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Trial record 1 of 1 for:    NCT02128906
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Radiotherapy With Cisplatin vs. Docetaxel-cetuximab in HNSCC: ERCC1 Biomarker Enrichment and Interaction Design ((UPCI)13-056)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by University of Pittsburgh
Sponsor:
Information provided by (Responsible Party):
Dwight Heron, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT02128906
First received: April 29, 2014
Last updated: November 1, 2016
Last verified: November 2016
  Purpose

The goal of this clinical research study is to learn which chemotherapy combination may be more effective in treating locally advanced head and neck squamous cell carcinoma (HNSCC). The side effects of these combinations will also be studied.

This study treatment consists of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy. For study chemotherapy, patients will be randomized between cisplatin or the combination of docetaxel and cetuximab. Subjects will be stratified depending on HPV status and the presence of ERCC-1 [4F9] in the tumor prior to randomization. The study will evaluate cisplatin vs. docetaxel-cetuximab in the overall population, and test which radiation and chemotherapy combination works best in relationship to how much ERCC-1 [4F9] is expressed in a tumor.


Condition Intervention Phase
Squamous Cell Carcinoma
Drug: Cisplatin
Radiation: IMRT
Drug: Docetaxel
Drug: Cetuximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Phase II Study of Definitive Radiotherapy With Concurrent Cisplatin vs. Docetaxel-cetuximab in Locally Advanced Head and Neck Squamous Cell Carcinoma: an ERCC1 Biomarker Enrichment and Interaction Design

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Evaluate the efficacy of radiotherapy with concurrent docetaxel-cetuximab vs. cisplatin in patients with locally advanced HNSCC and increased tumoral ERCC1 expression, as measured by time to progression (TTP) [ Time Frame: 5 years ]

Secondary Outcome Measures:
  • Evaluate the efficacy of radiotherapy with concurrent docetaxel-cetuximab vs. cisplatin in patients with PULA HNSCC and decreased/normal tumoral ERCC1 expression, as measured by TTP [ Time Frame: 5 years ]
  • Evaluate the efficacy of radiotherapy with concurrent docetaxel-cetuximab vs. cisplatin in all patients irrespective of ERCC1 status, as measured by TTP [ Time Frame: 5 years ]
  • Prospectively validate the candidate cutpoint for decreased/normal vs. increased ERCC1 [4F9] expression in patients treated with cisplatin-IMRT [ Time Frame: 5 years ]
  • Prospectively investigate two sets of radiologic interpretive criteria, including RECIST 1.1 and integrated PET/CT, for the designation of complete response (CR), and to compare the ability of the two CR classifications to accurately predict 2-year TTP. [ Time Frame: 5 years ]

Estimated Enrollment: 160
Study Start Date: December 2013
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Cisplatin-IMRT
Cisplatin 40 mg/m2 weekly x 7; IMRT: once daily, M-F, 7 weeks (70 Gy)
Drug: Cisplatin
Cisplatin 40 mg/m2 weekly x 7
Other Name: Platinol
Radiation: IMRT
IMRT: once daily, M-F, 7 weeks (70 Gy)
Active Comparator: Docetaxel-Cetuximab-IMRT
Docetaxel 15 mg/m2 weekly x 7; Cetuximab 400 mg/m2 load, one week prior to IMRT; Cetuximab 250 mg/m2 weekly x 7; IMRT: once daily, M-F, 7 weeks (70 Gy)
Radiation: IMRT
IMRT: once daily, M-F, 7 weeks (70 Gy)
Drug: Docetaxel
Docetaxel 15 mg/m2 weekly x 7
Other Name: Taxotere
Drug: Cetuximab
Cetuximab 400 mg/m2 load, one week prior to IMRT Cetuximab 250 mg/m2 weekly x 7
Other Name: Erbitux

Detailed Description:

If randomized to the cisplatin arm, you will receive cisplatin, 40 mg/m2, administered intravenously (IV) once a week (+/- 2 days) for 7 weeks. Per investigator discretion, if radiation continues beyond 7 weeks due to technical factors (not toxicity delays), an 8th dose of concurrent cisplatin may be added.

