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ClinicalTrials.gov Identifier: NCT03944941
Recruitment Status : Recruiting
First Posted : May 10, 2019
Last Update Posted : June 5, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Brief Summary:
This phase II trial studies how well avelumab with or without cetuximab work in treating patients with skin squamous cell cancer that has spread to other places in the body. Immunotherapy with monoclonal antibodies, such as avelumab and cetuximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Condition or disease Intervention/treatment Phase
Skin Squamous Cell Carcinoma Metastatic Skin Cancer Drug: Avelumab Drug: Cetuximab Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate whether treatment with avelumab plus cetuximab prolongs progression free survival (PFS) compared to avelumab alone.

SECONDARY OBJECTIVES:

I. To evaluate the confirmed objective response rate of each treatment arm. II. To evaluate the clinical benefit rate of each treatment arm. III. To evaluate the PFS of cetuximab plus avelumab in patients that have progressed on single agent avelumab.

IV. To evaluate the overall survival (OS) for each treatment arm. V. To evaluate toxicity across treatment arms of avelumab plus cetuximab and avelumab alone.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive avelumab intravenously (IV) over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients with avelumab failure will crossover to arm II.

ARM II: Patients receive cetuximab IV over 1-2 hours on days 1, 8,15, and 22 and avelumab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 cycles for cetuximab and 24 cycles for avelumab in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months until disease progression, then every 6 months for up to 2 years.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 59 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Randomized Trial of Avelumab Plus Cetuximab Versus Avelumab Alone in Advanced Cutaneous Squamous Cell Carcinoma of the Skin (cSCC)
Actual Study Start Date : May 17, 2019
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Arm I (Avelumab)
Patients receive avelumab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients with avelumab failure will crossover to Arm II.
Drug: Avelumab
Given IV

Experimental: Arm II (Avelumab, cetuximab)
Patients receive cetuximab IV over 1-2 hours on days 1, 8,15, and 22 and avelumab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 cycles for cetuximab and 24 cycles for avelumab in the absence of disease progression or unacceptable toxicity.
Drug: Avelumab
Given IV

Drug: Cetuximab
Given IV




Primary Outcome Measures :
  1. Prolonging of progression free survival (PFS) on avelumab and cetuximab compared to avelumab alone [ Time Frame: Time between registration and evidence of disease progression or death, assessed up to 2 years post treatment ]
    The study will be declared promising if, after the 37th PFS event, the hazard ratio is less than 0.758.


Secondary Outcome Measures :
  1. Confirmed objective response rate (RR) [ Time Frame: Up to 2 years post treatment ]
    A patient will be declared a success for RR if they achieve a partial response (PR) or better on two consecutive evaluations (at least 8 weeks apart). The number of successes will be divided by the number of evaluable patients to estimate the RR for each treatment arm and exact 95% confidence intervals will be calculated based on the properties of the binomial distribution.

  2. Clinical benefit rate (CBR) [ Time Frame: Up to 2 years post treatment ]
    The CBR is will be estimated as the number of successes divided by the total number of evaluable patients. An exact 95% confidence interval will be constructed around the CBR using the properties of the binomial distribution.

  3. PFS in patients who have progressed on avelumab alone [ Time Frame: From time of enrollment to documented progression (or death), assessed up to 2 years ]
    Will explore the PFS for those patients that crossover to combination therapy (avelumab + cetuximab) after progressing on avelumab alone (baseline time being the time of crossover). The Kaplan-Meier method will be used to calculate a median PFS as well as a 95% confidence interval.

  4. Overall Survival (OS) [ Time Frame: Time between enrollment and or death, assessed up to 2 years post treatment ]
    The Kaplan-Meier method will be used to calculate a median OS as well as a 95% confidence interval.

