The purpose of this study is to determine whether the combination of palbociclib with cetuximab is superior to cetuximab in prolonging overall survival in HPV-negative, cetuximab-naive patients with recurrent/metastatic squamous cell carcinoma of the head and neck.
Active, not recruiting
Phase 2
NCT ID: NCT02499120
ORG ID: A5481044
NCI ID: 2015-000515-41
Squamous Cell Carcinoma of the Head and Neck (SCCHN)
| Drug | Synonyms | Arms |
|---|---|---|
| palbociclib | IBRANCE, PD-0332991 | Palbociclib plus Cetuximab |
| Cetuximab | ERBITUX | Palbociclib plus Cetuximab, Placebo plus Cetuximab |
| Placebo | Placebo plus Cetuximab |
The purpose of this study is to determine whether the combination of palbociclib with
cetuximab is superior to cetuximab in prolonging overall survival in HPV-negative,
cetuximab-naive patients with recurrent/metastatic squamous cell carcinoma of the head and
neck.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Palbociclib plus Cetuximab | Experimental | Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle; in combination with Cetuximab, 400 mg/m2 initial dose as a 120-minute IV infusion followed by 250 mg/m2 weekly infused over 60 minutes. | palbociclib, Cetuximab |
| Placebo plus Cetuximab | Active Comparator | Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle; in combination with Cetuximab, 400 mg/m2 initial dose as a 120-minute IV infusion followed by 250 mg/m2 weekly infused over 60 minutes. | Cetuximab, Placebo |
Key Inclusion Criteria:
- Histologically or cytologically confirmed squamous cell carcinoma of the oral cavity,
oropharynx, hypopharynx or larynx, not amenable for salvage surgery or radiotherapy.
- Measurable disease as defined per RECIST v. 1.1. Tumor lesions previously irradiated
or subjected to other locoregional therapy will only be deemed measureable if disease
progression at the treated site after completion of therapy is clearly documented.
- HPV- negative SCCHN tumor as determined per institutional standard (eg, p16 IHC;
multiplex nucleic acid sequence based amplification [NASBA] or other polymerase chain
reaction [PCR]-based assays).
- Documented progressive disease according to RECIST v1.1 (Appendix 2) following
receipt of at least 2 cycles of one platinum-containing chemotherapy regimen
administered for R/M disease (min. 50 mg/m2 for cisplatin, minimum area under the
curve [AUC] > 4 for carboplatin).
- Availability of a tumor tissue specimen (ie, archived formalin fixed paraffin
embedded tissue [block preferred, or 15 unstained slides]), which will be used for
centralized, retrospective biomarker analysis. If archived tumor tissue is not
available, then a de novo biopsy will be required for patient participation.
Key Exclusion Criteria:
- Prior nasopharyngeal cancer, salivary gland or sinus tumors.
- More than one chemotherapeutic regimen given for R/M disease. Prior treatment with
immunotherapy is allowed.
- Known active uncontrolled or symptomatic central nervous system (CNS) metastases,
carcinomatous meningitis, or leptomeningeal disease as indicated by clinical
symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS
metastases or cord compression are eligible if they have been definitively treated
with local therapy (eg, radiotherapy, stereotactic surgery) and are clinically stable
off anticonvulsants and steroids for at least 4 weeks before randomization.
- Progressive disease within 3 months after completion of curatively intended treatment
for locoregionally advanced SCCHN.
- Difficulty swallowing capsules or requirement for a feeding tube.
- Prior use of cetuximab in the R/M disease treatment setting (except cetuximab during
curative radiotherapy)
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both
Overall Survival (OS)
Patient-Reported Outcome (PRO) measures, EORTC QLQ-C30, between the treatment arms
Progression-free survival measure of efficacy between the treatment arms
Correlations between baseline biomarker (eg, p16, Rb) expression in tumor tissue and clinical efficacy in both treatment arms
Steady state trough concentrations for palbociclib, and trough and maximum concentrations for cetuximab in patients with R/M SCCHN
Duration of response measure of efficacy between the treatment arms
Objective response measure of efficacy between the treatment arms
Patient-Reported Outcome (PRO) measures, EORTC QLQ-H&N35, between the treatment arms
palbociclib, cetuximab, human papillomavirus, squamous cell carcinoma, head and neck cancer
