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Radiation Therapy With or Without Cisplatin in Treating Patients With Stage III-IVA Squamous Cell Carcinoma of the Head and Neck Who Have Undergone Surgery

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ClinicalTrials.gov Identifier: NCT02734537
Recruitment Status : Recruiting
First Posted : April 12, 2016
Last Update Posted : August 2, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )

Study Description
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Brief Summary:
This phase II trial studies how well radiation therapy with or without cisplatin works in treating patients with stage III-IVA squamous cell carcinoma of the head and neck who have undergone surgery. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known if radiation therapy is more effective with or without cisplatin in treating patients with squamous cell carcinoma of the head and neck.

Condition or disease Intervention/treatment Phase
Head and Neck Squamous Cell Carcinoma Hypopharyngeal Squamous Cell Carcinoma Laryngeal Squamous Cell Carcinoma Laryngeal Squamous Cell Carcinoma, Spindle Cell Variant Lip and Oral Cavity Squamous Cell Carcinoma p16INK4a Negative Oropharyngeal Squamous Cell Carcinoma Stage III Hypopharyngeal Carcinoma AJCC v8 Stage III Laryngeal Cancer AJCC v8 Stage III Lip and Oral Cavity Cancer AJCC v8 Stage III Oral Cavity Verrucous Carcinoma Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8 Stage IVA Hypopharyngeal Carcinoma AJCC v8 Stage IVA Laryngeal Cancer AJCC v8 Stage IVA Lip and Oral Cavity Cancer AJCC v8 Stage IVA Oral Cavity Verrucous Carcinoma Stage IVA Oropharyngeal (p16-Negative) Carcinoma AJCC v8 Drug: Cisplatin Radiation: Intensity-Modulated Radiation Therapy Other: Laboratory Biomarker Analysis Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the disease-free survival (DFS) of patients with stage III-IV squamous cell carcinoma of the head and neck (SCCHN) and disruptive p53 mutations after primary surgical resection followed by postoperative radiotherapy (PORT) alone or PORT with concurrent cisplatin.

SECONDARY OBJECTIVES:

I. To evaluate the DFS of patients with stage III-IV SCCHN and non-disruptive p53 mutations after primary surgical resection followed by PORT alone or PORT with concurrent cisplatin.

II. To evaluate the DFS of patients with stage III-IV SCCHN and p53 wild type after primary surgical resection followed by PORT alone or PORT with concurrent cisplatin.

III. To evaluate toxicities of PORT alone or PORT with concurrent cisplatin. IV. To evaluate p53 mutation as a predictive biomarker of survival benefit given post-operative concurrent radiation and cisplatin.

V. To identify potential genomic alterations in addition to TP53 mutations that may be developed to a novel treatment approach.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients undergo intensity-modulated radiation therapy (IMRT) once daily (QD) 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.

ARM B: Patients undergo IMRT QD 5 days a week and receive cisplatin intravenously (IV) over 1-2 hours weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 3 years and then every 12 months for 7 years.


Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 345 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Randomized Trial of Radiotherapy With or Without Cisplatin for Surgically Resected Squamous Cell Carcinoma of the Head and Neck (SCCHN) With TP53 Sequencing
Actual Study Start Date : March 29, 2016
Estimated Primary Completion Date : May 1, 2022
Estimated Study Completion Date : May 1, 2027

Resource links provided by the National Library of Medicine

Drug Information available for: Cisplatin

Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm A (IMRT)
Patients undergo IMRT QD 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.
 Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy

Other: Laboratory Biomarker Analysis
Correlative studies
Experimental: Arm B (IMRT, cisplatin)
Patients undergo IMRT QD 5 days a week and receive cisplatin IV over 1-2 hours weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.
 Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin

Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy

Other: Laboratory Biomarker Analysis
Correlative studies


Outcome Measures
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Primary Outcome Measures :
  1. Disease-free survival in patients with stage III-IV disease and disruptive p53 mutation [ Time Frame: Date of randomization to the date of recurrence, second primary tumor from the head and neck region, or death, assessed up to 10 years ]
    Kaplan-Meier estimates will be used to estimate event-time distributions and comparison between arms will be performed using a log-rank test.


Secondary Outcome Measures :
  1. Disease-free survival in patients with stage III-IV disease and non-disruptive p53 mutation [ Time Frame: Date of randomization to the date of recurrence, second primary tumor from the head and neck region, or death, assessed up to 10 years ]
    Kaplan-Meier estimates will be used to estimate event-time distributions and comparison between arms will be performed using a log-rank test.

  2. Disease-free survival in patients with stage III-IV disease and wild type p53 mutation [ Time Frame: Date of randomization to the date of recurrence, second primary tumor from the head and neck region, or death, assessed up to 10 years ]
    Kaplan-Meier estimates will be used to estimate event-time distributions and comparison between arms will be performed using a log-rank test.

