relapsed or refractory solid tumors. Tumors that did not respond to treatment or have returned after treatment
Conditions
Interventions
Subjects enrolled in the study will be assigned treatment as outlined by the
following relapsed or refractory tumor types:
* CC-486 plus carboplatin (CBDCA) (Arm A):
* Urothelial carcinoma of the bla
Sponsors
Celgene Corporation
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1.Men and women, 18 years or older 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. 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 not been able to tolerate) standard anti-cancer therapy * Arm A: CC-486 plus CBDCA: - 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 as a single agent: - Virally associated tumors (tumor types known to be driven by Epstein-Barr virus, 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 carcinioma (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. 5. Consent to screening tumor biopsy (prior to the first dose of CC-486) and at cycle 1 day 15 6. Eastern Cooperative Oncology Group (ECOG) Performance Status of * 2. 7. Absolute neutrophil count (ANC) * 1.5 x 109/L; Hemoglobin (Hgb) * 90 g/L; Platelets (plt) * 100 x 109/L; Potassium within normal range, or correctable with supplements; AST and ALT * 2.5 x Upper Limit of 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 * 60 mL/min; and, Negative serum pregnancy test within 72 hours before starting study treatment in females of childbearing potential (FCBP). 8. Females of child-bearing potential (defined as a sexually mature woman who 1) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or, 2) has not been naturally postmenopausal for at least 24 consecutive months (ie, 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 CC-486; and for 3 months following the last dose of study medication; and * Have a medically supervised serum pregnancy test with sensitivity of at least 25mIU/mL is to be obtained in FCBP at Screening. A serum pregnancy test should be done within 72 hours prior to Day 1 of starting study therapy (note that the screening serum pregnancy test can be used as the test prior to Day 1 study therapy if it is performed within the 72-hour timeframe). A serum pregnancy test should be done within 72 hours prior to Day 1 of every cycle, and at the Treatment Discontinuation visit. The subject may not receive investigational product until the investigator has verified that the result of the pregnancy test is negative. 9. Male subjects with a fe
Exclusion criteria
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 arrhythmia, 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 study drug or who have not recovered from side effects of such therapy. 12. Pregnant or breast feeding. 13. Known HIV infection. 14. Known chronic hepatitis B or C virus (HBV/HCV) infection, unless this is a comorbidity in subjects with HCC. 15. Liver metastases with serum albumin lower or equal to 3 g/dL. 16. Other prior cancers within previous 5 years except adequately treated in situ carcinoma cervix, 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The nature, incidence and severity of AEs will be evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria, Version 4.0. | — |
Secondary
| Measure | Time frame |
|---|---|
| For CC-486 (administered alone and in combination), CBDCA, ABI-007 , the following plasma PK parameters will be assessed: * maximum observed concentration in plasma (Cmax); * area under the concentration-time curve (AUC); * time to maximum concentration (tmax); * terminal half-life (t1/2); * apparent total body clearance (CL/F); and, * apparent volume of distribution (Vz/F). To evaluate the PD effects of CC-486 in blood, plasma, and tumor tissue, the following molecular characterizations will be performed; * 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); and, * Reduction from baseline (Cycle 1 Day 1 predose) in DNMT1 protein levels in tumor tissue (as available in Part 1). Anti-tumor activity endpoints using tumor-specific response criteria for each tumor type will include: * Response rate and duration of response; * Progression-free survival (PFS); and, * See definition of response in statistical analysis section. Exploratory Endpoints - CC-486 Response Molecular characteristics of the blood and tumor, potentially including, but not limited to, DNA/RNA methylation, gene sequence and mRNA/miRNA expression may be evaluated at baseline and post-therapy for examination in relation to tumor responses. | — |
Countries
Netherlands
Outcome results
None listed