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

NCT02334527 | Terminated Phase 2 Results DMC

• 2 other identifiers: LCCC 140614-2196
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

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.

Conditions

Metastatic Urothelial Carcinoma (UC)

Keywords

metastatic urothelial carcinoma (UC); LCCC 1406; Lineberger; palbociclib

Outcome Measures

Primary Outcomes (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.

  4 Months

Secondary Outcomes (4)

• Progression Free Survival (PFS)

  4 Months

• Overall Survival (OS)

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

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

  4 Months

• Number of Participants With Adverse Events

  30 Days

Study Arms (1)

Palbociclib Single Arm trial

OTHER

Palbociclib

Drug: Palbociclib

Interventions

Palbociclib DRUG

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

Also known as: PD-0332991

Palbociclib Single Arm trial

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);

You may not qualify if:

• 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

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Pfizer: collaborator

Study Sites (3)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

North Carolina Cancer Hospital (UNC)

Chapel Hill, North Carolina, 27599, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Related Links

• Lineberger Comprehensive Cancer Center

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

palbociclib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Robin V. Johnson
• Organization: UNC Lineberger Comprehensive Cancer Center

Robin_V_Johnson@med.unc.edu

919-966-1125

Study Officials

• Matthew I Milowsky, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2015
• First Posted: January 8, 2015
• Study Start: March 17, 2015
• Primary Completion: December 2, 2016
• Study Completion: September 28, 2017
• Last Updated: November 16, 2018
• Results First Posted: April 24, 2018

Record last verified: 2018-11

Locations

US (3)