A RANDOMIZED, MULTICENTER, DOUBLE-BLIND PHASE 2 STUDY OF PALBOCICLIB PLUS CETUXIMAB VERSUS CETUXIMAB FOR THE TREATMENT OF HUMAN PAPILLOMAVIRUS-NEGATIVE, CETUXIMAB-NAÏVE PATIENTS WITH RECURRENT/METASTATIC SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK AFTER FAILURE OF ONE PRIOR PLATINUM-CONTAINING CHEMOTHERAPY REGIMEN

• Register: EUCTR
• Last refreshed on: 23 October 2017
• Main ID: EUCTR2015-000515-41-HU
• Date of registration: 16/07/2015
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc, 235 East 42nd Street, New York, NY 10017
• Public title: A RANDOMIZED, MULTICENTER, DOUBLE-BLIND PHASE 2 STUDY OF PALBOCICLIB PLUS CETUXIMAB VERSUS CETUXIMAB FOR THE TREATMENT OF HUMAN PAPILLOMAVIRUS-NEGATIVE, CETUXIMAB-NAÏVE PATIENTS WITH RECURRENT/METASTATIC SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK AFTER FAILURE OF ONE PRIOR PLATINUM-CONTAINING CHEMOTHERAPY REGIMEN
• Scientific title: A RANDOMIZED, MULTICENTER, DOUBLE-BLIND PHASE 2 STUDY OF PALBOCICLIB PLUS CETUXIMAB VERSUS CETUXIMAB FOR THE TREATMENT OF HUMAN PAPILLOMAVIRUS-NEGATIVE, CETUXIMAB-NAÏVE PATIENTS WITH RECURRENT/METASTATIC SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK AFTER FAILURE OF ONE PRIOR PLATINUM-CONTAINING CHEMOTHERAPY REGIMEN
• Date of first enrolment: 25/08/2015
• Target sample size: 120
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000515-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, Hungary, Italy, Japan, Korea, Republic of, Mexico, Poland, Romania, Russian Federation, Serbia, Slovakia, Spain, Taiwan, Ukraine, United States

Contacts

• Name: ClinicalTrials.gov Call Center
• Affiliation: Pfizer Inc

• Name: ClinicalTrials.gov Call Center
• Affiliation: Pfizer Inc

Key inclusion & exclusion criteria

Inclusion criteria:
1. Histologically or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, not amenable for salvage surgery or radiotherapy.
2. Measuarable 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.
3. 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).
4. Documented progressive disease according to RECIST v1.1 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).
5. 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.
6. ECOG performance status (PS) 0 or 1.
7. Adequate organ and marrow function defined as follows:
- Leukocytes >3,000/mm3 (3.0 x 1.000.000.000/L);
- Absolute Neutrophil count (ANC) = 1,200/mm3 (1.2 x 1.000.000.000/L);
- Platelets = 75,000/mm3 (75 x 1.000.000.000/L);
- Hemoglobin (Hb) = 9 g/dL (90 g/L);
- Serum creatinine = 1.5 x upper limit of normal (ULN) or estimated creatinine clearance = 40 mL/min as calculated using the method standard for the institution;
- Total serum bilirubin = 1.5 x ULN (= 3.0 x ULN if Gilbert’s disease);
- Asparate aminotransferase (AST) and/or alanine aminotransferase (ALT) = 2 x ULN (= 5.0 x ULN if liver metastases present);
- Alkaline phosphatase = 2.5 x ULN (= 5.0 x ULN if bone or liver metastases present).
8. Male and female patients of childbearing potential and at risk for pregnancy must agree to use two highly effective methods of contraception throughout the study and for 6 months after the last dose of cetuximab.
Female subjects who are not of childbearing potential (ie, meet at least 1 of the following criteria):
- Have undergone a documented hysterectomy and/or bilateral oophorectomy;
- Have medically confirmed ovarian failure; or
- Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed by having a serum follicle stimulating hormone (FSH) level within the laboratory’s reference range for postmenopausal women.
9. Age = 18 years (or = 20 years as applicable by local country regulations).
10. Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
11. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 96
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 24

