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P53 Mutational Status and cf HPV DNA for the Management of HPV-associated OPSCC

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ClinicalTrials.gov Identifier: NCT03077243
Recruitment Status : Recruiting
First Posted : March 10, 2017
Last Update Posted : August 28, 2019
Sponsor:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center

Brief Summary:
The primary objective of this study is to evaluate whether genomic based risk-stratification can be used in deciding whether to de-intensify in patients with Human Papillomavirus (HPV)-associated Oropharyngeal Squamous Cell Carcinoma (OPSCC) with > 10 pack years smoking history. Hypothesis: Patients with HPV-associated OPSCC, > 10 pack years smoking history, and non-mutated p53 will have similar 2 year progression-free survival (PFS) as patients with < 10 pack years smoking history.

Condition or disease Intervention/treatment Phase
Carcinoma, Squamous Cell Head and Neck Neoplasms Oropharyngeal Neoplasms Radiation: Intensity Modulated Radiotherapy (IMRT) - deintensified Radiation: Intensity Modulated Radiotherapy (IMRT) - standard Drug: Cisplatin (or alternative) - deintensified Drug: Cisplatin (or alternative) - standard Procedure: Assessment for surgical evaluation Phase 2

Detailed Description:
The proposed study is a follow-up study to LCCC 1120 and 1413. The investigators have shown that de-intensification is efficacious in these two phase II studies. A major question is whether the investigators can de-intensify in patients with HPV-associated oropharyngeal cancer who have smoking histories. The investigators' hypothesis is that genomic profiling of patients' tumors (specifically for p53 mutations) will help in triaging patients to de-intensification versus standard of care. Patients with HPV-associated OPSCC will be enrolled regardless of smoking history and p53 mutational status will be assessed in patients with a smoking history. The investigators will use the same de-intensification chemoradiotherapy regimen already evaluated in LCCC 1120 and 1413 in patients with HPV-associated OPSCC who have a minimal smoking history and in patients with a smoking history but with wild-type p53. Patients with a smoking history who have mutated p53 will not receive de-intensified chemoradiotherapy, but instead will receive standard doses. The hypothesis is that by using genomics in the patients with a significant smoking history, the investigators will better select those who can be safely de-intensified. Circulating free HPV DNA (cf-HPV-DNA) will also be prospectively assessed from blood samples.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: LCCC 1612: P53 Mutational Status and Circulating Free HPV DNA for the Management of HPV-associated Oropharyngeal Squamous Cell Cancers
Actual Study Start Date : December 2016
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : February 2025

Arm Intervention/treatment
Experimental: ≤ 10 pack years smoking history Radiation: Intensity Modulated Radiotherapy (IMRT) - deintensified
60 Gy at 2 Gy/fx

Drug: Cisplatin (or alternative) - deintensified
The acceptable weekly chemotherapy regimens are Cisplatin 30 to 40 mg/m2 (first choice), Cetuximab 250mg/m2 (second choice), Carboplatin AUC 1.5 and paclitaxel 45 mg/m2 (third choice), Carboplatin AUC 3 (fourth choice). Chemotherapy will be given intravenously weekly during IMRT, 6 total doses.

Procedure: Assessment for surgical evaluation
Decision for surgical evaluation will be based on the results of the PET/CT and clinical exam 10-16 weeks after CRT. Patients with a positive PET/CT scan will undergo surgical evaluation at the discretion of the surgeon. Patients with a negative PET/CT scan will be observed.

Experimental: > 10 py smoking history, no p53 mutation Radiation: Intensity Modulated Radiotherapy (IMRT) - deintensified
60 Gy at 2 Gy/fx

Drug: Cisplatin (or alternative) - deintensified
The acceptable weekly chemotherapy regimens are Cisplatin 30 to 40 mg/m2 (first choice), Cetuximab 250mg/m2 (second choice), Carboplatin AUC 1.5 and paclitaxel 45 mg/m2 (third choice), Carboplatin AUC 3 (fourth choice). Chemotherapy will be given intravenously weekly during IMRT, 6 total doses.

Procedure: Assessment for surgical evaluation
Decision for surgical evaluation will be based on the results of the PET/CT and clinical exam 10-16 weeks after CRT. Patients with a positive PET/CT scan will undergo surgical evaluation at the discretion of the surgeon. Patients with a negative PET/CT scan will be observed.

Active Comparator: > 10 py smoking history, p53 mutation Radiation: Intensity Modulated Radiotherapy (IMRT) - standard
70 Gy at 2 Gy/fx

Drug: Cisplatin (or alternative) - standard
The acceptable weekly chemotherapy regimens are Cisplatin 30 to 40 mg/m2 (first choice), Cetuximab 250mg/m2 (second choice), Carboplatin AUC 1.5 and paclitaxel 45 mg/m2 (third choice), Carboplatin AUC 3 (fourth choice). Chemotherapy will be given intravenously weekly during IMRT, 7 total doses.

