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Metastatic Urothelial Carcinoma (UC)Phase 2NCT02334527

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

A Phase 2 study testing Palbociclib in people with Metastatic Urothelial Carcinoma (UC), run by UNC Lineberger Comprehensive Cancer Center at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Urothelial Carcinoma (UC)
What is being tested?
Palbociclib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
3 sitesUnited States
Study dates
17 Mar 2015to 28 Sep 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • North Carolina Cancer Hospital (UNC)

    Chapel Hill, North Carolina, 27599

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232

Other trials in United States

About this study

Official title: Phase II Trial of Palbociclib (PD-0332991) in Patients With Metastatic Urothelial Cancer (UC) After Failure of First-Line Chemotherapy

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.

Read the 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.

Being tested
Palbociclib
Keywords
metastatic urothelial carcinoma (UC), LCCC 1406, Lineberger, palbociclib
Medical subject headings
Carcinoma, Transitional Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PalbociclibDrug

    Also called PD-0332991

    125 mg capsule will be taken once per day orally and continuously for 3 weeks followed by 1 week off.

Study groups in NCT02334527
Study groupRoleWhat they receive
Palbociclib Single Arm trialOtherPalbociclib
Receives: Drug: Palbociclib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival

    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.

    Measured: 4 Months

Secondary outcomes (4)

  1. Progression Free Survival (PFS)

    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

    Measured: 4 Months

  2. Overall Survival (OS)

    Overall survival is defined as the time from day 1 of treatment until death as a result of any cause.

    Measured: Patients will be followed for up to 5 years after removal from study therapy or death, whichever occurs first.

  3. Response Rate (RR) - Total Number of Patients With Complete Response (CR) and/or Partial Response (PR)

    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.

    Measured: 4 Months

  4. Number of Participants With Adverse Events

    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.

    Measured: 30 Days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jan 2015 (estimated)
  2. Study start17 Mar 2015
  3. Primary completion2 Dec 2016
  4. Study completion28 Sep 2017

Why it stopped: Data from first 12 subjects-primary endpoint not met. Data analysis underway.

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02334527
Sponsor's protocol ID
LCCC 1406
Other IDs
14-2196
Status last verified
Nov 2018
First submitted
6 Jan 2015
Last updated
16 Nov 2018
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Palbociclib in people with Metastatic Urothelial Carcinoma (UC), run by UNC Lineberger Comprehensive Cancer Center at 3 sites in United States.

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 21 inclusion and 12 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: stopped early, as of the sponsor's last update on 16 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Progression Free Survival (time frame: 4 Months). 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 NCT02334527.

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 16 Nov 2018.

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