  3. Incidence of adverse events graded using Common Terminology Criteria for Adverse Events version 4 [ Time Frame: Up to 6 weeks ]
    Toxicity will be examined by arm and compared using the Fisher's exact test.

  4. p53 as a predictive marker of recurrence [ Time Frame: Baseline ]
    To evaluate whether p53 is a predictive marker, a p53 by treatment arm interaction term will be tested in a Cox proportional hazards model.


Eligibility Criteria
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Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • PRE-REGISTRATION (STEP 0)
  • Pathologically proven diagnosis of squamous cell carcinoma (including variants such as verrucous carcinoma, spindle cell carcinoma, carcinoma not otherwise specified [NOS]) of the head/neck (oral cavity, oropharynx, hypopharynx or larynx); pathologic stage III or IVA (American Joint Committee on Cancer [AJCC] 8): T3-T4a, N0-3, M0 or T1-T2, N1-3, M0

  • Patient has undergone total resection of the primary tumor with curative intent

    • NOTE: Patient is to be pre-registered to screening (Step 0) and tissue submitted to Foundation Medicine as soon as possible after surgery in order to meet the 8 week deadline to register the patient to Step 1 after surgery; full assay minimum turn-around time is 17-24 days
  • For oropharynx primary tumors, the patient must have negative human papillomavirus (HPV) status of the tumor as determined by p16 protein expression using immunohistochemistry (IHC)
  • Patients with, per the operative and/or pathology report, positive margin(s) (tumor present at the cut or inked edge of the tumor) which is not superceded by an additional margin of tumor-negative tissue, nodal extracapsular extension, and/or gross residual disease after surgery are not eligible

  • A paraffin-embedded surgical tumor tissue specimen has been located is available for shipment to Foundation Medicine, Inc. following pre-registration

    • NOTE: Complete the EA3132-specific FoundationOne requisition form
  • Patients with a history of a curatively treated malignancy must be disease-free for at least two years except for carcinoma in situ of cervix and/or non-melanomatous skin cancer; patients must not have received chemotherapy or investigational therapy within two years of surgical resection of the primary tumor
  • Patient must not have had previous irradiation to the head and neck that would result in overlap in radiation fields for the current disease
  • Patients with recurrent disease or multiple primaries are ineligible
  • RANDOMIZATION (STEP 1)
  • NOTE: Patient must meet all eligibility criteria outlined in pre-registration; patient may not be randomized until site has been notified that the central determination of p53 mutation status of the surgical tumor tissue has been completed and site has been notified of assay completion
  • Per the operative report, the gross total resection of the primary tumor with curative intent was completed within 8 weeks prior to randomization

  • The patient must have the following assessments done =< 8 weeks prior to randomization:

    • Examination by a head and neck surgeon
    • Chest x-ray (or chest computed tomography [CT] scan or CT/positron emission tomography [PET] of the chest or magnetic resonance imaging [MRI]) to rule out distant metastatic disease
  • Patient has Eastern Cooperative Oncology Group (ECOG) performance status 0-1 within 2 weeks prior to randomization
  • Women must not be pregnant or breast-feeding; females of childbearing potential must have a blood or urine study within 2 weeks prior to randomization to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study and until 60 days from the last study treatment
  • Absolute neutrophil count >= 1,500/mm^3 within 4 weeks prior to randomization
  • Platelets >= 100,000/mm^3 within 4 weeks prior to randomization
  • Total bilirubin =< the upper limit of normal (ULN) within 4 weeks prior to randomization
  • Calculated creatinine clearance must be > 60 ml/min using the Cockcroft-Gault formula within 4 weeks prior to randomization
  • Patient must not have an intercurrent illness likely to interfere with protocol therapy
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02734537


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Sponsors and Collaborators
ECOG-ACRIN Cancer Research Group
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Robert Ferris ECOG-ACRIN Cancer Research Group
More Information
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Responsible Party: ECOG-ACRIN Cancer Research Group
ClinicalTrials.gov Identifier: NCT02734537     History of Changes
Other Study ID Numbers: EA3132
NCI-2015-01911 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
EA3132 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
EA3132 ( Other Identifier: CTEP )
U10CA180820 ( U.S. NIH Grant/Contract )
First Posted: April 12, 2016    Key Record Dates
Last Update Posted: August 2, 2018
Last Verified: July 2018
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Carcinoma, Squamous Cell
Carcinoma, Verrucous
Squamous Cell Carcinoma of Head and Neck
Laryngeal Neoplasms
Mouth Neoplasms
Lip Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Head and Neck Neoplasms
 Neoplasms by Site
Otorhinolaryngologic Neoplasms
Laryngeal Diseases
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Otorhinolaryngologic Diseases
Mouth Diseases
Stomatognathic Diseases
Lip Diseases
Cisplatin
Antineoplastic Agents