It is strongly preferred that cisplatin be administered on Monday, Tuesday, or Wednesday of each treatment week to maximize overlap with radiation; administration on Thursday or Friday for logistical purposes will be noted however will not constitute a protocol violation. Cisplatin can be given either before or after the radiation therapy fraction that is given on the same day. If a dose of cisplatin is omitted when radiotherapy is ongoing, it will not be made up or added to the end of treatment. The omitted dose and the reason for the omission should be recorded in the site's source documentation. If radiotherapy is held, cisplatin should be held during the treatment break and resumed when radiation restarts. In this case, the cisplatin dose is not considered skipped or omitted, but delayed.

If you are randomized to arm you will receive cetuximab, 250 mg/m2, IV over 60 minutes on a weekly schedule (+/- 2 days). . Cetuximab may be administered either before or after the radiation fraction that is given on the same day. Docetaxel will be administered at least 30 minutes following cetuximab. It is not permitted to make up missed doses of cetuximab or docetaxel. If a radiation therapy treatment break occurs, cetuximab should be held. When radiation restarts, cetuximab should resume.

It is strongly preferred that cetuximab be administered on Monday, Tuesday, or Wednesday of each treatment week to maximize overlap with radiation; administration on Thursday or Friday for logistical purposes will be noted however will not constitute a protocol violation. Cetuximab will be given once a week (+/- 2 days) for a total of 7 doses concurrent with radiation therapy and docetaxel.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pathologically confirmed squamous cell carcinoma, undifferentiated carcinoma, or poorly differentiated carcinoma of the oropharynx, larynx, or hypopharynx with no evidence of distant metastasis. Biopsy sampling of primary tumor with pathology report documenting diagnostic tissue type is required.
  • Patients must have stage III, IVa or IVb disease as determined by imaging studies and complete head and neck exam. Staging evaluation should be in accordance with the American Joint Committee on Cancer Staging Manual, 7th edition.
  • Patients with oropharyngeal squamous cell carcinoma may have p16(+) or p16(-) disease; in these patients, p16 status must be known prior to randomization. Assessment of p16 status may occur locally or centrally. Note: The definition of p16(+) disease is diffuse nuclear and cytoplasmic staining in ≥ 70% of tumor cells.
  • Patients must be untreated with curative-intent surgery for current diagnosis of Stage III, IVa, or IVb disease. Diagnostic biopsy of primary tumor and/or nodal sites is permitted.
  • Diagnostic simple tonsillectomy is permitted, provided patient has RECIST-measurable residual tumor and/or nodal disease.
  • Patients with a second HNSCC primary tumor are eligible for this study, provided more than 2 years have elapsed since the first diagnosis of HNSCC, the original tumor was managed with surgery only (no adjuvant chemotherapy/radiotherapy), and has not recurred.
  • Patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0 resected differentiated thyroid carcinoma, who are eligible.
  • No prior systemic treatment (chemotherapy or biologic/molecular targeted therapy) or radiation treatment for head and neck cancer.
  • Patients may have received chemotherapy or radiation for a previous, curatively treated non-HNSCC malignancy, provided at least 2 years have elapsed.
  • Patients must be untreated with radiation above the clavicles.
  • Patients with a history of curatively-treated non-HNSCC malignancy must be disease-free for at least 2 years except for carcinoma-in-situ of cervix, non-melanomatous skin cancer, or T1-2, N0, M0 resected differentiated thyroid carcinoma.
  • Diagnostic primary tumor tissue must be available for ERCC1 staining
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 (See Appendix 8)
  • Age ≥ 18
  • Patients must have measurable disease according to RECIST 1.1
  • Patients must have the following laboratory values measured within 14 days of registration:
  • Absolute neutrophil count (ANC) > 1500/mm3
  • Hemoglobin (Hb) > 8.0 g/dL
  • Platelet count (PLT) > 100,000/mm3
  • Creatinine clearance ≥ 45 ml/min determined by 24-hour collection or estimated by the Cockraft-Gault formula:

