Patritumab With Cetuximab and a Platinum Agent for Squamous Cell Carcinoma (Cancer) of the Head and Neck (SCCHN )

Randomized, Placebo-controlled, Double-blind Phase 2 Study of Patritumab (U3-1287) in Combination With Cetuximab Plus Platinum-based Therapy in First Line Setting in Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

This study will test an investigational study drug called patritumab. It is a 'randomized study' which means participants have an equal chance of being assigned to receive the experimental medication (patritumab) or a substance that looks like the experimental product, but is not (placebo). Patritumab may work when combined with other medications that are approved for the treatment of head and neck cancer. They are called cetuximab, cisplatin or carboplatin. All participants will receive the other medications approved for treatment of head and neck cancer, even if they do not receive the experimental product.

Study Overview

• Status: Terminated
• Conditions: Head and Neck Neoplasms
• Intervention / Treatment: Drug: Patritumab; Drug: Cetuximab; Drug: Cisplatin; Drug: Carboplatin; Drug: Placebo

Detailed Description

Main objective of the trial:

The main objective of the trial is to evaluate progression-free survival (PFS) in the heregulin (HRG) high expression population from subjects treated with patritumab + cetuximab + platinum-based therapy compared to placebo + cetuximab + platinum-based therapy.

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • Institut Jules Bordet
  • Edegem, Belgium, 2650
    • Univeristair Ziekenhuis Antwerpen
  • Leuven, Belgium, 3000
    • UZ Leuven
• France
  • Angers cedex 02, France, 49055
    • Institut de cancerologie de l'ouest
  • Bordeaux, France, 33075
    • Centre Hospitalier de Bordeaux - Hôpital Saint André
  • Lyon, France, 69373
    • Centre Léon Bérard
  • Lyon, France, 69004
    • Hôpital Croix-Rousse
  • Marseille, France, 13008
    • Hopital Saint Joseph
  • Marseille, France, 13005
    • CHU Hôpital de la Timone
  • Montpellier, France, 34070
    • Centre de Cancerologie du Grand Montpellier
  • Saint-Herblain Cedex, France, 44805
    • Institut de cancerologie de l'ouest
  • Villejuif, France, 94805
    • Gustave Roussy
  • Cedex
    • Paris, Cedex, France, 75248
      • Institut Curie
• Germany
  • Berlin, Germany, 12200/12203
    • Charité Universitätsmedizin Berlin
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • München, Germany, 81377
    • Klinikum der Universität München
• Hungary
  • Budapest, Hungary, 1122
    • Orszagos Onkologiai Intezet
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Orvos-es Egészsegtudomanyi Centrum
  • Kecskemet, Hungary, 6000
    • Bacs-kiskun Megyei Korhaz
  • Miskolc, Hungary, 3526
    • Borsod Abaúj Zemplén Megyei Kórház és Egyetemi Oktató Kórház
  • Nyíregyháza, Hungary, 4400
    • Jósa András Oktatókórház
• Poland
  • Bydgoszcz, Poland, 85-796
    • Centrum Onkologii im. Prof. Franciszka Lukaszczyka w Bydgoszczy
  • Konin, Poland, 62-500
    • Przychodnia Lekarska "Komed"
  • Lodz, Poland, 93-513
    • Regionalny Osrodek Onkologiczny Szpital im. M. Kopernika w Lodzi
• Romania
  • Cluj-Napoca, Romania, 400058
    • Medisprof SRL
  • Craiova, Romania, 200347
    • Centrul de Oncologie Sfantul Nectarie
  • Iasi, Romania, 700483
    • Institutul Regional de Oncologie Iasi
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden NHS Foundation Trust
  • London, United Kingdom, SE1 7EH
    • Guy's and St Thomas' NHS Foundation Trust - St Thomas' Hospital
  • London, United Kingdom, NW1 2PG
    • University College London Hospitals NHS Foundation Trust - University College Hospital
  • Sheffield, United Kingdom, S10 2SJ
    • Weston Park Hospital
  • Shrewsbury, United Kingdom, SY3 8XQ
    • The Shrewsbury and Telford Hospital NHS Trust
  • Southampton, United Kingdom, SO16 6YD
    • Southampton General Hospital
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Has histologically confirmed recurrent disease or metastatic SCCHN tumor and/or from its lymph nodal metastases originating from the oral cavity, oropharynx, hypopharynx, and larynx
• Has or be willing to provide tumor tissue for testing
• Has measurable disease per Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1
• Has Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Has adequate hematological function per protocol
• Has adequate renal function per protocol
• Has adequate hepatic function per protocol
• Agrees to use effective contraception while on the study and for 6-months after the end of the study
• Provides written informed consent(s)

