Paclitaxel Plus Cetuximab After First-line Checkpoint Inhibitor Failure

• ClinicalTrials.gov Identifier: NCT04278092
• Recruitment Status: Recruiting
• First Posted: February 20, 2020
• Last Update Posted: March 16, 2023
• Sponsor: Medical University of Vienna
• Information provided by (Responsible Party): Thorsten Fuereder, Medical University of Vienna

Tracking Information

• First Submitted Date: February 18, 2020
• First Posted Date: February 20, 2020
• Last Update Posted Date: March 16, 2023
• Actual Study Start Date: February 10, 2020
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 19, 2020)

Overall response rate [ Time Frame: 3 months ]

To evaluate the Overall Response Rate (CR/PR) rate according to RECIST V 1.1

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 2, 2020)

• Median Overall Survival [ Time Frame: 2 years ]
  The interval between start of treatment and death from any cause
• Median Progression Free Survival [ Time Frame: 2 years ]
  The interval between start of treatment and date of progression, or death, from any cause
• Median Duration of response [ Time Frame: 2 years ]
• 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 ]
• 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 ]
• Number of participants with adverse events [ Time Frame: 2 years ]
  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.

Original Secondary Outcome Measures (submitted: February 19, 2020)

• Median Overall Survival [ Time Frame: 2 years ]
  The interval between start of treatment and death from any cause
• Median Progression Free Survival [ Time Frame: 2 years ]
  The interval between start of treatment and date of progression, or death, from any cause
• Median Duration of response [ Time Frame: 2 years ]
• To report changes in the in 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 ]
• To report changes in the in 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 ]
• Number of participants with adverse events [ Time Frame: 2 years ]
  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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Head and Neck Squamous Cell Carcinoma

Intervention

• Drug: Paclitaxel
  Paclitaxel 175 mg/m2, q21
  Other Name: Taxol
• Drug: Cetuximab
  Cetuximab 400mg/m2 loading dose followed by weekly 250mg/m2
  Other Name: Erbitux

Study Arms

Experimental: Paclitaxel plus Cetuximab

Paclitaxel combination with weekly cetuximab will be administered for up to six cycles. Thereafter weekly cetuximab maintenance will be given.

Interventions:

• Drug: Paclitaxel
• Drug: Cetuximab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 19, 2020): 50
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2024
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Christina Wagner; +43140400 ext 72750; christina.wagner@meduniwien.ac.at

• Listed Location Countries: Austria

Administrative Information

• NCT Number: NCT04278092
• Other Study ID Numbers: PACE ACE
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Thorsten Fuereder, Medical University of Vienna
• Original Responsible Party: Same as current
• Current Study Sponsor: Medical University of Vienna
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Thorsten Fuereder, MD; Medical University of Vienna

• PRS Account: Medical University of Vienna
• Verification Date: March 2023