Paclitaxel and Pembrolizumab in Treating Patients With Refractory Metastatic Urothelial Cancer

Sponsor

Wake Forest University Health Sciences (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02581982

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

75.8

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

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:

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

SECONDARY OBJECTIVES:

To determine the safety and tolerability of pembrolizumab combined with paclitaxel.
To calculate the progression-free survival (PFS) rate at 6 months.

TERTIARY OBJECTIVES:

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.

Study Design

Study Type:

Interventional

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 :

Apr 6, 2016

Actual Primary Completion Date :

May 11, 2021

Anticipated Study Completion Date :

Aug 1, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Overall Response Rate [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

Incidence of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [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.
Progression Free Survival [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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