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Paclitaxel and Pembrolizumab in Treating Patients With Refractory Metastatic Urothelial Cancer

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: NCT02581982
Recruitment Status : Active, not recruiting
First Posted : October 21, 2015
Last Update Posted : September 1, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Wake Forest University Health Sciences

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.

Condition or disease Intervention/treatment Phase
Transitional Cell Carcinoma Other: Laboratory Biomarker Analysis Drug: Paclitaxel Biological: Pembrolizumab Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To estimate the overall response rate (ORR) of pembrolizumab combined with paclitaxel.

SECONDARY OBJECTIVES:

I. To determine the safety and tolerability of pembrolizumab combined with paclitaxel.

II. To calculate the progression-free survival (PFS) rate at 6 months.

TERTIARY OBJECTIVES:

I. To determine the immune effects of pembrolizumab combined with paclitaxel. II. To associate immune effects with tumor response. III. To explore changes in immune-regulatory micro ribonucleic acids (RNAs) as biomarkers of response.

OUTLINE:

Patients receive pembrolizumab intravenously (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.

After completion of study treatment, patients are followed up within 30 days and then every 3 months for 1 year.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Single-Arm Phase II Combination Study of Low-Dose Paclitaxel With Pembrolizumab in Platinum-Refractory Urothelial Carcinoma
Actual Study Start Date : April 6, 2016
Actual Primary Completion Date : May 11, 2021
Estimated Study Completion Date : August 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (pembrolizumab, paclitaxel)
Patients 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.
Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475




Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: Up to 6 months ]
    The overall response rate will be performed in all patients that are evaluable for efficacy and will have one interim analysis.


Secondary Outcome Measures :
  1. Incidence of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 1 year ]
    All adverse events will be tabulated and presented by preferred term and/or system organ class and grade. All deaths and serious adverse events will be tabulated.

  2. Progression Free Survival [ Time Frame: At 6 months ]
    The Kaplan Meier methods will be used to estimate progression free survival. The 6-month PFS will be compared to historical rates using a chi-square test.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document

Exclusion Criteria:

  • 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
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Pregnancy or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Known active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Received a live vaccine within 30 days of planned start of study therapy

    • Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02581982


Locations
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United States, North Carolina
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
Sponsors and Collaborators
Wake Forest University Health Sciences
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Michael Goodman, MD Wake Forest University Health Sciences
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Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT02581982    
Other Study ID Numbers: IRB00035397
NCI-2015-01713 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CCCWFU 88215 ( Other Identifier: Wake Forest University Health Sciences )
P30CA012197 ( U.S. NIH Grant/Contract )
First Posted: October 21, 2015    Key Record Dates
Last Update Posted: September 1, 2021
Last Verified: August 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Wake Forest University Health Sciences:
Urothelial cancer
Bladder cancer
Immunotherapy
Paclitaxel
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Paclitaxel
Pembrolizumab
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological