Description:
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.
Title
- Brief Title: The Quarterback Trial: Reduced Dose Radiotherapy for HPV+ Oropharynx Cancer
- Official Title: The Quarterback Trial: A Randomized Phase III Clinical Trial Comparing Reduced and Standard Radiation Therapy Doses for Locally Advanced HPV Positive Oropharynx Cancer
Clinical Trial IDs
- ORG STUDY ID:
GCO 12-1050
- NCT ID:
NCT01706939
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Carboplatin | | Reduced Dose Radiation |
Purpose
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.
Detailed Description
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.
Trial Arms
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 | |
Eligibility Criteria
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Progression Free Survival (PFS) |
Time Frame: | at 3 years |
Safety Issue: | |
Description: | To determine the comparative rate of progression free survival (PFS) at 3 years in patients with advanced HPV related oropharynx cancer, nasopharynx cancer or unknown primary treated with reduced or standard dose radiation. |
Secondary Outcome Measures
Measure: | Rate of local-regional control |
Time Frame: | at 3 years |
Safety Issue: | |
Description: | To determine the comparative rate of local-regional control (LRC) at 3 years in patients with advanced HPV related oropharynx cancer or unknown primary treated with reduced or standard dose radiation. |
Measure: | Overall Survival |
Time Frame: | at 5 years |
Safety Issue: | |
Description: | To determine Overall Survival (OS) 5 years treated with reduced or standard dose CRT. |
Measure: | Acute Toxicity of CRT |
Time Frame: | at 5 years |
Safety Issue: | |
Description: | To compare acute toxicity in patients treated with reduced or standard dose CRT. |
Measure: | Biomarkers predictive of failure |
Time Frame: | at 5 years |
Safety Issue: | |
Description: | To determine biomarkers predictive of failure with either reduced or standard dose radiotherapy. |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Icahn School of Medicine at Mount Sinai |
Trial Keywords
- Reduced radiotherapy
- Randomization, Phase III
- Reduced radiation therapy
- head and neck
- oropharynx
- unknown primary (cervical lymph nodes)
- nasopharynx primary
- HPV
- p16
Last Updated
January 28, 2021