Urinary Bladder NeoplasmsPhase 1NCT01478685
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 testing CC-486, Carboplatin and ABI-007 in people with Urinary Bladder Neoplasms and Carcinoma, Transitional Cell, run by Celgene at 13 sites in 4 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urinary Bladder Neoplasms, Carcinoma, Transitional Cell, Ovarian Neoplasms
- What is being tested?
- CC-486, Carboplatin and ABI-007
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 169 participants
- Where
- 13 sitesin 4 countries
- Study dates
- 29 Nov 2011to 17 Nov 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women, 18 years or older at the time of signing the Informed Consent Document (ICD).
- Understand and voluntarily sign an ICD prior to any study-related assessments or procedures are conducted.
- Able to adhere to the study visit schedule and other protocol requirements.
- 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.
- Consent to screening tumor biopsy (for accessible tumors when appropriate [optional in Part 1, mandatory in Part 2]).
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
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- 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)
- 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
- 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:
- 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
- Subjects with documented liver metastases must have serum albumin ≥ 3 g/dL;
- Sites of disease (primary or metastatic) that are, in the opinion of the investigator, accessible for biopsy without undue risk to the subject
- Consent to tumor biopsy at screening (prior to the first dose of CC-486) and at Cycle 1 Day 15.
- Measurable disease according to RECIST v1.1.
Who cannot join
- Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
- Any condition that confounds the ability to interpret data from the study.
- Symptomatic central nervous system metastases. Subjects with brain metastases that have been previously treated and are stable for 6 weeks are allowed.
- Known acute or chronic pancreatitis.
- Any peripheral neuropathy ≥ NCI CTCAE grade 2.
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- Persistent diarrhea or malabsorption ≥ NCI CTCAE grade 2, despite medical management.
- Impaired ability to swallow oral medication.
- Unstable angina, significant cardiac arrythmia, or New York Heart Association (NYHA) class 3 or 4 congestive heart failure.
- 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).
- Major surgery ≤ 2 weeks prior to starting a study drug or who have not recovered from side effects of such therapy.
- Pregnant or breast feeding.
- Known Human Immunodeficiency Virus (HIV) infection.
- Known chronic hepatitis B or C virus (HBV/HCV) infection, unless this is a comorbidity in subjects with HCV.
- Liver metastases with serum albumin < 3 g/dL.
- Other prior cancers within previous 5 years except adequately treated in situ carcinoma cervix, or basal, or squamous carcinoma of the skin.
- 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.
Trial locations and contacts
13 sites in 4 countries.
13 sites in 4 countries
United States7 sites
Karmanos Cancer Institute
Detroit, Michigan, 48201-2014
Greenville Hospital
Greenville, South Carolina, 29605
Indiana University Cancer Center
Indianapolis, Indiana, 46202
Sarah Cannon Research Institute
Nashville, Tennessee, 37205
South Texas Accelerated Research Therapeutics
San Antonio, Texas, 78229
University of California, San Francisco
San Francisco, California, 94115
Scottsdale Healthcare Research Institute
Scottsdale, Arizona, 85258
France2 sites
Centre Georges Francois Leclerc
Dijon, 21079
Institut Curie
Paris, 75005
Netherlands2 sites
The Netherlands Cancer Instiute Antoni Van Leeuwenhoekziekenhuis
Amsterdam, 1066 CX
Erasmus Medical Center
Rotterdam, 3015 CN
Spain2 sites
Hospital General Universitario Gregorio Maranon
Madrid, 28007
Hospital Universitario 12 de Octubre
Madrid, 28041
About this study
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.
