Human Papilloma Virus, Squamous Cell Carcinoma of the Head and Neck
Conditions
Keywords
SSCHN, HPV, IMRT
Brief summary
In this research study, the investigators are studying whether a reduced dose of radiation when given with standard doses of chemotherapy can reduce side effects without compromising control of the cancer. An approved treatment for squamous cell carcinoma of the head and neck is initial chemotherapy followed by radiation and chemotherapy together. This treatment is effective but has many immediate and long-term side effects. People who have squamous cell carcinoma of the head and neck (SSCHN) that is related to an infection by the human papillomavirus (HPV) have been shown to have a high response to this treatment along with a high cure rate. The investigators think that by reducing the intensity of this treatment, they may be able to reduce immediate and long-term side effects which may lead to long term improvements in quality of life and function.
Detailed description
OBJECTIVES: Primary To determine rate of local-regional control at 2 years Secondary To determine Progression Free Survival at 2 and 5 years To determine Overall Survival at 2 and 5 years To assess acute toxicity and long term toxicity of reduced radiation dose at 2 and 5 years
Interventions
DRUGdocetaxel
DRUGcisplatin
Given intravenously on day 1 of each cycle
DRUG5-FU
RADIATIONIMRT
DRUGcetuximab
DRUGcarboplatin
Sponsors
Dana-Farber Cancer Institute
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
* Histologically or cytologically confirmed squamous cell carcinoma of the oropharynx or unknown primary that is HPV 16 positive as determined by ISH and p16 positive as determined by IHC. * Stage 3 or 4 disease without evidence of distant metastases * At least one evaluable or uni- or bi-dimensionally measurable lesion by RECIST 1.1 criteria * 18 years of age or older * No previous surgery, radiation therapy or chemotherapy for SSCHN is allowed at time of study entry * ECOG Performance Status of 0 or 1 * No active alcohol addiction * Adequate bone marrow, hepatic and renal function as defined in the protocol * Women of child-bearing potential must have a negative pregnancy test within 7 days of starting treatment
Exclusion criteria
* Pregnant or breast feeding women or women and men of childbearing potential not willing to use adequate contraception while on treatment and for at least 3 months after * Previous or current malignancies at other sites * Symptomatic peripheral neuropathy of grade 2 or greater * Symptomatic altered hearing greater than grade 2 * Other serious illnesses or medical conditions * Patients that have experienced an involuntary weight loss of more than 25% of their body weight in the 2 months preceding study entry * Concurrent treatment with any other anticancer therapy * Participation in an investigational trial within 30 days of study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2-Year Local-Regional Control Rate | Follow-up for response continued until first progression. Disease assessments occurred at completion of induction cycle 3 along with months 12, 18 and 24 post study registration. | 2-year local-regional control rate is defined as the proportion of participants who achieve confirmed stable disease (SD) or better by 2-years post study registration based on RECIST 1.0 criteria. Per RECIST 1.0 for target lesions, complete response (CR) is disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. Progressive disease (PD) is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started. SD is neither PR nor PD. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 4-y Overall Survival Rate | Patients were followed for survival up to 5 years from study entry. Patients alive have been followed for a mean of 55 months (range 52-60 months). | 4-year overall survival rate is the percentage of patients remaining alive 4-years from study entry. |
Countries
United States
Participant flow
Recruitment details
7 participants were enrolled between July 2011 and May 2012.
Participants by arm
| Arm | Count |
|---|---|
| TPF Induction Chemotherapy Followed by Chemoradiotherapy Patients received 3 cycles (21 days each) of TPF induction chemotherapy: docetaxel 75 mg/m2 IV day 1; cisplatin 100 mg/m2 IV day 1 (carboplatin substitute permitted); 5-FU 1000 mg/m2/day IV pump continuous days 1-4. Concurrent chemoradiotherapy followed 4-6 weeks after day 1 of cycle 3 TPF induction: cetuximab 400 mg/m2 IV loading dose 1 week prior and 250 mg/m2 IV weekly (panitumumab substitute permitted); carboplatin AUC 1.5 (Calvert formula) IV weekly; Intensity modulated radiation therapy (IMRT)-response based dosing for 6-7 weeks. | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | TPF Induction Chemotherapy Followed by Chemoradiotherapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 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 | 1 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
2-Year Local-Regional Control Rate
2-year local-regional control rate is defined as the proportion of participants who achieve confirmed stable disease (SD) or better by 2-years post study registration based on RECIST 1.0 criteria. Per RECIST 1.0 for target lesions, complete response (CR) is disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. Progressive disease (PD) is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started. SD is neither PR nor PD. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time frame: Follow-up for response continued until first progression. Disease assessments occurred at completion of induction cycle 3 along with months 12, 18 and 24 post study registration.
Population: The study was terminated early due to weak accrual. Clinical outcome data were not accessible for results reporting due to the designation of study completed at the institution.
Secondary
4-y Overall Survival Rate
4-year overall survival rate is the percentage of patients remaining alive 4-years from study entry.
Time frame: Patients were followed for survival up to 5 years from study entry. Patients alive have been followed for a mean of 55 months (range 52-60 months).
Population: The analysis dataset is comprised of all treated patients. Since all patients have not been followed for survival for 5 years the 4-year rate is provided. All data provided was based on chart review and not from case report forms.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TPF Induction Chemotherapy Followed by Chemoradiotherapy | 4-y Overall Survival Rate | 100 percentage of participants |