A Phase 1 Study of CC-486 as a Single Agent and in Combination With Carboplatin or ABI-007 in Subjects With Relapsed or Refractory Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Celgene Corporation
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01478685
First received: November 21, 2011
Last updated: July 3, 2014
Last verified: July 2014

November 21, 2011
July 3, 2014
November 2011
November 2014   (final data collection date for primary outcome measure)
Number of participants with adverse events [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity.
Adverse Events [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
Number of participants with adverse events using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, Version 4.0.
Complete list of historical versions of study NCT01478685 on ClinicalTrials.gov Archive Site
  • Cmax [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
    Maximum observed concentration in plasma (Cmax)
  • AUC [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
    Area under the concentration-time curve (AUC)
  • Tmax [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
    Time to maximum concentration (tmax);
  • T1/2 [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
    Terminal half-life (t1/2)
  • CL/F [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
    Apparent total body clearance (CL/F)
  • Vz/F [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
    Apparent volume of distribution (Vz/F).
  • DNA Methylation [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
    Change from baseline (Cycle 1 Day 1 pre-dose) in DNA methylation (global and gene-specific assays) in whole blood and tumor tissue (as available in Part 1)
  • DNMT1 protein levels [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
    Reduction from baseline (Cycle 1 Day 1 predose) in DNMT1 protein levels in tumor tissue (as available in Part 1)
  • Tumor Response Rate [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

    Response and progression were evaluated using the RECIST 1.1 criteria. Treatment response includes both complete response and partial response.

    • Complete response-disappearance of all lesions
    • Partial response-30% decrease in the sum of diameters of target lesions from baseline
  • Progression Free Survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Progression-free survival is defined as the time from first dose of study drug to the start of disease progression or patient death, whichever occurs first.
  • Duration of Response [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Duration of response is defined as progression-free survival in responders, i.e. as the time between the start of a complete response (CR) or partial response (PR) and the start of progressive disease (PD) or patient death from any cause, whichever occurred first
  • Cmax [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
    maximum observed concentration in plasma (Cmax)
  • AUC [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
    area under the concentration-time curve (AUC)
  • tmax [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
    time to maximum concentration (tmax);
  • (t1/2) [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
    terminal half-life (t1/2)
  • (CL/F) [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
    apparent total body clearance (CL/F)
  • (Vz/F) [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
    apparent volume of distribution (Vz/F).
  • DNA Methylation [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
    Change from baseline (Cycle 1 Day 1 pre-dose) in DNA methylation (global and gene-specific assays) in whole blood and tumor tissue (as available in Part 1)
  • DNMT1 protein levels [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
    Reduction from baseline (Cycle 1 Day 1 predose) in DNMT1 protein levels in tumor tissue (as available in Part 1)
  • Tumor response rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Tumor response rate
  • Number of participants who survive without disease progression [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Number of participants who survive without disease progression
Not Provided
Not Provided
 
A Phase 1 Study of CC-486 as a Single Agent and in Combination With Carboplatin or ABI-007 in Subjects With Relapsed or Refractory Solid Tumors
A Phase 1 Study of CC-486 as a Single Agent and in Combination With Carboplatin or ABI-007 in Subjects With Relapsed or Refractory Solid Tumors

The purpose of the study is to evaluate the safety and to define the Maximal Tolerated Dose (MTD) or the Maximal Administered Dose (MAD) of oral azacitidine as a single agent and in combination with carboplatin (CBDCA) or paclitaxel protein bound particles (ABI-007,ABX) in subjects with relapsed or refractory solid tumors.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Urinary Bladder Neoplasms
  • Carcinoma, Transitional Cell
  • Ovarian Neoplasms
  • Fallopian Tube Neoplasms
  • Peritoneal Neoplasms
  • Carcinoma, Non-Small-Cell Lung
  • Carcinoma, Pancreatic Ductal
  • Tumor Virus Infections
  • Drug: CC-486 plus Carboplatin
    CC-486 will be administered at doses between 100-300 mg daily for either 14 or 21 days depending on tolerability. Carboplatin will be given once every 21 Days at a dosage of AUC x4.
  • Drug: CC-486 plus ABI-007

    CC-486 will be administered at doses between 100-300 mg daily for either 14 or 21 days depending on tolerability

    ABI-007 will be administered on two of every three weeks at a dosage of 100 mg/m2

  • Drug: CC-486
    CC-486 will be administered at doses between 100-300 mg daily for either 14 or 21 days depending on tolerability
  • Experimental: Arm A: CC-486 plus Carboplatin
    Intervention: Drug: CC-486 plus Carboplatin
  • Experimental: Arm B: CC-486 plus ABI-007
    Intervention: Drug: CC-486 plus ABI-007
  • Experimental: Arm C: CC-486
    Intervention: Drug: CC-486
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
180
January 2015
November 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Men and women, 18 years or older at the time of signing the Informed Consent Document (ICD).
  2. Understand and voluntarily sign an ICD prior to any study-related assessments or procedures are conducted.
  3. Able to adhere to the study visit schedule and other protocol requirements.
  4. With histological or cytological confirmation of advanced unresectable solid tumors, including those who have progressed on (or not been able to tolerate) standard anticancer therapy, or for whom no other effective therapy exists, or for who declines standard therapy.
  5. Consent to screening tumor biopsy (for accessible tumors when appropriate [optional in Part 1, mandatory in Part 2]).
  6. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
  7. The following laboratory values:

    • Absolute neutrophil count (ANC) ≥ 1.5 X 10^9/L
    • Hemoglobin (Hgb) ≥90 g/L
    • Platelets (plt) ≥ 100 x 10^9/L
    • Potassium within normal range, or correctable with supplements;
    • AST and ALT ≤2.5 x Upper Limit Normal (ULN) or ≤5.0 x ULN if liver tumor is present;
    • Serum total bilirubin ≤ 1.5 x ULN
    • Serum creatinine ≤ 1.5 x ULN, or 24-hr clearance ≥ 60ml/min; and
    • Negative serum pregnancy test within 7 days before starting study treatment in females of childbearing potential (FCBP)
  8. Females of child-bearing potential {defined as a sexually mature women who

    • has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or,
    • has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time during the preceding 24 consecutive months} must

      • agree to the use of a physician- approved contraceptive method (oral, injectable, or implantable hormonal contraceptive ; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on oral azacitidine and for 3 months following the last dose of study medication; and
      • have a negative serum pregnancy test during screening
  9. Male subjects with female partner of childbearing potential must agree to the use of a physician-approved contraceptive method throughout the course of the study to avoid fathering a child during the course of the study and for 6 months following the last dose of oral azacitidine.

The criteria below are in addition to or supersede the Part 1 inclusion criteria above:

  1. With histological or cytological confirmation of relapsed or refractory advanced unresectable solid tumors as listed below for each Arm, including those who have progressed on or were unable to tolerate standard anti-cancer therapy.

    • Arm A: CC-486 plus CBDCA:
    • Relapsed or refractory urothelial carcinoma of the bladder, renal pelvis, ureter, or urethra (mixed histologies are permitted provided a component of urothelial carcinoma is present)
    • Epithelial ovarian, fallopian tube, or primary peritoneal carcinoma
    • Arm B: CC-486 plus ABI-007:
    • NSCLC
    • Pancreatic carcinoma
    • Arm C: CC-486 single agent:
    • Virally-associated tumors - tumor types known to be driven by Epstein-Barr Virus (EBV), Human Papilloma Virus (HPV), and Merkel cell carcinoma of the skin (MC Polomavirus)
    • Nasopharyngeal carcinoma (a minimum of 5 subjects)
    • Cervical carcinoma
    • Anal carcinoma
    • Merkel cell carcinoma (MCC)
    • Note: Hepatitis B virus (HBV) and Hepatitis C virus (HCV)-associated tumors (hepatocellular cancers) are not eligible.
    • Note: Head and neck squamous cell cancers (HNSCC) must have HPV-positive status documented to be eligible
  2. Subjects with documented liver metastases must have serum albumin ≥ 3 g/dL;
  3. Sites of disease (primary or metastatic) that are, in the opinion of the investigator, accessible for biopsy without undue risk to the subject
  4. Consent to tumor biopsy at screening (prior to the first dose of CC-486) and at Cycle 1 Day 15.
  5. Measurable disease according to RECIST v1.1.

Exclusion Criteria:

  1. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
  2. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
  3. Any condition that confounds the ability to interpret data from the study.
  4. Symptomatic central nervous system metastases. Subjects with brain metastases that have been previously treated and are stable for 6 weeks are allowed.
  5. Known acute or chronic pancreatitis.
  6. Any peripheral neuropathy ≥ NCI CTCAE grade 2.
  7. Persistent diarrhea or malabsorption ≥ NCI CTCAE grade 2, despite medical management.
  8. Impaired ability to swallow oral medication.
  9. Unstable angina, significant cardiac arrythmia, or New York Heart Association (NYHA) class 3 or 4 congestive heart failure.
  10. Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives or 4 weeks, whichever is shorter, prior to starting study drug or who have not recovered from side effects of such therapy. (except alopecia).
  11. Major surgery ≤ 2 weeks prior to starting a study drug or who have not recovered from side effects of such therapy.
  12. Pregnant or breast feeding.
  13. Known Human Immunodeficiency Virus (HIV) infection.
  14. Known chronic hepatitis B or C virus (HBV/HCV) infection, unless this is a comorbidity in subjects with HCV.
  15. Liver metastases with serum albumin < 3 g/dL.
  16. Other prior cancers within previous 5 years except adequately treated in situ carcinoma cervix, or basal, or squamous carcinoma of the skin.
  17. Subjects with > 4 prior systemic chemotherapy regimens will require approval by the Celgene Medical Monitor prior to enrollment. A regimen is defined as >/= 2 cycles of systemic anti-cancer therapy containing 1 or more agents in the following classes: topoisomerase 1 or 2 inhibitors, platinum salts, alkylating agents, tubulin inhibitors, anti-metabolites or vinca alkaloids.
Both
18 Years and older
No
Contact: Associate Director, Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com
United States,   France,   Netherlands,   Spain
 
NCT01478685
AZA-ST-001
No
Celgene Corporation
Celgene Corporation
Not Provided
Study Director: Gordan Bray, M.D., Ph.D Celgene Corporation
Celgene Corporation
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP