Description:
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.
Title
- Brief Title: De-intensification of Radiation and Chemotherapy for Low-Risk HPV-related Oropharyngeal SCC: Follow-up Study
- Official Title: De-intensification of Radiation and Chemotherapy for Low-Risk HPV-related Oropharyngeal Squamous Cell Carcinoma
Clinical Trial IDs
- ORG STUDY ID:
LCCC1413
- NCT ID:
NCT02281955
Conditions
- Carcinoma, Squamous Cell
- Head and Neck Neoplasms
- Oropharyngeal Neoplasms
Interventions
Drug | Synonyms | Arms |
---|
Cisplatin (or alternative) | | De-escalated Radiation and Chemotherapy |
Purpose
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.
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.
Trial Arms
Name | Type | Description | Interventions |
---|
De-escalated Radiation and Chemotherapy | Experimental | 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. | - Cisplatin (or alternative)
|
Eligibility 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
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | 2 Year Progression Free Survival After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC) |
Time Frame: | Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks) |
Safety Issue: | |
Description: | Progression Free Survival (PFS) was defined as the time from the beginning of treatment to cancer progression or death. The outcome measure will be reported as the proportion of patients with PFS at 2 years post-treatment. |
Secondary Outcome Measures
Measure: | 2 Year Local Control (LC) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC) |
Time Frame: | Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks). |
Safety Issue: | |
Description: | The outcome measure will be reported as the proportion of patients with LC at 2 years post-treatment. |
Measure: | 2 Year Regional Control (RC) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC) |
Time Frame: | Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks). |
Safety Issue: | |
Description: | The outcome measure will be reported as the proportion of patients with RC at 2 years post-treatment. |
Measure: | 2 Year Local-regional Control (LRC) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC) |
Time Frame: | Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks). |
Safety Issue: | |
Description: | The outcome measure will be reported as the proportion of patients with LRC at 2 years post-treatment. |
Measure: | 2 Year Distant Metastasis Free Survival (DMFS) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC) |
Time Frame: | Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks). |
Safety Issue: | |
Description: | The outcome measure will be reported as the proportion of patients with DMFS at 2 years post-treatment. |
Measure: | 2 Year Overall Survival (OS) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC) |
Time Frame: | Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks). |
Safety Issue: | |
Description: | The outcome measure will be reported as the proportion of patients who are still alive (overall survival) at 2 years post-treatment. |
Measure: | 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. |
Safety Issue: | |
Description: | |
Measure: | 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. |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | UNC Lineberger Comprehensive Cancer Center |
Trial Keywords
- Human Papillomavirus
- Oropharynx
- Oropharyngeal Squamous Cell Carcinoma
- Squamous Cell Carcinoma
- Radiation Therapy
- Chemotherapy
- p16
Last Updated
June 29, 2021