Procedure: Assessment for surgical evaluation
Decision for surgical evaluation will be based on the results of the PET/CT and clinical exam 10-16 weeks after CRT. Patients with a positive PET/CT scan will undergo surgical evaluation at the discretion of the surgeon. Patients with a negative PET/CT scan will be observed.




Primary Outcome Measures :
  1. 2 year Progression Free Survival after de-intensified chemoradiation therapy (CRT) in HPV-associated OPSCC [ Time Frame: Two years after completion of CRT on last enrolled patient ]

Secondary Outcome Measures :
  1. Changes in plasma circulating free HPV DNA during and after treatment as related to clinical outcomes in patients with HPV-associated OPSCC [ Time Frame: Two years after completion of CRT on last enrolled patient ]
  2. Local control rate [ Time Frame: 2 years post-CRT ]
  3. Regional control rate [ Time Frame: 2 years post-CRT ]
  4. Local-regional control rate [ Time Frame: 2 years post-CRT ]
  5. Distant metastasis free survival [ Time Frame: 2 years post-CRT ]
  6. Overall survival rate [ Time Frame: 2 years post-CRT ]
  7. Head and neck quality of life assessments [ Time Frame: From date of study enrollment to last follow-up as long as patient continues seeing study doctor, up to 30 years ]
  8. Speech and swallowing function via penetration-aspiration scale (PAS) and EAT-10 survey assessments [ Time Frame: From date of study enrollment to last follow-up as long as patient continues seeing study doctor, up to 30 years ]


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

Inclusion Criteria:

  1. ≥ 18 years of age (no upper age limit)
  2. T0-3, N0 to N2c, M0 squamous cell carcinoma of the oropharynx
  3. Biopsy proven squamous cell carcinoma that is HPV and/or p16 positive
  4. Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks prior to treatment
  5. ECOG Performance Status 0-1
  6. CBC/differential obtained within 8 weeks prior to treatment, with adequate bone marrow function defined as follows: Platelets ≥ 100,000 cells/mm3; Hemoglobin ≥ 8.0 g/dl
  7. Adequate renal and hepatic function within 4 weeks prior to treatment, defined as follows: Serum creatinine < 2.0 mg/dl; Total bilirubin < 2 x the institutional ULN; AST or ALT < 3 x the institutional ULN
  8. Negative pregnancy test within 2 weeks prior to treatment for women of childbearing potential
  9. Women of childbearing potential and male participants who are sexually active must practice adequate contraception during treatment and for 6 weeks following treatment.
  10. Patients must be deemed able to comply with the treatment plan and follow-up schedule.
  11. Patients must provide study specific informed consent prior to study entry

Exclusion Criteria:

  1. Prior history of radiation therapy to the head and neck
  2. Prior history of head and neck cancer.
  3. Unresectable disease (e.g. immobile node on physical exam, nodal disease that radiographically involves the carotid arteries, nerves)
  4. Currently taking Disease Modifying Rheumatoid Drugs (DMRDs)
  5. Severe, active co-morbidity, defined as follows: Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months; Transmural myocardial infarction within the last 6 months; Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration; Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects (Note, however, coagulation parameters are not required for entry into this protocol); Pre-existing ≥ grade 2 neuropathy; Prior organ transplant; Systemic lupus; Psoriatic arthritis
  6. Known HIV positive.

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): NCT03077243


Contacts
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Contact: Bhishamjit Chera, MD (984) 974-0400 bchera@med.unc.edu
Contact: Rebecca Green, MSW (984) 974-8440 rlgreen@med.unc.edu

Locations
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United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32610
Contact: Robert Amdur, MD    352-265-0287    amdurr@shands.ufl.edu   
University of Florida Proton Therapy Institute Recruiting
Jacksonville, Florida, United States, 32206
Contact: Roi Dagan, MD    904-588-1445    rdagan@floridaproton.org   
United States, North Carolina
University of North Carolina at Chapel Hill, Department of Radiation Oncology Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Bhishamjit Chera, MD    984-974-0400    bchera@med.unc.edu   
Contact: Rebecca Green, MSW    (984) 974-8440    rlgreen@med.unc.edu   
Rex Healthcare Recruiting
Raleigh, North Carolina, United States, 27607
Contact: Nathan Sheets, MD    919-784-1251    nathan.sheets@unchealth.unc.edu   
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Investigators
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Principal Investigator: Bhishamjit Chera, MD University of North Carolina at Chapel Hill, Department of Radiation Oncology

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Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT03077243     History of Changes
Other Study ID Numbers: LCCC 1612
First Posted: March 10, 2017    Key Record Dates
Last Update Posted: August 28, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by UNC Lineberger Comprehensive Cancer Center:
Human Papillomavirus
Oropharynx
Oropharyngeal Squamous Cell Carcinoma
Squamous Cell Carcinoma
Radiation Therapy
Chemotherapy
p16
Additional relevant MeSH terms:
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Carcinoma
Head and Neck Neoplasms
Carcinoma, Squamous Cell
Oropharyngeal Neoplasms
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Squamous Cell
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Cisplatin
Antineoplastic Agents