Paclitaxel and Pembrolizumab in Treating Patients With Refractory Metastatic Urothelial Cancer
Single-Arm Phase II Combination Study of Low-Dose Paclitaxel With Pembrolizumab in Platinum-Refractory Urothelial Carcinoma
4 other identifiers
interventional
27
1 country
1
Brief Summary
This phase II trial studies how well paclitaxel and pembrolizumab works in treating patients with urothelial cancer that has not responded to previous treatment and has spread to other places in the body. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving paclitaxel together with pembrolizumab may be an effective treatment for urothelial cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Apr 2016
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 13, 2015
CompletedFirst Posted
Study publicly available on registry
October 21, 2015
CompletedStudy Start
First participant enrolled
April 6, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 11, 2021
CompletedResults Posted
Study results publicly available
October 5, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
December 19, 2022
CompletedJanuary 10, 2023
January 1, 2023
5.1 years
October 13, 2015
July 21, 2022
January 6, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Response Rate
The overall response rate will be performed in all patients that are evaluable for efficacy and will have one interim analysis. Overall response is complete response (CR) = Disappearance of all target lesions (PR) = at least a 30% decrease in sum of diameters, taking as reference the baseline sum diameters; stable disease (SD) = neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum diameters while on study; and progressive disease (PD) = at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study based on all target lesions recorded since the treatment started.
Up to 6 months
Secondary Outcomes (2)
Number of Adverse Events Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Up to 1 year
Progression Free Survival (Kaplan Meier Method)
At 6 months
Study Arms (1)
Treatment (pembrolizumab, paclitaxel)
EXPERIMENTALPatients receive pembrolizumab IV over 30 minutes on day 1 and paclitaxel IV over 60 minutes on day 1 and 8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Patients diagnosed with platinum-refractory metastatic urothelial cancer that is measureable based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1.36 Platinum-refractory disease is defined as progressive disease on cisplatin or carboplatin therapy or within 12 months of prior platinum treatment (last dose.)
- At least 1 prior chemotherapy regimen containing cisplatin or carboplatin
- Patient must be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 months (168 days) prior to initiation of treatment on Day 1. Archived specimen can be used for subjects, if available
- Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
- Adequate organ function as defined below:
- Absolute neutrophil count (ANC) \>= 1,500 /mcL
- Platelets \>= 80,000 / mcL
- Hemoglobin \>= 9 g/dL without transfusion dependency
- Serum creatinine =\< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance rate \[CrCl\]) \>= 35 mL/min for subject with creatinine levels \> 1.5 X institutional ULN
- Serum total bilirubin =\< 1.5 X ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X ULN OR =\< 5 X ULN for subjects with liver metastases
- Albumin \>= 2.5 mg/dL
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
- +1 more criteria
You may not qualify if:
- Currently receiving or has had treatment with an investigational agent or used an investigational device within 4 weeks of study day 1
- Anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
- Chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent
- Note: Subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study
- Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- Prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death-ligand 1 (PD-L1), or anti-programmed cell death-ligand 2 (PD-L2) agent. Prior therapy with paclitaxel or docetaxel
- Hypersensitivity to pembrolizumab, any of its excipients, paclitaxel, or any of its excipients
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Known history of active TB (Bacillus tuberculosis)
- Known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Known history of, or any evidence of active, non-infectious pneumonitis
- Active infection requiring systemic therapy
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Principal Investigator
- Organization
- Wake Forest Baptist Comprehensive Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Michael Goodman, MD
Wake Forest University Health Sciences
Publication Agreements
- PI is Sponsor Employee
- 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
October 13, 2015
First Posted
October 21, 2015
Study Start
April 6, 2016
Primary Completion
May 11, 2021
Study Completion
December 19, 2022
Last Updated
January 10, 2023
Results First Posted
October 5, 2022
Record last verified: 2023-01