Clinical trial NCT02269943: Safety and Efficacy of CC-486 in Previously Treated Patients With Locally Advanced or Metastatic Nasopharyngeal Carcinoma
Official title: A Phase 2, Multicenter, International, Single Arm Study To Assess The Safety And Efficacy Of Single Agent Cc-486 (Oral Azacitidine) In Previously Treated Subjects With Locally Advanced Or Metastatic Nasopharyngeal Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nasopharyngeal Neoplasms
Keywords: Metastatic nasopharyngeal carcinoma
oral azacitidine
oral AZA
CC-486
metastatic
recurrent
nasopharyngeal carcinoma
nasal
solid tumors
locally advanced
rare head and neck cancer
nasopharynx
single chemotherapy agent
Epstein-Barr Virus (EBV) + nasopharyngeal carcinoma
EBV-DN
Celgene
Sponsor-study
oral chemotherapy
phase 2
oral Vidaza
EBV promoter methylation
hypomethylation
tumor infiltrating lymphocytes (TILs)
EBV gene expression
neoplasms
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2014-10-21
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and efficacy of CC-486 in previously treated patients with locally advanced or metastatic nasopharyngeal carcinoma having failed one to two previous regimens, including platinum-based chemotherapy. Participants will be enrolled according to a Simon two-stage design; if the predefined activity is met (\>4 responses \[complete response; partial response {CR/PR}\] out of the first 17 evaluable participants based on independent radiological assessment), then the study will continue to enroll an additional 34 participants. If 4 or less responses out of 17 are observed, then the study enrollment will be stopped.


Eligibility criteria: Inclusion Criteria:

* Age = or \> 18 years Histological or cytological diagnosis of undifferentiated or poorly differentiated nasopharyngeal carcinoma that is locally advanced or metastatic.
* Disease progression either clinically or radiographically after 1-2 previous regimens.
* Patient has received a platinum containing regimen. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Radiographically-documented measureable disease.
* Adequate organ and bone marrow functions.
* Willingness to follow pregnancy precautions.

Exclusion Criteria:

* History of, or current brain metastasis. Any other malignancy within 5 years prior to randomization with the exception of adequately treated in situ carcinoma of the cervix, uteri, or non-melanomatous skin cancer (all treatment of which should have been completed 6 months prior to enrollment), in situ squamous cell carcinoma of the breast, or incidental prostate cancer.
* Previous treatment with azacitidine (any formulation), decitabine, any other hypomethylating agent.
* History of gastrointestinal disorder or defect. Impaired ability to swallow oral medication. Persistent diarrhea or malabsorption.
* Active cardiac disease and human immunodeficiency virus (HIV) infection
* Active bleeding; pathological condition that carries a high risk of bleeding; risk of pseudoaneurysm of the internal carotid artery and carotid blowout syndrome.
* Major surgery within 14 days prior to starting Investigational Product or has not recovered from major side effects.
* Another investigational therapy within 28 days or 5 half lives of randomization/enrollment, whichever is shorter.
* Patient has not recovered from the acute toxic effects of prior anticancer therapy, radiation, or major surgery/significant trauma.
* Radiotherapy \< or = 4 weeks or limited field radiation for palliation \< or = 2 weeks prior to starting with the investigational product.
* Pregnancy/Breast feeding
* Any condition that places the patient at unacceptable risk if he/she were to participate in the study or that confounds the ability to interpret data from the study.

