Head and Neck Cancer
Conditions
Keywords
Human Papillomavirus, HPV
Brief summary
The purpose of this study is to determine whether human papillomavirus (HPV)-positive head and neck cancer can be treated with a less aggressive regimen of radiation therapy and chemotherapy (paclitaxel) after initially receiving two cycles of chemotherapy (carboplatin/paclitaxel).
Detailed description
Given the toxicity of high dose cisplatin, attention has focused on identifying patients at lower risk for failure who may potentially benefit from less aggressive chemoradiotherapy approaches. HPV-positive Head and Neck Cancer responds favorably to radiation therapy. This has prompted investigators to suggest that patients with these cancers might be over-treated and unnecessarily subjected to the toxicity of intensive chemoradiotherapy with excessively high radiation doses. This study will select patients with HPV-positive Head and Neck cancer for attenuated therapy and may have important implications for individualization of care in the future. The regimen of carboplatin and paclitaxel was selected for the induction chemotherapy phase because of its ease of administration, improved toxicity profile, high rates of dose delivery, and excellent published results showing high response rates and overall survival. This study will use induction chemotherapy primarily as a means to select HPV-positive Head and Neck Cancer patients, who may benefit from significant radiation dose de-intensification in the concurrent chemoradiotherapy phase of treatment. The rationale for this risk-adapted approach to local therapy based on HPV status is to administer effective comprehensive treatment individualized at diagnosis and after assessment of response to induction chemotherapy (for patients with HPV-positive tumors), thus avoiding unnecessary and potentially toxic treatment, and hence optimizing the therapeutic ratio.
Interventions
RADIATIONInduction Chemotherapy followed by Response Adapted Chemoradiation
All patients receive induction chemotherapy with 2 cycles of paclitaxel and carboplatin followed by response adapted, de-escalated chemoradiation. Patients with a complete or partial response will receive 54 Gy with concurrent paclitaxel and patients with stable disease will receive 60 Gy with concurrent paclitaxel.
Sponsors
University of California, Davis
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically proven diagnosis of HPV-positive squamous cell carcinoma of the oropharynx, hypopharynx, or larynx. HPV-positivity will be defined as tumors that are p16-positive by immunohistochemistry. * Clinical stage III or IV disease; Note: Patients with M1 tumors are not eligible. * Appropriate stage for protocol entry, including no distant metastases, based upon minimum diagnostic workup * Zubrod Performance Status 0-1 * Age \> 18 * Adequate bone marrow function * Adequate hepatic function * Adequate renal function * Pregnancy test within 4 weeks prior to registration for women of childbearing potential * Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study (until at least 60 days following the last study treatment) * Patient must sign study specific informed consent prior to study entry.
Exclusion criteria
* Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; * Patients with simultaneous primaries or bilateral tumors are excluded. * Patients who present with a cervical lymph node metastasis of unknown primary origin; * Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable; * Prior radiotherapy that would result in overlap of radiation therapy fields; * Primary site of tumor of oral cavity, nasopharynx, nasal cavity, paranasal sinuses, or salivary glands; * Recurrent head and neck cancer; * Severe, active co-morbidity * Pregnant or lactating women or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic. * Prior allergic reaction to the study drug(s) involved in this protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Progression-free Survival | Up to 2 years | Defined from date of registration to date of first documentation of progression and/or distant metastasis, or death due to any cause. The true 2-year progression-free survival rate will be estimated by the proportion of efficacy-evaluable patients on study without documentation of disease progression or death 2 years from registration. A 95% confidence interval (CI) for the true progression-free survival rate will be constructed using the Duffy-Santner approach. However, Kaplan-Meier methodology will be used to estimate the final 2-year progression-free survival rate and its 95% CI in case there are censored patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Overall Survival | Up to 5 years | Defined as the time from registration to death using the Kaplan-Meier method.. |
| Number of Patients With Toxicity of Concurrent Chemoradiotherapy | Up to 5 years | Assessed by NCI Common Toxicity Criteria for Adverse Effects, Version 4.0. Reported participants who experienced an AE during concurrent chemoradiotherapy. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Response Adapted Chemoradiation Paclitaxel 175 mg/m2 + Carboplatin area under curve (AUC) 6 followed by response adapted Radiation Therapy (5 - 6 weeks) + Paclitaxel
Induction Chemotherapy followed by Response Adapted Chemoradiation: All patients receive induction chemotherapy with 2 cycles of paclitaxel and carboplatin followed by response adapted, de-escalated chemoradiation. Patients with a complete or partial response will receive 54 Gy with concurrent paclitaxel and patients with stable disease will receive 60 Gy with concurrent paclitaxel. | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | Response Adapted Chemoradiation |
|---|---|
| Age, Continuous | 63.1 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 18 |
| other Total, other adverse events | 13 / 18 |
| serious Total, serious adverse events | 2 / 18 |
Outcome results
Primary
Number of Participants With Progression-free Survival
Defined from date of registration to date of first documentation of progression and/or distant metastasis, or death due to any cause. The true 2-year progression-free survival rate will be estimated by the proportion of efficacy-evaluable patients on study without documentation of disease progression or death 2 years from registration. A 95% confidence interval (CI) for the true progression-free survival rate will be constructed using the Duffy-Santner approach. However, Kaplan-Meier methodology will be used to estimate the final 2-year progression-free survival rate and its 95% CI in case there are censored patients.
Time frame: Up to 2 years
Population: One subject withdrew consent prior to completing study
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Response Adapted Chemoradiation | Number of Participants With Progression-free Survival | 17 Participants |
Secondary
Number of Participants With Overall Survival
Defined as the time from registration to death using the Kaplan-Meier method..
Time frame: Up to 5 years
Population: One subject withdrew consent prior to completing study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Response Adapted Chemoradiation | Number of Participants With Overall Survival | 16 Participants |
Secondary
Number of Patients With Toxicity of Concurrent Chemoradiotherapy
Assessed by NCI Common Toxicity Criteria for Adverse Effects, Version 4.0. Reported participants who experienced an AE during concurrent chemoradiotherapy.
Time frame: Up to 5 years
Population: One subject withdrew consent prior to completing study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Response Adapted Chemoradiation | Number of Patients With Toxicity of Concurrent Chemoradiotherapy | 17 Participants |