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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02269943
• Date of registration: 17/10/2014
• Prospective Registration: Yes
• Primary sponsor: Celgene
• Public title: Safety and Efficacy of CC-486 in Previously Treated Patients With Locally Advanced or Metastatic Nasopharyngeal Carcinoma
• Scientific 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
• Date of first enrolment: February 13, 2015
• Target sample size: 36
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02269943
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Canada, France, Greece, Hong Kong, Italy, Romania, Singapore, Spain, Taiwan, Tunisia, United States

Contacts

• Name: Abderahim (Rahim) Fandi, MD, PhD
• Affiliation: Celgene

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Nasopharyngeal Neoplasms

Intervention(s)

Drug: CC-486

Primary Outcome(s)

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) [Time Frame: 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]

Kaplan Meier Estimate of Progression-Free Survival (PFS) Based on an Independent Radiology Assessment According to RECIST 1.1 Criteria [Time Frame: 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 Outcome(s)

Area Under the Plasma Concentration -Time Curve From 0 Extrapolated to Infinity (AUC-inf, AUC0-8) Of CC-486 [Time Frame: 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).]

Kaplan Meier Estimate of Overall Survival [Time Frame: 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]

Apparent Total Clearance (CL/F) Of CC-486 [Time Frame: 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).]

Terminal Half-Life (t1/2) of CC-486 [Time Frame: 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).]

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

Maximum Observed Concentration (Cmax) Of CC-486 [Time Frame: 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).]

Number of Participants With Treatment Emergent Adverse Events [Time Frame: 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]

Apparent Volume of Distribution (Vz/F) Of CC-486 [Time Frame: 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).]

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 [Time Frame: 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]

Time to Reach Maximum Concentration (Tmax) Of CC-486 [Time Frame: 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).]

Secondary ID(s)

2014-001745-25

CC-486-NPC-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 01/06/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02269943