Exclusion criteria:
1. Prior nasopharyngeal cancer, salivary gland or sinus tumors.
2. More than one chemotherapeutic regimen given for R/M disease. Prior treatment with immunotherapy is allowed.
3. 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.
4. Progressive disease within 3 months after completion of curatively intended treatment for locoregionally advanced SCCHN.
5. Inability to swallow capsules..
6. Prior use of cetuximab in the R/M disease treatment setting.
7. Prior treatment with any CDK4/6 or EGFR inhibitor (except cetuximab during curative radiotherapy).
8. Patients treated within the last 7 days prior to randomization with:
- Food or drugs that are known to be strong CYP (cytochrome P-450) 3A4 inhibitors (ie, amprenavir, atazanavir, boceprevir, clarithromycin, conivaptan, delavirdine, diltiazem, erythromycin, fosamprenavir, indinavir, itraconazole, ketoconazole, lopinavir, mibefradil, miconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, verapamil, voriconazole, and grapefruit or grapefruit juice);
- Drugs that are known to be strong CYP3A4 inducers (ie, carbamazepine, felbamate, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentin, and St. John’s wort);
- Drugs that are known to prolong the QT interval.
9. Major surgery, chemotherapy, radiotherapy, any investigational agents, or other anti-cancer therapy within 2 weeks before randomization. Patients who received prior radiotherapy to = 25% of bone marrow are not eligible independent of when it was received.
10. Diagnosis of any other malignancy within 3 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
11. QTc >480 msec (based on the mean value of the triplicate electrocardiograms (ECGs), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes.
12. Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug (eg, hypocalcemia, hypokalemia, hypomagnesemia.
13. Any of the following within 6 months of randomization: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE version 4.03 Grade = 2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism.
14. Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or any upper gastrointestinal surgery including gastric resection that could impair drug absorption.
15. Known human immunodeficiency virus infection.
16. Other severe acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational product
administration or may interfere with the interpretation of study results and, in

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

RECURRENT/METASTATIC SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK
MedDRA version: 20.0 Level: PT Classification code 10063569 Term: Metastatic squamous cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: Palbociclib
Product Code: PD-0332991
Pharmaceutical Form: Capsule
INN or Proposed INN: Palbociclib
CAS Number: 571190-30-2
Current Sponsor code: PD-0332991
Other descriptive name: PD-332,991
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Trade Name: Erbitux
Product Name: Cetuximab
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: CETUXIMAB
CAS Number: 205923-56-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Product Name: Palbociclib
Product Code: PD-0332991
Pharmaceutical Form: Capsule
INN or Proposed INN: Palbociclib
CAS Number: 571190-30-2
Current Sponsor code: PD-0332991
Other descriptive name: PD-332,991
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: Palbociclib
Product Code: PD-0332991
Pharmaceutical Form: Capsule
INN or Proposed INN: Palbociclib
CAS Number: 571190-30-2
Current Sponsor code: PD-0332991
Other descriptive name: PD-332,991
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Trade Name: Erbitux
Product Name: Cetuximab
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: CETUXIMAB
CAS Number: 205923-56-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Please see the protocol for the timepoints.

Primary end point(s): Overall Survival.

Secondary Objective: -To compare secondary measure of efficacy between the treatment arms;
-To compare safety and tolerability between the treatment arms;
-To compare Patient-Reported Outcome (PRO) measures between the treatment arms;
-To characterize the correlations between baseline biomarker (eg, p16, Rb) expression in tumor tissue and clinical efficacy in both treatment arms;
-To characterize steady state trough concentrations for palbociclib, and trough and maximum concentrations for cetuximib in patients with Recurrent/Metastatic Squamous Cell Carcinoma Of The Head and Neck.

Main Objective: To demonstrate that the combination of palbociclib with cetuximab is superior to cetuximab in prolonging Overall Survival in HPV-negative, cetuximab-naïve patients with Recurrent/Metastatic Squamous Cell Carcinoma Of The Head and Neck in whom one prior platinum-containing chemotherapy has failed.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Please see the protocol for the timepoints.

Secondary end point(s): - Progression-free Survival (PFS), Objective Response (OR), and Duration of Response (DR), according to Response Evaluation Criteria in Solid Tumours (RECIST verson [v.] 1.1), as assessed by investigator; - Type, incidence, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v.4.03), seriousness and relationship to study medications of AEs and any laboratory abnormalities;
-Patient Reported Outcome (PRO) endpoints: European Organisation for Research and Treatment of Cancer Quality of Life Instrument (EORTC-QLQ-C30); European Organisation for Research and Treatment of Cancer Head and Neck Module 35 (EORTC-QLQ-H&N35);
-Tumor tissue biomarkers by IHC(p16 and Rb);
-Trough concentrations at steady state for palbociclib; trough and maximum concentrations for cetuximib.

Secondary ID(s)

2015-000515-41-CZ

A5481044

122168

Source(s) of Monetary Support

Pfizer Inc, 235 East 42nd Street, New York, NY 10017