- Conditions
- Urinary Bladder Neoplasms, Carcinoma, Transitional Cell, Ovarian Neoplasms, Fallopian Tube Neoplasms, Peritoneal Neoplasms, Carcinoma, Non-Small-Cell Lung
- Being tested
- CC-486, Carboplatin, ABI-007
- Keywords
- Relapsed or Refractory Solid Tumors
- Medical subject headings
- Urinary Bladder Neoplasms, Carcinoma, Transitional Cell, Ovarian Neoplasms, Fallopian Tube Neoplasms, Peritoneal Neoplasms, Carcinoma, Non-Small-Cell Lung, Carcinoma, Pancreatic Ductal, Tumor Virus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CC-486Drug
Also called Oral Azacitidine
CC-486 will be administered orally at doses between 100-300 mg daily for either 14 or 21 days depending on tolerability
CarboplatinDrug
Also called Paraplatin
Carboplatin will be given by intravenous (IV) infusion once every 21 Days at a dosage of AUC x 4.
ABI-007Drug
Also called nab-paclitaxel, Abraxane
ABI-007 will be administered by intravenous (IV) infusion on two of every three weeks at a dosage of 100 mg/m^2
| Study group | Role | What they receive |
|---|---|---|
| Arm A: CC-486 plus Carboplatin | Experimental | CC-486 will be administered orally at doses between 100-300 mg daily for either 14 or 21 days depending on tolerability. Carboplatin will be given by intravenous (IV) infusion once every 21 Days at a dosage of AUC x 4. Receives: Drug: CC-486; Drug: Carboplatin |
| Arm B: CC-486 plus ABI-007 | Experimental | CC-486 will be administered orally at doses between 100-300 mg daily for either 14 or 21 days depending on tolerability
ABI-007 will be administered by intravenous (IV) infusion on two of every three weeks at a dosage of 100 mg/m^2 Receives: Drug: CC-486; Drug: ABI-007 |
| Arm C: CC-486 | Experimental | CC-486 will be administered orally at doses between 100-300 mg daily for either 14 or 21 days depending on tolerability Receives: Drug: CC-486 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events
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.
Measured: Up to 3 years
Secondary outcomes (11)
Cmax
Maximum observed concentration in plasma (Cmax)
Measured: Up to 30 days
AUC
Area under the concentration-time curve (AUC)
Measured: Up to 30 days
Tmax
Time to maximum concentration (tmax);
Measured: Up to 30 days
T1/2
Terminal half-life (t1/2)
Measured: Up to 30 days
CL/F
Apparent total body clearance (CL/F)
Measured: Up to 30 days
Vz/F
Apparent volume of distribution (Vz/F).
Measured: Up to 30 days
DNA Methylation
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)
Measured: Up to 30 days
DNMT1 protein levels
Reduction from baseline (Cycle 1 Day 1 predose) in DNMT1 protein levels in tumor tissue (as available in Part 1)
Measured: Up to 30 days
Tumor Response Rate
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
Measured: Up to 3 years
Progression Free Survival
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.
Measured: Up to 3 years
Duration of Response
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
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2011 (estimated)
- Study start29 Nov 2011
- Primary completion17 Nov 2015
- Study completion17 Nov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Urinary Bladder NeoplasmsStudies of the same condition, open and under way.
- More trials run by CelgeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 169 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gordan Bray, M.D., Ph.D, Study director, Celgene
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01478685
- Sponsor's protocol ID
- AZA-ST-001
- Status last verified
- Nov 2019
- First submitted
- 21 Nov 2011
- Last updated
- 12 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
LoRusso P, et al. A Phase Ib study of CC-486 (Oral Azacitidine) as a priming agent for carboplatin or NAB-paclitaxel in subjects with relapsed and refractory solid tumors . Presented at 25th AACR-NCI-EORTC Symposium on Molecular Targets and Cancer Therapeutics, October 19-23, 2013, Boston, MA. Abstract No. A120.