Exclusion Criteria:

• Has left ventricular ejection fraction (LVEF) <50%
• Had prior epidermal growth factor receptor (EGFR) targeted regimen
• Had prior anti-human epidermal growth factor receptor 3 (anti-HER3) therapy
• Had prior chemotherapy for recurrent/metastatic disease
• Had anti-cancer therapy between biopsy and submission of sample
• Has history of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated with no evidence of disease for ≥ 2 years
• Has known history of brain metastases or active brain metastases
• Has uncontrolled hypertension
• Has clinically significant electrocardiograph (ECG) findings
• Had myocardial infarction within 1 year before enrollment, symptomatic congestive heart failure, unstable angina, or arrhythmia requiring medication
• Had platinum-containing drug therapy with radiotherapy less than 6 months before study drug treatment
• Had therapeutic or palliative radiation therapy or major surgery within 4 weeks before study drug treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patritumab; All participants receive patritumab with cetuximab plus platinum-based therapy (cisplatin or carboplatin)	Drug: Patritumab; Patritumab initial loading dose is 18 mg/kg IV over 60 minutes followed by a maintenance dose of 9 mg/kg IV over 60 minutes (± 10 minutes) every three weeks; Other Names: U3-1287; Drug: Cetuximab; Cetuximab 400 mg/mg/m^2 IV loading dose, followed by 250 mg/m^2 weekly; Drug: Cisplatin; Cisplatin at 100 mg/m^2 IV infused over 1 hour, every three weeks up to a maximum of 6 cycles; Other Names: Platinum-based therapy; Drug: Carboplatin; Carboplatin IV over 30 to 60 minutes, every 3 weeks for a maximum of 6 cycles; Other Names: Platinum-based therapy
Placebo Comparator: Placebo; All participants receive placebo with cetuximab plus platinum-based therapy (cisplatin or carboplatin)	Drug: Cetuximab; Cetuximab 400 mg/mg/m^2 IV loading dose, followed by 250 mg/m^2 weekly; Drug: Cisplatin; Cisplatin at 100 mg/m^2 IV infused over 1 hour, every three weeks up to a maximum of 6 cycles; Other Names: Platinum-based therapy; Drug: Carboplatin; Carboplatin IV over 30 to 60 minutes, every 3 weeks for a maximum of 6 cycles; Other Names: Platinum-based therapy; Drug: Placebo; Placebo to match patritumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) in the Heregulin (HRG)-High Expression Population	PFS is defined as the time from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever comes first. Median PFS is from Kaplan-Meier analysis. Confidence interval (CI) for median was computed using Brookmeyer-Crowley method.	from Day 0 to end of active study (study termination) - within 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Overall Survival	Overall survival (OS) is defined as the time from the date of randomization to death due to any cause	at approximately 25 months
Percentage of Participants With Best Overall Response	Best overall response rate (ORR) is defined as the percentage of participants with Complete Response (CR) or Partial Response (PR)	at approximately 22 months

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.
• Investigators: Principal Investigator: Kevin Harrington, Prof, MD, Royal Marsden NHS Foundation Trust

Publications and helpful links

General Publications

• Forster MD, Dillon MT, Kocsis J, Remenar E, Pajkos G, Rolland F, Greenberg J, Harrington KJ. Patritumab or placebo, with cetuximab plus platinum therapy in recurrent or metastatic squamous cell carcinoma of the head and neck: A randomised phase II study. Eur J Cancer. 2019 Dec;123:36-47. doi: 10.1016/j.ejca.2019.08.017. Epub 2019 Oct 21.

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2015
• Primary Completion (Actual): January 11, 2018
• Study Completion (Actual): February 21, 2018

Study Registration Dates

• First Submitted: December 15, 2015
• First Submitted That Met QC Criteria: December 15, 2015
• First Posted (Estimate): December 17, 2015

Study Record Updates

• Last Update Posted (Actual): January 7, 2019
• Last Update Submitted That Met QC Criteria: December 12, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Head and neck cancer; Squamous cell carcinoma; Neoplasms by site; Squamous cell cancer of the head and neck
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Antineoplastic Agents; Antineoplastic Agents, Immunological; Carboplatin; Cisplatin; Cetuximab
• Other Study ID Numbers: U31287-A-U203; 2015-002222-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at http://www.clinicalstudydatarequest.com. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://www.clinicalstudydatarequest.com/Study-Sponsors-DS-Details.aspx
• IPD Sharing Time Frame: Studies for which the medicine and indication have received EU and US marketing approval on or after 01 January 2014 or by the US or EU Health Authorities when regulatory submissions in both regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States and the European Union from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No