Clinical Trials /

Paclitaxel Plus Cetuximab After First-line Checkpoint Inhibitor Failure

NCT04278092

Description:

Immune checkpoint inhibitors (CPI) such as pembrolizumab or nivolumab have been recently approved for the treatment of recurrent/metastatic head and neck cancer (HNSCC). However, only a minority of patients respond to therapy. From the clinical point of view the optimal management of patients progressing on or after CPI therapy is still a challenge. Retrospective analysis showed that HNSCC patients, who progressed on/after CPI, demonstrated an overall response rate (ORR) of up to 30% subsequent to chemotherapy +/- cetuximab treatment. It is the aim of this study to evaluate if paclitaxel plus cetuximab after first line pembrolizumab failure is an effective salvage therapy in 50 R/M HNSCC patients. The primary endpoint is ORR according to RECIST V 1.1.

Related Conditions:
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Oral Cavity Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Paclitaxel Plus Cetuximab After First-line Checkpoint Inhibitor Failure
  • Official Title: Paclitaxel Plus Cetuximab for the Treatment of Recurrent and/or Metastatic Head and Neck Cancer After First-line Checkpoint Inhibitor Failure: A Multicenter, Single Arm Study

Clinical Trial IDs

  • ORG STUDY ID: PACE ACE
  • NCT ID: NCT04278092

Conditions

  • Head and Neck Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
PaclitaxelPaclitaxel plus Cetuximab
CetuximabPaclitaxel plus Cetuximab

Purpose

Immune checkpoint inhibitors (CPI) such as pembrolizumab or nivolumab have been recently approved for the treatment of recurrent/metastatic head and neck cancer (HNSCC). However, only a minority of patients respond to therapy. From the clinical point of view the optimal management of patients progressing on or after CPI therapy is still a challenge. Retrospective analysis showed that HNSCC patients, who progressed on/after CPI, demonstrated an overall response rate (ORR) of up to 30% subsequent to chemotherapy +/- cetuximab treatment. It is the aim of this study to evaluate if paclitaxel plus cetuximab after first line pembrolizumab failure is an effective salvage therapy in 50 R/M HNSCC patients. The primary endpoint is ORR according to RECIST V 1.1.

Trial Arms

NameTypeDescriptionInterventions
Paclitaxel plus CetuximabExperimentalPaclitaxel combination with weekly cetuximab will be administered for up to six cycles. Thereafter weekly cetuximab maintenance will be given.
  • Paclitaxel
  • Cetuximab

Eligibility Criteria

        Inclusion Criteria:

          -  The patient has provided written informed consent prior to any study-related
             procedure.

          -  The patient is at least 18 years of age

          -  Histologically proven locally advanced unresectable, recurrent and/or metastatic
             squamous cell carcinoma of the oropharynx, hypopharynx, larynx or oral cavity not
             amenable for salvage surgery

          -  p16 status has to be determined for oropharyngeal carcinomas

          -  Documented progressive disease based on investigator assessment according to RECIST
             1.1, following receipt of a pembrolizumab based regimen given as first line therapy
             for R/M SCCHN

          -  Measurable disease according to RECIST 1.1.

          -  The patient has a life expectancy of at least 3 months.

          -  Has a performance status of ≤ 2 on the ECOG Performance Scale

          -  Female patient of childbearing potential should have a negative urine or serum
             pregnancy prior to study . If the urine test is positive or cannot be confirmed as
             negative, a serum pregnancy test will be required.

          -  Female patients of childbearing potential should be willing to use 2 methods of birth
             control or be surgically sterile, or abstain from heterosexual activity for the course
             of the study until 120 days after the last dose of study medication. Patients of
             childbearing potential are those who have not been surgically sterilized or have not
             been free from menses for > 1 year.

          -  Male patients should agree to use an adequate method of contraception starting with
             the first dose of study therapy until 120 days after the last dose of study therapy.

          -  Demonstrate adequate organ function as defined in table 1, all screening labs should
             be performed within 14 days of treatment initiation.

        Exclusion Criteria:

          -  Prior taxane therapy is not allowed except as part of induction therapy for locally
             advanced disease (completed at least 6 months before study entry)

          -  Prior cetuximab therapy is not allowed except as part of either induction therapy or
             in combination with radiotherapy treatment for locally advanced disease (completed at
             least 6 months before study entry)

          -  Patients with nasopharyngeal carcinomas or salivary glands cancers

          -  Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy within 4 weeks of the first
             dose of treatment.

          -  Has a diagnosis of immunodeficiency including a known history of Human
             Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

          -  Has known active Hepatitis A/B or Hepatitis C

          -  Has had prior pembrolizumab within 2 weeks prior to study day 1 or who has not
             recovered (i.e., recovery to ≤ Grade 1 or baseline grade prior to pembrolizumab) from
             (immune- related) adverse events other than endocrine side effects.

          -  Has had prior chemotherapy or radiation therapy within 2 weeks prior to study day 1 or
             who has not recovered (i.e., recovery to ≤ Grade 1 or baseline grade prior to
             pembrolizumab) from adverse events due to a previously administered agent.

          -  Has had chemotherapy, targeted therapy or investigational drugs after checkpoint
             inhibitor failure for second line therapy .

          -  Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer.

          -  Has an active infection requiring systemic therapy.

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the patient's
             participation for the full duration of the trial, or is not in the best interest of
             the patient to participate, in the opinion of the treating investigator.

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             until 120 days after the last dose of trial treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate
Time Frame:3 months
Safety Issue:
Description:To evaluate the Overall Response Rate (CR/PR) rate according to RECIST V 1.1

Secondary Outcome Measures

Measure:Median Overall Survival
Time Frame:2 years
Safety Issue:
Description:The interval between start of treatment and death from any cause
Measure:Median Progression Free Survival
Time Frame:2 years
Safety Issue:
Description:The interval between start of treatment and date of progression, or death, from any cause
Measure:Median Duration of response
Time Frame:2 years
Safety Issue:
Description:
Measure:Health-related quality-of-life scores per patient measured according to the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) C-30 scoring manual
Time Frame:2 years
Safety Issue:
Description:
Measure:Health-related quality-of-life scores per patient measured according to the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) H&N35 scoring manual
Time Frame:2 years
Safety Issue:
Description:
Measure:Number of participants with adverse events
Time Frame:2 years
Safety Issue:
Description:AEs, treatment-related AEs, serious adverse events (SAEs), and treatment-related SAEs will be tabulated using worst grade per NCI CTCAE v 5.0 criteria.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Medical University of Vienna

Last Updated

March 2, 2020