7H-14-1 An Open Label, Randomized Phase 3 Clinical Trial of Nivolumab vs Therapy of Investigator's Choice in Recurrent or Metastatic Platinum-refractory Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Head and neck carcinomas (HNC) describe cancers of the upper digestive tract which include squamous cell cancers (SCCHN) of the mouth, throat, and vocal chords. At present, there is no effective standard of care that provides survival benefits beyond 4 - 6 months in second line treatment of SCCHN that spreads or returns and does not respond to platinum treatment (refractory). Nivolumab is a drug that binds to a tumor cell receptor that blocks the immune system, thus allowing the immune system to attack tumor cells. Nivolumab has demonstrated clinical activity across several tumor types, but there has been no clinical trial so far to study the clinical benefit of nivolumab in SCCHN. Cetuximab, methotrexate, and docetaxel, which appear to be the most active in the platinum refractory setting, have approved indications as single agents for treating SCCHN and will be used as the Investigator's Choice in this study. The objective of this study is to compare progression free survival (PFS) and overall survival (OS) of Nivolumab to Investigators Choice in subjects who have tumor progression within 6 months of last dose of platinum therapy.
Patients who will be enrolled for this study will have laboratory confirmed SCCHN whose disease has spread or returned within 6 months of being treated with a platinum based therapy. Participants will be randomized to receive one of the following: nivolumab, cetuximab, methotrexate, or docetaxel. During the study, participants in all groups will have the study procedures done during each cycle as stated in the protocol. All participants will stop taking study drug(s) if their disease worsens, they have another illness which prevents them from taking the study drug(s), they cannot tolerate the side effects, they withdraw from the study, their study doctor thinks that being on the study is no longer in their best interest, or the sponsor stops the study. All participants will be followed for 35 days and 80 days after stopping the study drug(s), and then every 3 months until death.
Subject characteristics including demographics, baseline performance status, disease
characteristics and baseline laboratory parameters will be summarized by randomized treatment
arm, as well as pooled across randomized treatment arm. A two-sided 0.03 log-rank test will be used to do a formal comparison of PFS across all treatment arms. Median PFS will be estimated via the Kaplan-Meier product limit method. Two-sided 95% confidence intervals (CI) for the median PFS will be computed for each randomized arm. Kaplan-Meier plots of PFS will be presented. Hazard ratios (HR) and corresponding two-sided (1-adjusted )% CI will be estimated using a Cox proportional hazards model, with treatment arm as a single covariate, stratified by the above factor, corresponding to each comparison of PFS. OS will be compared between the treatment arms among all randomized subjects using a two sided, = 0.02 level log-rank test (adjusted for interim analysis), stratified using the same factor as in PFS.
Phase I/II Trial of Cediranib Alone or Cediranib and Lenalidomide in Iodine 131-Refractory Differentiated Thyroid Cancer
I. Determine the maximum tolerated dose (MTD) of cediranib (cediranib maleate) plus
lenalidomide. (Phase I) II. Determine the progression-free survival rates of single agent
cediranib in patients with iodine refractory, unresectable differentiated thyroid cancer
(DTC) who have evidence of disease progression within 12 months of study enrollment. (Phase
II) III. Determine the progression-free survival rates of cediranib in combination with
lenalidomide in patients with iodine refractory, unresectable DTC who have evidence of
disease progression within 12 months of study enrollment. (Phase II) IV. Compare the
progression-free survival curves of single agent cediranib to combination therapy with
cediranib with lenalidomide. (Phase II)
I. Determine the response rate of cediranib in combination with lenalidomide in patients
with iodine refractory, unresectable DTC who have evidence of disease progression within 12
months of study enrollment. (Phase I) II. Determine the toxicity, duration of response,
progression free survival, and overall survival in patients with DTC treated with cediranib
plus lenalidomide. (Phase I) III. Determine response rates and duration of response, early
tumor size changes, the toxicity, and overall survival in patients with DTC treated with
cediranib or cediranib plus lenalidomide. (Phase II) IV. Determine whether the presence of
v-raf murine sarcoma viral oncogene homolog B1 (B-RAF) or V-Ki-ras2 Kirsten rat sarcoma
(K-RAS) mutations in patients with DTC predict response to cediranib or cediranib plus
lenalidomide. (Phase II)
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
Phase I: Patients receive cediranib maleate orally (PO) once daily (QD) on days 1-28 and
lenalidomide PO QD on days 1-21 or 1-28. Courses repeat every 4 weeks in the absence of
disease progression or unacceptable toxicity.
Phase II: Patients are randomized to 1 of 2 treatment arms.
ARM A: Patients receive cediranib maleate PO QD on days 1-28. Courses repeat every 4 weeks
in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive cediranib maleate PO and lenalidomide PO as in Phase I.
After completion of study treatment, patients are followed up periodically.
Not recruiting | Head and Neck Cancers | Multisite
A Multicenter Trial of FDG-PET/CT Staging of Head and Neck Cancer and Its Impact on the N0 Neck Surgical Treatment in Head and Neck Cancer Patients
- Determine the negative predictive value of PET/CT imaging based upon pathologic
sampling of the neck lymph nodes in patients with head and neck cancer planning to
undergo N0 neck surgery.
- Determine the potential of PET/CT imaging to change treatment.
- Estimate the sensitivity and diagnostic yield of PET/CT imaging for detecting occult
metastasis in the clinical N0 neck (both by neck and lymph node regions) or other local
- Determine the effect of other factors (e.g., tumor size, location, secondary primary
tumors, or intensity of FDG uptake) that can lead to identification of subsets of
patients that could potentially forego neck dissection or that can provide preliminary
data for subsequent studies.
- Compare the cost-effectiveness of using PET/CT imaging for staging head and neck cancer
vs current good clinical practices.
- Evaluate the incidence of occult distant body metastasis discovered by whole-body
- Correlate PET/CT imaging findings with CT/MRI findings and biomarker results.
- Evaluate the quality of life of these patients, particularly of those patients whose
management could have been altered by imaging results.
- Evaluate PET/CT imaging and biomarker data for complementary contributions to
metastatic disease prediction.
- Compare baseline PET/CT imaging and biomarker data with 2-year follow up as an adjunct
assessment of their prediction of recurrence, disease-free survival, and overall
- Determine the proportion of neck dissections that are extended (i.e., additional levels
that clinicians intend to dissect beyond the initial surgery plan) based on
local-reader PET/CT imaging findings shared with the surgeon before dissection.
- Estimate the optimum cutoff value of standardized uptake values for diagnostic accuracy
of PET/CT imaging.
- Evaluate the impact of PET/CT imaging on the N0 neck across different tumor subsites
(defined by anatomic location).
OUTLINE: This is a multicenter study.
Patients undergo fludeoxyglucose F 18-PET/CT imaging. Approximately 14 days later, patients
undergo unilateral or bilateral neck dissection.
Patients complete quality-of-life questionnaires at baseline and at 1, 12, and 24 months
Patients undergo blood and tissue sample collection periodically for biomarker analysis.
Patients are followed up periodically for up to 2 years after surgery.
Not recruiting | Head and Neck Cancers | Multisite