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De-intensification of Radiation and Chemotherapy for Low-Risk HPV-related Oropharyngeal SCC: Follow-up Study

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ClinicalTrials.gov Identifier: NCT02281955
Recruitment Status : Active, not recruiting
First Posted : November 4, 2014
Last Update Posted : May 18, 2018
Sponsor:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center

Brief Summary:
The purpose of this research study is to learn about the effectiveness of using lower-intensity radiation and chemotherapy to treat human papillomavirus (HPV) associated low-risk oropharyngeal and/or unknown primary squamous cell carcinomas of the head and neck. The cure rate for this type of cancer is estimated to be high, > 90%. The standard treatment for this cancer is 7 weeks of radiation with 3 high doses of cisplatin. Sometimes surgery is performed afterwards. This standard regimen causes a lot of side effects and long term complications. This study is evaluating whether a lower dose of radiation and chemotherapy may provide a similar cure rate as the longer, more intensive standard regimen. Patients in this study will receive 1 less week of radiation and a lower weekly dose of chemotherapy.

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

Detailed Description:
The proposed study is a follow-up study to NCT01530997. In NCT01530997, patients with HPV positive and/or p16 positive low-risk oropharyngeal squamous cell carcinoma (OPSCC) received de-intensified chemoradiotherapy (CRT) followed by a limited surgical evaluation. The primary endpoint of NCT01530997 was the rate of pathological complete response (pCR) after CRT. Power computations were performed for N=40 and were based on the null hypothesis (H0) that the pCR for de-intensified chemoradiotherapy is at least 87%, the historical rate. The type 1 error for this calculation was 14.2%. 43 patients enrolled and 38 were evaluable for the primary endpoint. The observed pCR rate was 89% (34/38). Since the observed pCR rate was excellent in NCT01530997 and was in concordance with the expected rate, in the proposed study we will not mandate a post-CRT surgical evaluation. Instead a PET/CT 10 to 16 weeks post-CRT will be used to determine whether a surgical evaluation is needed.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 115 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: De-intensification of Radiation and Chemotherapy for Low-Risk HPV-related Oropharyngeal Squamous Cell Carcinoma
Actual Study Start Date : August 2014
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : November 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Cisplatin

Arm Intervention/treatment
Experimental: De-escalated Radiation and Chemotherapy
Patients will receive Intensity Modulated Radiotherapy Treatments (IMRT), 60 Gy at 2 Gy/fx. 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. Chemotherapy will not be given to patients with T0-2 N0-1 disease, ≤ 10 pack years smoking history. 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.
Radiation: Intensity Modulated Radiotherapy (IMRT)
All patients will receive Intensity Modulated Radiotherapy Treatments (IMRT). Dose painting IMRT will be used and all doses will be specified to the planning target volume (PTV). The high risk planning target volume (PTV-HR) and standard risk planning target volume (PTV-SR) will be treated to the following respective total doses: 60 Gy and 54 Gy. The dose per fraction to the PTV-HR and PTV-SR will be 2 Gy per day and 1.8 Gy per day respectively. The PTV-HR will include the gross tumor and the PTV-SR will include areas at risk for harboring subclinical microscopic disease.

Drug: Cisplatin (or alternative)
Cisplatin is the preferred mandated first choice chemotherapy, however alternative weekly regimens are permissible. Justification for not using cisplatin must be documented. Chemotherapy will be given intravenously weekly during IMRT. 6 total doses will be given. It is preferred that the doses be administered on days 1, 8, 15, 22, 29, and 36; however, this is not mandatory. Chemotherapy will not be given to patients with T0-2 N0-1 disease, ≤ 10 pack years smoking history.

Procedure: Assessment for surgical evaluation
Decisions for surgical evaluation will be based on the results of the PET/CT 10 to 16 weeks after CRT and clinical exam (including fiberoptic laryngoscopy) at that time. Other optional imaging studies may be performed. Patients with a positive PET/CT scan will undergo surgical evaluation at the discretion of the surgeon, with the goal being to remove any suspected residual tumor with a negative resection margin while maintaining organ preservation. This may include biopsies and/or oncological resections of the primary tumor and lymph node metastases. Patients with a negative PET/CT scan will be observed.




Primary Outcome Measures :
  1. 2 year Progression Free Survival after de-intensified CRT in HPV-positive and/or p16 positive low-risk OPSCC [ Time Frame: Two years after completion of CRT on last enrolled patient ]

Secondary Outcome Measures :
  1. Local control rate [ Time Frame: 2 years post-CRT ]
  2. Regional control rate [ Time Frame: 2 years post-CRT ]
  3. Local-regional control rate [ Time Frame: 2 years post-CRT ]
  4. Distant metastasis free survival [ Time Frame: 2 years post-CRT ]
  5. Overall survival rate [ Time Frame: 2 years post-CRT ]
  6. Head and neck quality of life assessments [ Time Frame: Within 2 weeks prior to CRT, weekly during CRT, 10-16 weeks after CRT, follow-up visits every 2 months after CRT for 2 years, then every 6 months for 3 years, then yearly, up to 10 years. ]
  7. Speech and swallowing function [ Time Frame: Within 2 weeks prior to CRT, 6-8 weeks after CRT, 6 months after CRT (MBS); Within 2 weeks prior to CRT, 10-16 weeks after CRT, follow-up visits every 2 months after CRT for 2 years, then every 6 months for 3 years, then yearly (EAT-10), up to 10 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. ≤ 10 pack-years smoking history or ≤ 30 pack-years smoking history WITH ≥ 5 years abstinence from smoking
  5. Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks prior to treatment
  6. ECOG Performance Status 0-1
  7. 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.
  8. Adequate renal and hepatic function within 4 weeks prior to registration, defined as follows: Serum creatinine < 2.0 mg/dl; Total bilirubin < 2 x the institutional ULN; AST or ALT < 3 x the institutional ULN.
  9. Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential
  10. Women of childbearing potential and male participants who are sexually active must practice adequate contraception during treatment and for 6 weeks following treatment.
  11. Patients must be deemed able to comply with the treatment plan and follow-up schedule.
  12. 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 radiographgically 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): NCT02281955


Locations
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
United States, North Carolina
University of North Carolina at Chapel Hill, Department of Radiation Oncology
Chapel Hill, North Carolina, United States, 27599
Pardee Memorial Hospital
Hendersonville, North Carolina, United States, 28791
High Point Regional Health
High Point, North Carolina, United States, 27262
Rex Healthcare
Raleigh, North Carolina, United States, 27607
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Investigators
Principal Investigator: Bhishamjit Chera, MD University of North Carolina at Chapel Hill, Department of Radiation Oncology

Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT02281955     History of Changes
Other Study ID Numbers: LCCC1413
First Posted: November 4, 2014    Key Record Dates
Last Update Posted: May 18, 2018
Last Verified: May 2018

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:
Carcinoma
Neoplasms
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Oropharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Neoplasms by Site
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Cisplatin
Antineoplastic Agents