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Pharyngeal Neoplasms

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Antineoplastic Agents

All Drugs and Chemicals

Azacitidine

Cc-486

Antimetabolites

Enzyme Inhibitors

CC-486 will be administered orally every day on Days 1-14 of a 21 day cycle at a dose of 300 mg. The first 6 participants of Asian-Pacific ethnicity will receive a starting dose of 200 mg. If there are no safety concerns, the 300 mg dose will be administered to all subsequent participants of Asian-Pacific ethnicity.

CC-486

Abderahim (Rahim) Fandi, MD, PhD

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.

Safety and Efficacy of CC-486 in Previously Treated Patients With Locally Advanced or Metastatic Nasopharyngeal Carcinoma

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

Overall response rate was defined as the combined incidence of Complete Response (CR) or Partial Response (PR), confirmed no less than 4 weeks after the criteria for response were first met, based on independent radiology assessment according to RECIST 1.1 criteria.

Complete response was defined as the disappearance of all target lesions and non-target lesions; Partial response is at least a 30% decrease from baseline in the sum of diameters of target lesions with no progression of non-target lesions and no new lesions or disappearance of target lesions with persistence of one or more non-target lesions from baseline.

PFS was defined as the time from the date of start of the study treatment to the date of disease progression or death (any cause) on or prior to the data cut-off date for the statistical analysis, whichever occurred earlier, based on an independent radiology assessment of response using RECIST v1.1 criteria. Progressive disease was defined as at least a 20% increase in the sum of diameters of target or non-target lesions from nadir or appearance of a new lesion.

Overall survival was the time from the first dose of study drug to patient death from any cause. Participants who did not die were censored at the last known time the patient was alive date or the clinical data cutoff date, whichever was earlier.

Disease Control Rate (DCR) was defined as the percentage of participants with a CR, PR, confirmed ≥ 4 weeks after the criteria for response were first met, or stable disease for ≥ 16 weeks from the first treatment, based on independent radiology assessment using RECIST 1.1 criteria. A complete response was defined as the disappearance of all target lesions and non-target lesions; a partial response is at least a 30% decrease from baseline in the sum of diameters of target lesions with no progression of non-target lesions and no new lesions or disappearance of target lesions with persistence of one or more non-target lesions from baseline. Stable disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for progressive disease

Treatment-emergent adverse events (TEAEs) were defined as any adverse event (AE) or serious adverse event (SAE) that occurred or worsened on or after the day of the first dose of the investigational product (IP) through 28 days after the last dose of IP. In addition, any SAE with an onset date more than 28 day after the last dose of IP that was assessed by the investigator as related to IP was considered a TEAE. The severity of AEs was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 and based on the following scale: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death.

Area under the plasma concentration-time curve from Time 0 to the time of the last quantifiable concentration, calculated by linear trapezoidal method when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing.

Area under the plasma concentration-time curve from Time 0 extrapolated to infinity, calculated as \[AUCt + Ct/ λz\]. Ct is the last quantifiable concentration. No AUC extrapolation was performed with unreliable λz. If AUC %Extrap was ≥25%, AUC inf was not reported.

Maximum observed plasma concentration, obtained directly from the observed concentration versus time data.

Time to Cmax, obtained directly from the observed concentration versus time data.

Terminal phase half-life in plasma, calculated as \[(ln 2)/λz\]. t1/2 was only calculated when a reliable estimate for λz could be obtained.

Apparent volume of distribution, calculated as \[(CL/F)/λz\].

Celgene

Asian-Pacific island participants received CC-486 200 mg tablets by mouth (PO) on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event, a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. If well tolerated, and there were no safety concerns, subsequent participants of Asian-Pacific Island ethnicity were administered CC-486 300-mg PO daily for 14 days of a 21-day cycle.

CC-486 200 mg

Participants received CC-486 300 mg tablets by mouth on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event (AE), a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death.

CC-486 300 mg

Total

Age, Continuous

Sex: Female, Male

Asian

White

Race/Ethnicity, Customized

Hispanic

Non-Hispanic or Latino

0 = Fully Active

1 = Restrictive but ambulatory

2 = Ambulatory but unable to work

3 = Limited Self-Care

ECOG performance status is used by doctors and researchers to assess how a subject's disease is progressing, assess how the disease affects the daily living activities of the subject and determine appropriate treatment and prognosis. 0 = Fully Active (Most Favorable Activity); 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, No self-care (Least Favorable Activity)

Eastern Cooperative Oncology Group (ECOG) Performance Status

Time From Initial Diagnosis to First Dose

Undifferentiated Nasopharyngeal Carcinoma

Poorly Differentiated Nasopharyngeal Carcinoma

Other

The 3 types of NPC, based on how the cancer cells look under the microscope include:

1. Undifferentiated Nasopharyngeal Carcinoma
2. Poorly Differentiated Nasopharyngeal Carcinoma
3. Other

Nasopharyngeal Cancer (NPC) Diagnosis Types

The Safety Population included all participants who received at least

1 dose of investigational product (IP)

Participants with Prior Anti-Cancer Therapies

Enrolled Population: The Enrolled Population included all participants who were enrolled to the study.

The review of the efficacy data from the trial participants did not support proceeding to Stage 2 as the protocol-defined criteria of \> 4 responders (a best response of CR or PR) in Stage 1 was not reached and study enrollment was stopped.

Anne McClain, Senior Manager, Clinical Trial Disclosure

The Efficacy Evaluable Population included all enrolled participants who met eligibility criteria and either received 2 cycles of CC-486 at any dose and discontinued treatment for progressive disease or received 4 cycles of CC-486 and had a baseline and at least 2 post-screening tumor assessments.

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)

Kaplan Meier Estimate of Progression-Free Survival (PFS) Based on an Independent Radiology Assessment According to RECIST 1.1 Criteria

Kaplan Meier Estimate of Overall Survival

Efficacy Evaluable Population = enrolled participants who met eligibility criteria and either received 2 cycles of IP at any dose and discontinued treatment for progressive disease or received 4 cycles of IP and had at least 2 post-screening tumor exams.

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

Any TEAE

Any TEAE Related to IP

Any Serious TEAE

Any Serious TEAE Related to IP

Any CTCAE Grade 3 or 4 TEAE

Any CTCAE Grade 3 or 4 TEAE Related to IP

Any TEAE Leading to Death

Any TEAE Leading to Dose Reduction

Any TEAE Leading to Drug Interruption

Any TEAE Leading to IP Discontinuation

The Safety Population included all participants who received at least 1 dose of IP.

Number of Participants With Treatment Emergent Adverse Events

Cycle 1 Day 1

Cycle 1 Day 14

The PK population includes participants with evaluable CC-486 plasma PK profiles.

Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration Of CC-486 (AUC-t)

Area Under the Plasma Concentration -Time Curve From 0 Extrapolated to Infinity (AUC-inf, AUC0-∞) Of CC-486

The PK population includes participants with evaluable CC-486 plasma PK profiles

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Safety and Efficacy of CC-486 in Previously Treated Patients With Locally Advanced or Metastatic Nasopharyngeal Carcinoma	NCT02269943	Nasopharyngeal ...	CC-486	18 Years -	Celgene
Safety and Efficacy of CC-486 in Previously Treated Patients With Locally Advanced or Metastatic Nasopharyngeal Carcinoma	NCT02269943	Nasopharyngeal ...	CC-486	18 Years -	Celgene

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