This trial aims to directly compare a reduced radiation dose to the standard of care in HPVOPC for non-inferiority, thus allowing for direct comparison of outcomes between the two groups. The study hypothesis is that LRC and PFS at 3 years for reduced dose CRT are non-inferior to standard dose CRT.
Active, not recruiting
Phase 3
NCT ID: NCT01706939
ORG ID: GCO 12-1050
NCI ID: HS 12-00359
Squamous Cell Carcinomas
| Drug | Synonyms | Arms |
|---|
This trial aims to directly compare a reduced radiation dose to the standard of care in
HPVOPC for non-inferiority, thus allowing for direct comparison of outcomes between the two
groups. The study hypothesis is that LRC and PFS at 3 years for reduced dose CRT are
non-inferior to standard dose CRT.
This is a randomized Phase III study comparing two doses of definitive radiation therapy
given with induction and concurrent chemotherapy in HPV-positive oropharynx, unknown primary
or nasopharynx cancer. Eligible, consented and registered patients will receive three cycles
of Docetaxel Cisplatin and 5-FU (TPF) induction chemotherapy. After 3 cycles, the patients
will be assessed for clinical, radiographic and pathologic response to TPF. Patients with a
clinical or radiographic CR or PR will be randomized on the second phase of this study,
where patients will undergo a 2:1 randomization to reduced (5600 cGy) or standard (7000 cGy)
dose radiotherapy with weekly Carboplatin. Patients not meeting the response criteria will
be treated with standard dose CRT. Patients not completing 3 cycles TPF for reasons of
toxicity, progressive disease, choice, or other medical necessity will be treated with
standard dose CRT or surgery depending on their primary site and overall medical condition
and followed for survival. Toxicity will be assessed by Symptom scores, QOL and SAE
monitoring. The primary end point of the trial is equivalent local regional control and PFS
at 3 years. Patients will be followed for 5 years.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Reduced Dose Radiation | Experimental | Patients randomized to receive a reduced (5600 cGy) dose radiotherapy with weekly Carboplatin | |
| Standard Dose Radiation | Active Comparator | Patients randomized to receive a standard (7000 cGy) dose radiotherapy with carboplatin |
Inclusion Criteria:
- Participants must have histologically or cytologically confirmed squamous cell
carcinoma of the oropharynx, unknown primary, or nasopharynx that is HPV positive as
determined by PCR and p16 positive as determined by IHC. Tissue from the primary site
must be available for biomarker studies. PCR and IHC must be performed in the central
laboratory (Zhang, MSSM)
- Stage 3 or 4 disease without evidence of distant metastases.
- At least one clinically evaluable or uni- or bi-dimensionally measurable lesion by
RECIST 1.1 criteria.
- Age > 18 years.
- No previous surgery, radiation therapy or chemotherapy for SSCHN (other than biopsy
or tonsillectomy) is allowed at time of study entry.
- ECOG performance status of 0 or 1.
- No active alcohol addiction (as assessed by medical caregiver and defined as at least
6 months without activity).
- Participants must have adequate bone marrow, hepatic and renal functions as defined
in the protocol.
- Ability to understand and the willingness to sign a written informed consent
document.
- Patients with Gilbert's Disease and absent hepatic pathology by history and clinical
assessment maybe treated on study with bilirubins > the ULN for the institution if
other liver function studies are within the normal range
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
thereafter.
- Previous or current malignancies at other sites, with the exception of adequately
treated in situ carcinoma of the cervix, basal or squamous cell carcinoma of the
skin, thyroid cancer, or other cancer curatively treated by surgery and with no
current evidence of disease for at least 5 years.
- Symptomatic peripheral neuropathy grade 2 by NCI Common Terminology Criteria
(NCI-CTC) version 4.
- Symptomatic altered hearing > grade 2 by NCI-CTCv4 criteria.
- Other serious illnesses or medical conditions including but not limited to:
1. Unstable cardiac disease despite treatment, myocardial infarction within 6
months prior to study entry
2. History of significant neurologic or psychiatric disorders including dementia or
seizures
3. Active clinically significant uncontrolled infection
4. Active peptic ulcer disease defined as unhealed or clinically active
5. Hypercalcemia
6. Active drug addiction including alcohol, cocaine or intravenous drug use defined
as occurring within the 6 months preceding diagnosis
7. Chronic Obstructive Pulmonary Disease, defined as being associated with a
hospitalization for pneumonia or respiratory decompensation within 12 months of
diagnosis. This does not include obstruction from tumor
8. Autoimmune disease requiring therapy, prior organ transplant, or HIV infection
9. Interstitial lung disease
10. Hepatitis C (test required)
- 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 therapeutic drug trial within 30 days of study
entry.
- Active smoking within the past 20 years with a cumulative Pack Year history of > 20
Pack Years or active smoking (Defined as > 1 cigarette per day) within the last 2
years
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both
Progression Free Survival (PFS)
Rate of local-regional control
Overall Survival
Acute Toxicity of CRT
Biomarkers predictive of failure
Reduced radiotherapy
Randomization, Phase III
Reduced radiation therapy
head and neck
oropharynx
unknown primary (cervical lymph nodes)
nasopharynx primary
HPV
p16