  5. Incidence of adverse events [ Time Frame: Up to 30 days post treatment ]
    Will be described and graded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Maximum grade adverse events will be summarized in a tabular setting by treatment arm.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • PRE-REGISTRATION ELIGIBILITY CRITERIA
  • Provide adequate tissue for PD-L1 testing

    * Fresh tissue or archival tissue can be used. Sample must be at least core needle biopsy. Fine needle aspiration is not adequate. This specimen submission is mandatory prior to registration as results will be used for stratification

  • REGISTRATION ELIGIBILITY CRITERIA
  • Biopsy-proven advanced cutaneous squamous cell carcinoma. Advanced disease is defined as either metastatic cutaneous squamous cell carcinoma or locally advanced cutaneous squamous cell carcinoma not amenable to curative surgical resection, or the patient declines surgical resection
  • The patient must have at least one lesion that is measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Patients who received prior treatment with cetuximab as palliative treatment for advanced cutaneous squamous cell carcinoma (cSCC) are excluded. Patients that received cetuximab based chemoradiation as prior treatment for locally advanced disease are eligible as long as the last dosage was given >= 6 months prior to registration
  • Patients who received cetuximab as part of definitive therapy in the adjuvant setting are eligible as long as the last dosage was given >= 6 months prior to registration
  • Patients who received prior cetuximab and had a severe infusion reaction requiring discontinuation of cetuximab are excluded
  • Patients treated with prior anti-PD-1 or anti-PD-L1 monoclonal antibodies (mAbs) are excluded
  • Patients cannot have received treatment with radiation or chemotherapy including another investigational agent within 2 weeks of registration. Other than as stated above for cetuximab there are no limits on the number of lines of other therapies given for advanced cSCC
  • If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • This study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done =< 7 days prior to registration is required
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Patients with a "currently active" second malignancy will be excluded with the exception of other non-melanoma skin cancers or cervical carcinoma in situ. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for 3 years
  • If human immunodeficiency virus (HIV) positive the HIV viral load must be < 200 copies/mL and CD4 count > 200. If an HIV positive patient is on highly active antiretroviral therapy (HAART) the patient must have been so for > 4 weeks
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Calculated creatinine clearance > 30 mL/min
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferases (AST) / alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
  • No history of the following:

    • Autoimmune disease (including inflammatory bowel disease) with the exception of patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment
    • Non-infectious pneumonitis that required steroids within 5 years
    • Organ transplant including prior stem cell transplant
    • Receipt of a live vaccine =< 4 weeks
    • Cerebral vascular accident/stroke within 6 months of enrollment
    • Myocardial infarction within 6 months of enrollment
    • Active unstable angina
    • Congestive heart failure (>= New York Heart Association Classification Class II)
    • Serious cardiac arrhythmia requiring medication. Whether an arrhythmia is considered "serious" is at the discretion of the investigator

Exclusion Criteria:

  • Active infection requiring systemic treatment
  • Use of immunosuppressive medication =< 7 days of registration, EXCEPT for the following:

    • Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);
    • Systemic corticosteroids at physiologic doses =< 10 mg/day of prednisone or equivalent;
    • Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication)."
  • Other severe acute or chronic medical conditions including but not limited to immune colitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
  • Chronic concomitant treatment that are strong inhibitors of CYP3A4 are not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study

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): NCT03944941


Contacts
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Contact: Dan P. Zandberg, MD 412-864-7955 zandbergdp@upmc.edu

