Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT02334527
Previous Study | Return to List | Next Study

Phase II Trial of Palbociclib in Patients With Metastatic Urothelial Cancer After Failure of First-Line Chemotherapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02334527
Recruitment Status : Terminated (Data from first 12 subjects-primary endpoint not met. Data analysis underway.)
First Posted : January 8, 2015
Results First Posted : April 24, 2018
Last Update Posted : November 16, 2018
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE January 6, 2015
First Posted Date  ICMJE January 8, 2015
Results First Submitted Date  ICMJE February 6, 2018
Results First Posted Date  ICMJE April 24, 2018
Last Update Posted Date November 16, 2018
Actual Study Start Date  ICMJE March 17, 2015
Actual Primary Completion Date December 2, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 23, 2018)
Progression Free Survival [ Time Frame: 4 Months ]
Estimate progression free survival (PFS) at 4 months in patients with metastatic urothelial cancer (UC) who have progressed after first-line chemotherapy. PFS is defined as the percent of patients who are alive and free from progression at 4 months.
Original Primary Outcome Measures  ICMJE
 (submitted: January 6, 2015)
Progression Free Survival [ Time Frame: 4 Months ]
Estimate progression free survival (PFS) at 4 months in patients with metastatic UC who have progressed after first-line chemotherapy
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 26, 2018)
  • Progression Free Survival (PFS) [ Time Frame: 4 Months ]
    PFS is defined as the time from D1 of treatment until progression or death as a result of any cause. Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
  • Overall Survival (OS) [ Time Frame: Patients will be followed for up to 5 years after removal from study therapy or death, whichever occurs first. ]
    Overall survival is defined as the time from day 1 of treatment until death as a result of any cause.
  • Response Rate (RR) - Total Number of Patients With Complete Response (CR) and/or Partial Response (PR) [ Time Frame: 4 Months ]
    Estimate response rate (RR) in patients with metastatic UC who have progressed after first-line chemotherapy. Response rate will be the number of patients with complete response and/or partial response. Response will be based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Radiographic response will be measured by RECIST, Response Evaluation Criteria In Solid Tumors Criteria, indicating if subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
  • Number of Participants With Adverse Events [ Time Frame: 30 Days ]
    Characterize the safety profile of palbociclib in patients with metastatic UC after first-line chemotherapy. The NCI Common Terminology Criteria for Adverse Events is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 6, 2015)
  • Progression Free Survival (PFS) and Overall Survival (OS) [ Time Frame: 4 Months ]
    Estimate median progression free survival (PFS) and overall survival (OS) in patients with metastatic UC who have progressed after first-line chemotherapy
  • Response Rate (RR) [ Time Frame: 4 Months ]
    Estimate response rate (RR) in patients with metastatic UC who have progressed after first-line chemotherapy.
  • Number of participants with adverse events [ Time Frame: 30 Days ]
    Characterize the safety profile of palbociclib in patients with metastatic UC after first-line chemotherapy.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase II Trial of Palbociclib in Patients With Metastatic Urothelial Cancer After Failure of First-Line Chemotherapy
Official Title  ICMJE Phase II Trial of Palbociclib (PD-0332991) in Patients With Metastatic Urothelial Cancer (UC) After Failure of First-Line Chemotherapy
Brief Summary This multicenter phase II trial will evaluate palbociclib (PD-0332991) in patients with metastatic urothelial carcinoma (UC) with cyclin-dependent kinase inhibitor 2A (CDKN2A) (also referred to as p16) loss and positive Retinoblastoma (Rb) expression after failure of first-line chemotherapy.
Detailed Description This multicenter phase II trial will evaluate palbociclib (PD-0332991) in patients with metastatic urothelial carcinoma (UC) with cyclin-dependent kinase inhibitor 2A (CDKN2A) (also referred to as p16) loss and positive Retinoblastoma (Rb) expression after failure of first-line chemotherapy. The study will enroll up to 40 patients to identify 36 evaluable patients, using a Simon's two-stage design, with a primary endpoint of progression free survival (PFS) at 4 months (PFS4). Secondary objectives include estimating median PFS, overall survival (OS), response rate (RR) and exploratory objectives include an evaluation of molecular predictors of response and resistance.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Urothelial Carcinoma (UC)
Intervention  ICMJE Drug: Palbociclib
125 mg capsule will be taken once per day orally and continuously for 3 weeks followed by 1 week off.
Other Name: PD-0332991
Study Arms  ICMJE Palbociclib Single Arm trial
Palbociclib
Intervention: Drug: Palbociclib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 20, 2017)
12
Original Estimated Enrollment  ICMJE
 (submitted: January 6, 2015)
40
Actual Study Completion Date  ICMJE September 28, 2017
Actual Primary Completion Date December 2, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) Performance status of ≤ 2 (see section 11.1, Appendix A)
  • Histologically confirmed UC of the bladder, urethra, ureter or renal pelvis with Rb+/CDKN2A- based on immunohistochemistry (IHC) of tissue blocks or unstained slides performed within a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory at University of North Carolina (UNC); if stage I of original cohort indicates futility, molecular requirement for eligibility will change to Rb+/CCND1 overexpression (also based on IHC); see statistical section, section 8.0)
  • Metastatic disease that is not amenable to curative surgery or radiation
  • Prior treatment with ≤ two prior cytotoxic regimens; prior therapy must have consisted of at least one of the following: cisplatin, carboplatin, paclitaxel, docetaxel or gemcitabine. If the only prior cytotoxic therapy was administered in the perioperative i.e. neoadjuvant or adjuvant settings, patient is eligible provided the interval from end of therapy to the diagnosis of metastatic disease is less than one year.
  • Progressive disease during or after treatment with at least one of the agents listed above
  • At least one measurable disease site (as defined by Response Evaluation Criteria In Solid Tumors (RECIST)1.1) that has not been previously irradiated
  • No prior therapy with a CDK 4/6 inhibitor; prior anti PD-1 and anti PD-L1 therapy is permitted
  • Washout period should be at least 2 weeks for prior chemotherapy or radiation therapy 3.1.10 Resolution of all acute toxic effects of prior chemotherapy, radiotherapy, surgery to ≤ grade 1 per NCI Common Terminology Criteria for Adverse Events (CTCAE)v4 except neuropathy which may be ≤ grade 2
  • No active brain metastases
  • Adequate bone marrow, liver and renal functions as assessed by the following:

    • Hemoglobin ≥ 8 g/dL;
    • Absolute neutrophil count ≥ 1,500/uL;
    • Platelets ≥ 75,000 g/uL;
    • Total bilirubin ≤ 1.5 times upper limit of normal (ULN);
    • alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times ULN;
    • serum creatinine ≤ 2.5 times ULN;
  • Negative serum pregnancy test in women of child-bearing potential within 7 days of D1 of treatment
  • If fertile, agree to use effective contraception (condom or other barrier methods, oral contraceptives, implantable contraceptives, intrauterine devices) during trial
  • Life expectancy greater than 3 months
  • Subject must be able to give written Institutional Review Board (IRB) approved informed consent and be able to follow protocol requirements

Exclusion Criteria:

  • Any prior treatment with any investigational drug within the preceding 4 weeks
  • Any concurrent active malignancy requiring treatment (other than basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, superficial bladder tumors, other malignancies curatively treated > 3 years prior to study entry) or patients with adenocarcinoma of the prostate that has been surgically treated and with a post-treatment prostate-specific antigen (PSA) that is non-detectable.
  • Unstable systemic disease or active uncontrolled infection
  • Major surgery, open biopsy or significant traumatic injury within 4 weeks prior to study entry
  • Not willing to avoid grapefruit, grapefruit juices, grapefruit hybrids, Seville oranges, pomelos, and exotic citrus fruits from 7 days prior to the dose of study medication and during the entire study due to potential CYP3A4 interaction with the study medication. Orange juice is allowed.
  • Intake of any herbal preparations or medications (including, but not limited to, Saint John's Wort and ginkgo biloba) and dietary supplements within 7 days prior to first dose of study drug
  • Unable or unwilling to discontinue use of any drug known to be a strong or moderate inhibitor or inducer of CYP3A4 (prohibited inducers and inhibitors must be discontinued within 2 weeks prior to first dose of study drug; see section 11.2 Appendix B); unable or unwilling to discontinue use of any proton pump inhibitor; see section 11.2, Appendix B
  • Any malabsorption problem that, in the investigator's opinion, would prevent adequate absorption of the study drug
  • Inability to swallow oral medications
  • Pregnant or breast-feeding
  • Substance abuse, or medical, psychological or social conditions that may interfere with the patient's participation in the study or the evaluation of the study results
  • Other serious, ongoing, non-malignant disease or infection that would compromise protocol objectives
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02334527
Other Study ID Numbers  ICMJE LCCC 1406
14-2196 ( Other Identifier: UNC IRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party UNC Lineberger Comprehensive Cancer Center
Study Sponsor  ICMJE UNC Lineberger Comprehensive Cancer Center
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator: Matthew I Milowsky, MD UNC Lineberger Comprehensive Cancer Center
PRS Account UNC Lineberger Comprehensive Cancer Center
Verification Date November 2018

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