ERBITUX® Followed by Adjuvant Treatment With Chemoradiation and ERBITUX® for Locally Advanced Head and Neck Squamous Cell Carcinoma

NCT01218048 | Completed Phase 2 Results DMC

• 1 other identifier: UPCI 08-013
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

There are currently no useful tests to identify patients who will respond to cetuximab therapy, notably because EGFR levels do not correlate with the clinical responses observed. Thus, the investigators are investigating the role of cellular immunity and immune escape mechanisms to explain the differential clinical response to cetuximab.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Keywords

Carcinoma; Head and Neck; Cetuximab; Locally Advanced Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (3)

• NK Cell Activation

  Cetuximab-mediated NK cell activation (percentage of activity) measures at pre-/post-cetuximab exposure for patients in peripheral blood lymphocytes (PBL) and tumor infiltrating lymphocytes (TIL) and in those patients that did and did not respond to treatment.

  Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)

• Serum Cytokines Levels

  Serum cytokines levels measured at pre-/post-cetuximab, exposure measured in picogram per milliliter of plasma (pg/ml)

  Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)

• T Cell Activation

  T cell activation measured at pre-/post-cetuximab exposure

  Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)

Secondary Outcomes (6)

• Frequency of EGFR-specific T Cells (EGFR853-861 Peptide-specific Tetramer+ CD8+T Cells)

  Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)

• Progression-free Survival (PFS)

  Up to 54 months

• Overall Survival (OS)

  Up to 2 years

• Objective Response (Rate)

  Up to 2 years

• 3-year Progression-free Survival (PFS)

  3 years

Study Arms (1)

Neo-Adjuvant Cetuximab

EXPERIMENTAL

Neo-Adjuvant Cetuximab + Surgery + Post-Surgical Radiation + Cisplatin (or Carboplatin) NOTE: Based the results of surgery if the treating physician feels patient is not a candidate for chemotherapy, radiation can be given alone or with cetuximab.

Drug: Cetuximab; Procedure: Surgery; Radiation: Post-surgical radiation; Drug: Cisplatin or carboplatin

Interventions

Cetuximab DRUG

Pre-Surgery: IV, 400 mg/m2 day 1 then 250 mg/m2 alone days 8 and 15; Post-surgery: IV, 250 mg/m2 weekly concurrent with RT

Also known as: ERBITUX®

Neo-Adjuvant Cetuximab

Surgery PROCEDURE

Surgery for tumor

Neo-Adjuvant Cetuximab

Post-surgical radiation RADIATION

Radiation (2 Gy/d) to min of 60 Gy + max of 66 Gy post-surgery

Neo-Adjuvant Cetuximab

Cisplatin or carboplatin DRUG

Cisplatin 30 mg/m2 or carboplatin AUC 1.5-2/week weekly, Concurrent with radiotherapy

Neo-Adjuvant Cetuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed, previously untreated HNC. Clinical stage III or IVA disease without distant metastases as determined by CT, and as defined by the American Joint Committee on Cancer Staging System, Sixth edition (See Appendix I).
• Primary tumors of the oral cavity, oropharynx, hypopharynx, or larynx will be included. Primary tumors of the sinuses, paranasal sinuses, or nasopharynx, or unknown primary tumors are NOT allowed.
• Macroscopic complete resection of the primary tumor must be planned.
• Age greater than or equal to 18 years.
• ECOG performance status 0-1.
• Adequate hematologic, renal and hepatic function, as defined by:
• Absolute neutrophil count (ANC) greater than or equal to 1,500/ul, platelets greater than or equal to 100,000/ul.
• Creatinine clearance \> 40
• Bilirubin less than or equal to 1.5 x ULN, AST or ALT less than or equal to 2.5 x ULN.
• Have signed written informed consent.

You may not qualify if:

• Subjects who fail to meet the above criteria.
• Prior severe infusion reaction to a monoclonal antibody.
• Pregnancy or breastfeeding. Women of childbearing potential (WOCBP) must practice acceptable methods of birth control to prevent pregnancy. Prior to study enrollment, WOCBP must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control.
• All WOCBP MUST have a negative pregnancy test within 7 days prior to first receiving investigational product. If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study. In addition, all WOCBP should be instructed to contact the Investigator immediately if they suspect they might be pregnant (e.g., missed or late menstrual period) at any time during study participation. The Investigator must immediately notify BMS in the event of a confirmed pregnancy in a patient participating in the study.
• Subjects with an ECOG performance status of 2 or worse.
• Evidence of distant metastasis.
• Any other malignancy active within 5 years except for non-melanoma skin cancer or carcinoma in situ of the cervix, DCIS or LCIS of the breast.
• Prior history of HNC.
• Prior therapy targeting the EGFR pathway.
• Any unresolved chronic toxicity greater than or equal to grade 2 from previous anticancer therapy (except alopecia), according to Common Terminology Criteria for Adverse Events v4.0 (CTCAE).
• Acute hepatitis, known HIV, or active uncontrolled infection.
• History of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, myocardial infarction within prior 6 months, untreated known coronary artery disease, uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction.
• Uncontrolled peptic or gastric ulcer disease, or gastrointestinal bleeding within prior 6 months.
• Active alcohol abuse or other illness that carries a likelihood of inability to comply with study treatment and follow-up.
• Treatment with a non-approved or investigational drug within 30 days prior to Day 1 of study treatment.

Sponsors & Collaborators

• Robert Ferris: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

UPCI - Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (1)

• Li J, Srivastava RM, Ettyreddy A, Ferris RL. Cetuximab ameliorates suppressive phenotypes of myeloid antigen presenting cells in head and neck cancer patients. J Immunother Cancer. 2015 Nov 17;3:54. doi: 10.1186/s40425-015-0097-6. eCollection 2015.

  PMID: 26579227 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Carcinoma

Interventions

Cetuximab; Surgical Procedures, Operative; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Robert Ferris, MD, PhD
• Organization: University of Pittsburgh Cancer Institute

ferrrl@upmc.edu

412-623-3205

Study Officials

• Rober L Ferris, MD, PhD

  University of Pittsburgh Med Ctr (UPCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: October 7, 2010
• First Posted: October 8, 2010
• Study Start: February 1, 2011
• Primary Completion: November 4, 2015
• Study Completion: February 14, 2017
• Last Updated: August 16, 2018
• Results First Posted: August 16, 2018

Record last verified: 2018-07

Locations

US (1)