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01478685
- Acronym / sponsor ID
- AZA-ST-001
- Conditions
- Urinary Bladder Neoplasms, Carcinoma, Transitional Cell, Ovarian Neoplasms, Fallopian Tube Neoplasms, Peritoneal Neoplasms, Carcinoma, Non-Small-Cell Lung
- Keywords
- Relapsed or Refractory Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 169 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Study start
- 29 Nov 2011 (actual)
- Primary completion
- 17 Nov 2015 (actual)
- Study completion
- 17 Nov 2015 (actual)
- First posted
- 23 Nov 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A: CC-486 plus Carboplatin | Experimental | Drug: CC-486, Drug: CarboplatinCC-486 will be administered orally at doses between 100-300 mg daily for either 14 or 21 days depending on tolerability. Carboplatin will be given by intravenous (IV) infusion once every 21 Days at a dosage of AUC x 4. |
| Arm B: CC-486 plus ABI-007 | Experimental | Drug: CC-486, Drug: ABI-007CC-486 will be administered orally at doses between 100-300 mg daily for either 14 or 21 days depending on tolerability ABI-007 will be administered by intravenous (IV) infusion on two of every three weeks at a dosage of 100 mg/m^2 |
| Arm C: CC-486 | Experimental | Drug: CC-486CC-486 will be administered orally at doses between 100-300 mg daily for either 14 or 21 days depending on tolerability |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (41 listed)
- Men and women, 18 years or older at the time of signing the Informed Consent Document (ICD).
- Understand and voluntarily sign an ICD prior to any study-related assessments or procedures are conducted.
- Able to adhere to the study visit schedule and other protocol requirements.
- 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.
- Consent to screening tumor biopsy (for accessible tumors when appropriate [optional in Part 1, mandatory in Part 2]).
Key exclusion criteria (17 listed)
- Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
- Any condition that confounds the ability to interpret data from the study.
- Symptomatic central nervous system metastases. Subjects with brain metastases that have been previously treated and are stable for 6 weeks are allowed.
- Known acute or chronic pancreatitis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CC-486Also: Oral AzacitidineCC-486 will be administered orally at doses between 100-300 mg daily for either 14 or 21 days depending on tolerability | Drug | Arm A: CC-486 plus Carboplatin, Arm B: CC-486 plus ABI-007, Arm C: CC-486 |
| CarboplatinAlso: ParaplatinCarboplatin will be given by intravenous (IV) infusion once every 21 Days at a dosage of AUC x 4. | Drug | Arm A: CC-486 plus Carboplatin |
| ABI-007Also: nab-paclitaxel, AbraxaneABI-007 will be administered by intravenous (IV) infusion on two of every three weeks at a dosage of 100 mg/m^2 | Drug | Arm B: CC-486 plus ABI-007 |
Primary outcome
Number of participants with adverse events
Time frame: Up to 3 years
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.
11 secondary outcomes
Cmax
Time frame: Up to 30 days
AUC
Time frame: Up to 30 days
Tmax
Time frame: Up to 30 days
T1/2
Time frame: Up to 30 days
CL/F
Time frame: Up to 30 days
Vz/F
Time frame: Up to 30 days
DNA Methylation
Time frame: Up to 30 days
DNMT1 protein levels
Time frame: Up to 30 days
Tumor Response Rate
Time frame: Up to 3 years
Progression Free Survival
Time frame: Up to 3 years
Duration of Response
Time frame: Up to 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2019.
- BackgroundLoRusso P, et al. A Phase Ib study of CC-486 (Oral Azacitidine) as a priming agent for carboplatin or NAB-paclitaxel in subjects with relapsed and refractory solid tumors . Presented at 25th AACR-NCI-EORTC Symposium on Molecular Targets and Cancer Therapeutics, October 19-23, 2013, Boston, MA. Abstract No. A120.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gordan Bray, M.D., Ph.D study director
Celgene
13 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CC-486, Carboplatin and ABI-007 in people with Urinary Bladder Neoplasms and Carcinoma, Transitional Cell, run by Celgene at 13 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 41 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, France, Netherlands, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with adverse events (time frame: Up to 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01478685, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Nov 2019.