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

NCT02269943 | Completed Phase 2 Results

• 2 other identifiers: CC-486-NPC-0012014-001745-25
• Study Type: interventional
• Target: 36
• Locations: 9 countries
• Sites: 25

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.

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

Outcome Measures

Primary Outcomes (2)

• 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)

  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.

  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

  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.

  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 (10)

• Kaplan Meier Estimate of Overall Survival

  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

• 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

  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

• Number of Participants With Treatment Emergent Adverse Events

  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

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

  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 0 Extrapolated to Infinity (AUC-inf, AUC0-∞) Of CC-486

  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).

Study Arms (1)

CC-486

EXPERIMENTAL

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.

Drug: CC-486

Interventions

CC-486 DRUG

Also known as: oral azacitidine

CC-486

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Celgene: lead

Study Sites (25)

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Columbia Comprehensive Cancer Care Clinic

Jefferson City, Missouri, 65101, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

McGill University

Montreal, Quebec, H2W 1S6, Canada

Location

Institut Hospitalier Franco-Britannique

Levallois-Perret, 92300, France

Location

Institut Curie

Paris, 75005, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

University General Hospital of Heraklion

Heraklion, 71110, Greece

Location

Thermi Clinic

Thessaloniki, 56429, Greece

Location

Istituto Nazionale Dei Tumori

Milan, 20133, Italy

Location

National Cancer Center

Singapore, 169-610, Singapore

Location

Singapore Oncology Consultants

Singapore, 258500, Singapore

Location

Johns Hopkins Singapore International Medical Centre

Singapore, 308433, Singapore

Location

Instituto Catalan de Oncologia-Hospital Duran

Barcelona, 08907, Spain

Location

Hospital Universitario Madrid Sanchinarro

Madrid, 28050, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Chang Gung Medical Foundation, Kaohsiung Memorial Hospital

Niao-Sung Hsiang Kaohsiung County, 83301, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

Hopital Abderrahman Mami de Pneumo-Phtisiologie de l'Ariana

Aryanah, 2080, Tunisia

Location

Institut Salah Azaiez

Bab Saadoun, 1006, Tunisia

Location

Hospital Habib Bourguiba

Sfax, 3029, Tunisia

Location

Related Publications (1)

• 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.

  PMID: 29764853 DERIVED

MeSH Terms

Conditions

Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Neoplasm Metastasis; Recurrence; Head and Neck Neoplasms; Epstein-Barr Virus Infections; Neoplasms

Interventions

cc-486; Azacitidine

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Limitations and Caveats

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.

Results Point of Contact

• Title: Anne McClain, Senior Manager, Clinical Trial Disclosure
• Organization: Celgene Corporation

ClinicalTrialDisclosure@celgene.com

888-260-1599

Study Officials

• Abderahim (Rahim) Fandi, MD, PhD

  Celgene

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: October 17, 2014
• First Posted: October 21, 2014
• Study Start: February 13, 2015
• Primary Completion: April 20, 2017
• Study Completion: April 20, 2017
• Last Updated: December 12, 2018
• Results First Posted: June 1, 2018

Record last verified: 2018-11

Locations

US (5); IT (1); CA (2); TW (3); TU (3); SG (3); GR (2); FR (3); ES (3)