Clinical Trials /

Paclitaxel and Pembrolizumab in Treating Patients With Refractory Metastatic Urothelial Cancer

NCT02581982

Description:

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.

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Paclitaxel and Pembrolizumab in Treating Patients With Refractory Metastatic Urothelial Cancer
  • Official Title: Single-Arm Phase II Combination Study of Low-Dose Paclitaxel With Pembrolizumab in Platinum-Refractory Urothelial Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: IRB00035397
  • SECONDARY ID: NCI-2015-01713
  • SECONDARY ID: CCCWFU 88215
  • SECONDARY ID: P30CA012197
  • NCT ID: NCT02581982

Conditions

  • Transitional Cell Carcinoma

Interventions

DrugSynonymsArms
PaclitaxelAnzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol KonzentratTreatment (pembrolizumab, paclitaxel)
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (pembrolizumab, paclitaxel)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
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.
  • Paclitaxel
  • Pembrolizumab

Eligibility 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

          -  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 12
             weeks (84 days) prior to initiation of treatment on day 1; archived specimen can be
             used for subjects in whom newly-obtained samples cannot be provided

          -  Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             performance scale

          -  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

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate
Time Frame:Up to 6 months
Safety Issue:
Description:The overall response rate will be performed in all patients that are evaluable for efficacy and will have one interim analysis.

Secondary Outcome Measures

Measure: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
Safety Issue:
Description: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.
Measure:Progression Free Survival
Time Frame:At 6 months
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Wake Forest University Health Sciences

Trial Keywords

  • Urothelial cancer
  • Bladder cancer
  • Immunotherapy
  • Paclitaxel

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