Calculated Creatinine Clearance = [(140-age) X (actual body weight in kg) X (0.85 if female)]/(72 X serum creatinine)

  • Serum bilirubin < 2 mg/dL
  • AST (aspartate aminotransferase) and ALT (alanine aminotransferase) < 3 times upper limit of normal (ULN)
  • The following assessments are required within 14 days prior to registration: Na, K, Cl, glucose, Ca, Mg, and albumin. The following metabolic values will exclude patients from study enrollment:
  • Serum calcium (ionized or adjusted for albumin) < 7 mg/dl (1.75 mmol/L) or > 12.5 mg/dl (> 3.1 mmol/L) despite intervention to normalize levels
  • Magnesium < 0.9 mg/dl (< 0.4 mmol/L) or > 3 mg/dl (> 1.23 mmol/L) despite intervention to normalize levels
  • Potassium < 3.5 mmol/L or > 6 mmol/L despite intervention to normalize levels
  • Sodium < 130 mmol/L or > 155 mmol/L despite intervention to normalize levels Note: Patients with an initial magnesium < 0.5 mmol/L (1.2 mg/dl) may receive corrective magnesium supplementation but should continue to receive either prophylactic weekly infusion of magnesium and/or oral magnesium supplementation (eg, magnesium oxide) at the investigator's discretion.
  • No prior severe infusion reaction to a monoclonal antibody
  • Written informed consent must be obtained from all patients prior to beginning therapy. Patients should have the ability to understand and the willingness to sign a written informed consent document.
  • Informed consent must be obtained from all patients prior to beginning therapy, including consent for mandatory tissue submission for ERCC1 staining (and p16 staining if not locally conducted). Patients should have the ability to understand and the willingness to sign a written informed consent document.
  • No unstable angina or myocardial infarction within the prior 6 months; no symptomatic congestive heart failure; no serious cardiac arrhythmia requiring medication; no cerebrovascular ischemia or stroke within the past 6 months.
  • No uncontrolled intercurrent illness including active infection, uncontrolled diabetes, uncontrolled hypertension, or uncontrolled psychiatric illness which in the investigator's opinion would limit compliance with study requirements or compromise patient safety.
  • Women must not be pregnant or breast feeding because chemotherapy and/or cetuximab may be harmful to the fetus or the nursing infant. Pregnant women are excluded from this study because chemotherapy and/or cetuximab have the potential for teratogenic or abortifacient effects.
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while in this study, she should inform her treating physician immediately. All females of childbearing potential must have a blood test or urine study within 14 days of registration to rule out pregnancy.
  • HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible drug interactions with study drugs. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated. Note: HIV testing is not required for entry into this protocol.
  • Patients may not be receiving any other anti-neoplastic investigational agents.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02128906

Contacts
Contact: Karen Holeva, RN (412) 623-1275 holevakd@upmc.edu

Locations
United States, Pennsylvania
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Karen Holeva, RN    412-623-1275    holevakd@upmc.edu   
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Dwight Heron, MD University of Pittsburgh
  More Information

Responsible Party: Dwight Heron, MD, FACRO, FACR, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02128906     History of Changes
Other Study ID Numbers: UPCI 13-056
Study First Received: April 29, 2014
Last Updated: November 1, 2016

Keywords provided by University of Pittsburgh:
ERCC1
squamous cell carcinoma
oropharynx
larynx
hypopharynx
p16
radiotherapy
docetaxel
cetuximab
cisplatin
EGFR
Biomarker
efficacy
head and neck
tongue
throat

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Docetaxel
Cisplatin
Cetuximab
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on March 22, 2017