Clinical Trials /

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

NCT03944941

Description:

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.

Related Conditions:
  • Skin Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Avelumab With or Without Cetuximab in Treating Patients With Advanced Skin Squamous Cell Cancer
  • Official Title: Phase II Randomized Trial of Avelumab Plus Cetuximab Versus Avelumab Alone in Advanced Cutaneous Squamous Cell Carcinoma of the Skin (cSCC)

Clinical Trial IDs

  • ORG STUDY ID: A091802
  • SECONDARY ID: NCI-2018-02652
  • SECONDARY ID: U10CA180821
  • NCT ID: NCT03944941

Conditions

  • Skin Squamous Cell Carcinoma
  • Metastatic Skin Cancer

Interventions

DrugSynonymsArms
AvelumabArm I (Avelumab)
CetuximabArm II (Avelumab, cetuximab)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (Avelumab)Active ComparatorPatients 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.
  • Avelumab
Arm II (Avelumab, cetuximab)ExperimentalPatients 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.
  • Avelumab
  • Cetuximab

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:The study will be declared promising if, after the 37th PFS event, the hazard ratio is less than 0.758.

Secondary Outcome Measures

Measure:Confirmed objective response rate (RR)
Time Frame:Up to 2 years post treatment
Safety Issue:
Description: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.
Measure:Clinical benefit rate (CBR)
Time Frame:Up to 2 years post treatment
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure:Overall Survival (OS)
Time Frame:Time between enrollment and or death, assessed up to 2 years post treatment
Safety Issue:
Description:The Kaplan-Meier method will be used to calculate a median OS as well as a 95% confidence interval.
Measure:Incidence of adverse events
Time Frame:Up to 30 days post treatment
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Alliance for Clinical Trials in Oncology

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