Primary outcomes:
measure: Percentage of Participants Who Achieved a Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) Based on an Independent Radiology Assessment (IRA)
timeFrame: Tumor response was assessed every (Q) 6 weeks for the first 3 evaluations then Q 9 weeks until disease progression as of the cut-off date of 08 August 2017; the median duration of treatment was 257 days for the 200 mg dose and 114.5 days for 300 mg dose
measure: Kaplan Meier Estimate of Progression-Free Survival (PFS) Based on an Independent Radiology Assessment According to RECIST 1.1 Criteria
timeFrame: From Day 1 of documented disease progression; up to data cut off date of 08 August 2017; median follow-up time for censored participants was 12.3 months
Secondary outcomes:
measure: Kaplan Meier Estimate of Overall Survival
timeFrame: From Day 1 of study treatment to the first date of progressive disease or death; up to data cut-off date of 08 August 2017; overall median follow-up time for censored participants was 20.4 months
measure: Percentage of Participants With Stable Disease for ≥ 16 Weeks From the Date of the First Treatment, or CR or PR According to RECIST 1.1 Criteria and Based on an Independent Radiology Assessment
timeFrame: Tumor response was assessed every 6 weeks for the first 3 evaluations then every 9 weeks until disease progression. As of the cut-off date of 08 August 2017 the median duration of treatment was 257 days for the 200 mg dose and 114.5 days for 300 mg dose
measure: Number of Participants With Treatment Emergent Adverse Events
timeFrame: From date of first dose of study treatment to 28 days after last dose of study treatment; up to final data cut-off date of 08 August 2017; median treatment duration was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg
measure: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration Of CC-486 (AUC-t)
timeFrame: Blood samples for oral azacitidine PK assessment were collected prior to each dose (pre-dose) and over the 8-hour period following each dose (0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose or similar schedule).
measure: Area Under the Plasma Concentration -Time Curve From 0 Extrapolated to Infinity (AUC-inf, AUC0-∞) Of CC-486
timeFrame: Blood samples for oral azacitidine PK assessment were collected prior to each dose (pre-dose) and over the 8-hour period following each dose (0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose or similar schedule).
measure: Maximum Observed Concentration (Cmax) Of CC-486
timeFrame: Blood samples for oral azacitidine PK assessment were collected prior to each dose (pre-dose) and over the 8-hour period following each dose (0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose or similar schedule).
measure: Time to Reach Maximum Concentration (Tmax) Of CC-486
timeFrame: Blood samples for oral azacitidine PK assessment were collected prior to each dose (pre-dose) and over the 8-hour period following each dose (0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose or similar schedule).
measure: Terminal Half-Life (t1/2) of CC-486
timeFrame: Blood samples for oral azacitidine PK assessment were collected prior to each dose (pre-dose) and over the 8-hour period following each dose (0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose or similar schedule).
measure: Apparent Total Clearance (CL/F) Of CC-486
timeFrame: Blood samples for oral azacitidine PK assessment were collected prior to each dose (pre-dose) and over the 8-hour period following each dose (0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose or similar schedule).
measure: Apparent Volume of Distribution (Vz/F) Of CC-486
timeFrame: Blood samples for oral azacitidine PK assessment were collected prior to each dose (pre-dose) and over the 8-hour period following each dose (0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose or similar schedule).
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Jefferson City
country: United States
facility: Columbia Comprehensive Cancer Care Clinic
state: Missouri
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: McGill University
state: Quebec
city: Levallois-Perret
country: France
facility: Institut Hospitalier Franco-Britannique
city: Paris
country: France
facility: Institut Curie
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
city: Heraklion
country: Greece
facility: University General Hospital of Heraklion
city: Thessaloniki
country: Greece
facility: Thermi Clinic
city: Milano
country: Italy
facility: Istituto Nazionale Dei Tumori
city: Singapore
country: Singapore
facility: National Cancer Center
city: Singapore
country: Singapore
facility: Singapore Oncology Consultants
city: Singapore
country: Singapore
facility: Johns Hopkins Singapore International Medical Centre
city: Barcelona
country: Spain
facility: Instituto Catalan de Oncologia-Hospital Duran
city: Madrid
country: Spain
facility: Hospital Universitario Madrid Sanchinarro
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Niao-Sung Hsiang Kaohsiung County
country: Taiwan
facility: Chang Gung Medical Foundation, Kaohsiung Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Ariana
country: Tunisia
facility: Hopital Abderrahman Mami de Pneumo-Phtisiologie de l'Ariana
city: Bab Saadoun
country: Tunisia
facility: Institut Salah Azaiez
city: Sfax
country: Tunisia
facility: Hospital Habib Bourguiba
Study officials:
affiliation: Celgene
name: Abderahim (Rahim) Fandi, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Von Hoff DD, Rasco DW, Heath EI, Munster PN, Schellens JHM, Isambert N, Le Tourneau C, O'Neil B, Mathijssen RHJ, Lopez-Martin JA, Edenfield WJ, Martin M, LoRusso PM, Bray GL, DiMartino J, Nguyen A, Liu K, Laille E, Bendell JC. Phase I Study of CC-486 Alone and in Combination with Carboplatin or nab-Paclitaxel in Patients with Relapsed or Refractory Solid Tumors. Clin Cancer Res. 2018 Sep 1;24(17):4072-4080. doi: 10.1158/1078-0432.CCR-17-3716. Epub 2018 May 15.