Locations
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United States, Idaho
Saint Alphonsus Cancer Care Center-Boise Recruiting
Boise, Idaho, United States, 83706
Contact: Site Public Contact    734-712-3671    stephanie.couch@stjoeshealth.org   
Principal Investigator: Benjamin T. Marchello         
Saint Alphonsus Cancer Care Center-Caldwell Recruiting
Caldwell, Idaho, United States, 83605
Contact: Site Public Contact    734-712-3671    stephanie.couch@stjoeshealth.org   
Principal Investigator: Benjamin T. Marchello         
Kootenai Medical Center Recruiting
Coeur d'Alene, Idaho, United States, 83814
Contact: Site Public Contact    406-969-6060    mccinfo@mtcancer.org   
Principal Investigator: Benjamin T. Marchello         
Walter Knox Memorial Hospital Recruiting
Emmett, Idaho, United States, 83617
Contact: Site Public Contact    734-712-3671    stephanie.couch@stjoeshealth.org   
Principal Investigator: Benjamin T. Marchello         
Idaho Urologic Institute-Meridian Recruiting
Meridian, Idaho, United States, 83642
Contact: Site Public Contact    734-712-3671    stephanie.couch@stjoeshealth.org   
Principal Investigator: Benjamin T. Marchello         
Saint Alphonsus Medical Center-Nampa Recruiting
Nampa, Idaho, United States, 83686
Contact: Site Public Contact    734-712-3671    stephanie.couch@stjoeshealth.org   
Principal Investigator: Benjamin T. Marchello         
Kootenai Cancer Center Recruiting
Post Falls, Idaho, United States, 83854
Contact: Site Public Contact    406-969-6060    mccinfo@mtcancer.org   
Principal Investigator: Benjamin T. Marchello         
Kootenai Cancer Clinic Recruiting
Sandpoint, Idaho, United States, 83864
Contact: Site Public Contact    406-969-6060    mccinfo@mtcancer.org   
Principal Investigator: Benjamin T. Marchello         
United States, Iowa
Mary Greeley Medical Center Recruiting
Ames, Iowa, United States, 50010
Contact: Site Public Contact    515-956-4132      
Principal Investigator: Debra M. Prow         
McFarland Clinic PC - Ames Recruiting
Ames, Iowa, United States, 50010
Contact: Site Public Contact    515-956-4132      
Principal Investigator: Debra M. Prow         
McFarland Clinic PC-Boone Recruiting
Boone, Iowa, United States, 50036
Contact: Site Public Contact    515-956-4132      
Principal Investigator: Debra M. Prow         
Iowa Methodist Medical Center Recruiting
Des Moines, Iowa, United States, 50309
Contact: Site Public Contact    515-241-6727      
Principal Investigator: Robert J. Behrens         
Medical Oncology and Hematology Associates-Des Moines Recruiting
Des Moines, Iowa, United States, 50309
Contact: Site Public Contact    515-282-2921      
Principal Investigator: Robert J. Behrens         
Broadlawns Medical Center Recruiting
Des Moines, Iowa, United States, 50314
Contact: Site Public Contact    515-282-2200      
Principal Investigator: Robert J. Behrens         
Iowa Lutheran Hospital Recruiting
Des Moines, Iowa, United States, 50316
Contact: Site Public Contact    515-241-8704      
Principal Investigator: Robert J. Behrens         
McFarland Clinic PC-Trinity Cancer Center Recruiting
Fort Dodge, Iowa, United States, 50501
Contact: Site Public Contact    515-956-4132      
Principal Investigator: Debra M. Prow         
Trinity Regional Medical Center Recruiting
Fort Dodge, Iowa, United States, 50501
Contact: Site Public Contact    515-574-8302      
Principal Investigator: Robert J. Behrens         
McFarland Clinic PC-Jefferson Recruiting
Jefferson, Iowa, United States, 50129
Contact: Site Public Contact    515-956-4132      
Principal Investigator: Debra M. Prow         
McFarland Clinic PC-Marshalltown Recruiting
Marshalltown, Iowa, United States, 50158
Contact: Site Public Contact    515-956-4132      
Principal Investigator: Debra M. Prow         
Methodist West Hospital Recruiting
West Des Moines, Iowa, United States, 50266-7700
Contact: Site Public Contact    515-343-1000      
Principal Investigator: Robert J. Behrens         
United States, Montana
Community Hospital of Anaconda Recruiting
Anaconda, Montana, United States, 59711
Contact: Site Public Contact    406-969-6060    mccinfo@mtcancer.org   
Principal Investigator: Benjamin T. Marchello         
Billings Clinic Cancer Center Recruiting
Billings, Montana, United States, 59101
Contact: Site Public Contact    800-996-2663    research@billingsclinic.org   
Principal Investigator: Benjamin T. Marchello         
Bozeman Deaconess Hospital Recruiting
Bozeman, Montana, United States, 59715
Contact: Site Public Contact    406-969-6060    mccinfo@mtcancer.org   
Principal Investigator: Benjamin T. Marchello         
Benefis Healthcare- Sletten Cancer Institute Recruiting
Great Falls, Montana, United States, 59405
Contact: Site Public Contact    406-969-6060    mccinfo@mtcancer.org   
Principal Investigator: Benjamin T. Marchello         
Great Falls Clinic Recruiting
Great Falls, Montana, United States, 59405
Contact: Site Public Contact    406-969-6060    mccinfo@mtcancer.org   
Principal Investigator: Benjamin T. Marchello         
Saint Peter's Community Hospital Recruiting
Helena, Montana, United States, 59601
Contact: Site Public Contact    773-702-9171    protocols@AllianceNCTN.org   
Principal Investigator: Benjamin T. Marchello         
Kalispell Regional Medical Center Recruiting
Kalispell, Montana, United States, 59901
Contact: Site Public Contact    406-969-6060    mccinfo@mtcancer.org   
Principal Investigator: Benjamin T. Marchello         
Community Medical Hospital Recruiting
Missoula, Montana, United States, 59804
Contact: Site Public Contact    406-969-6060    mccinfo@mtcancer.org   
Principal Investigator: Benjamin T. Marchello         
United States, Oregon
Saint Alphonsus Medical Center-Baker City Recruiting
Baker City, Oregon, United States, 97814
Contact: Site Public Contact    734-712-3671    stephanie.couch@stjoeshealth.org   
Principal Investigator: Benjamin T. Marchello         
Saint Alphonsus Medical Center-Ontario Recruiting
Ontario, Oregon, United States, 97914
Contact: Site Public Contact    734-712-3671    stephanie.couch@stjoeshealth.org   
Principal Investigator: Benjamin T. Marchello         
United States, Pennsylvania
UPMC-Heritage Valley Health System Beaver Recruiting
Beaver, Pennsylvania, United States, 15009
Contact: Site Public Contact    724-773-7616      
Principal Investigator: Dan P. Zandberg         
UPMC Cancer Centers - Arnold Palmer Pavilion Recruiting
Greensburg, Pennsylvania, United States, 15601
Contact: Site Public Contact    724-838-1900      
Principal Investigator: Dan P. Zandberg         
UPMC Pinnacle Cancer Center/Community Osteopathic Campus Recruiting
Harrisburg, Pennsylvania, United States, 17109
Contact: Site Public Contact    717-724-6765    klitchfield@PINNACLEHEALTH.org   
Principal Investigator: Dan P. Zandberg         
University of Pittsburgh Cancer Institute (UPCI) Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Site Public Contact    412-647-8073      
Principal Investigator: Dan P. Zandberg         
UPMC-Shadyside Hospital Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Site Public Contact    412-621-2334      
Principal Investigator: Dan P. Zandberg         
UPMC-Passavant Hospital Recruiting
Pittsburgh, Pennsylvania, United States, 15237
Contact: Site Public Contact    412-367-6454      
Principal Investigator: Dan P. Zandberg         
United States, Wyoming
Billings Clinic-Cody Recruiting
Cody, Wyoming, United States, 82414
Contact: Site Public Contact    800-996-2663    research@billingsclinic.org   
Principal Investigator: Benjamin T. Marchello         
Welch Cancer Center Recruiting
Sheridan, Wyoming, United States, 82801
Contact: Site Public Contact    406-969-6060    mccinfo@mtcancer.org   
Principal Investigator: Benjamin T. Marchello         
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
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Study Chair: Dan P. Zandberg, MD University of Pittsburgh Medical Center Hillman Cancer Center

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Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT03944941     History of Changes
Other Study ID Numbers: A091802
NCI-2018-02652 ( Registry Identifier: NCI Clinical Trial Reporting Program )
U10CA180821 ( U.S. NIH Grant/Contract )
First Posted: May 10, 2019    Key Record Dates
Last Update Posted: June 5, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Skin Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Skin Diseases
Cetuximab
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs