Testing the PD-1 Inhibitor Pembrolizumab as Maintenance Therapy After Initial Chemotherapy in Metastatic Bladder Cancer



Status:Active, not recruiting
Conditions:Prostate Cancer, Cancer, Cancer, Cancer, Bladder Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:12/12/2018
Start Date:November 2015
End Date:November 2019

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A Randomized, Double-blinded, Phase II Study of Maintenance Pembrolizumab Versus Placebo After First-Line Chemotherapy in Patients With Metastatic Urothelial Cancer: Hoosier Cancer Research Network GU14-182

This is a multi-institutional, randomized, placebo controlled, double-blinded phase II trial
of maintenance pembrolizumab versus placebo after first-line chemotherapy in patients with
metastatic urothelial cancer who have achieved at least stable disease on first-line
chemotherapy.

OUTLINE: This is a multi-center trial.

Eligible subjects will be 1:1 randomized to placebo (Control Arm A) and pembrolizumab
(Experimental Arm B). Stratification factors for randomization: presence of visceral
metastatic disease (lung, liver, or bone or other organs vs. lymph node only) at the time of
initiation of first-line chemotherapy, and response to first-line chemotherapy (CR/PR vs. SD.
Subjects who progress on placebo will be assessed to determine if they are eligible to cross
over to unblinded treatment with pembrolizumab.

INVESTIGATIONAL TREATMENT:

For Control Arm A, commercially available normal saline will be used as the placebo. No
active placebo drug will be mixed with the normal saline.

For Experimental Arm B, pembrolizumab (or placebo), 200 mg intravenous infusion (IV) every 3
weeks for up to 12 months, or until progressive disease (PD) or unacceptable toxicity.

The following required laboratory values must be obtained within fourteen days prior to
registration for protocol therapy:

Hematopoietic:

- Absolute neutrophil count (ANC) ≥1,500 /mcL

- Platelets ≥100,000 / mcL

- Hemoglobin ≥8.5 g/dL

Renal:

- Creatinine ≤1.5x ULN OR

- Measured or calculated creatinine clearance ≥30 mL/min for subject with creatinine
levels >1.5x institutional ULN

- GFR can also be used in place of creatinine or CrCl

Hepatic:

- Serum total bilirubin ≤ 1.5 X ULN OR

- Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN

- AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subject with liver metastases

Coagulation:

- International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN. If subject is
on anticoagulant therapy, PT or PTT must be within therapeutic range of intended use of
anticoagulants.

Inclusion Criteria:

- Written informed consent and HIPAA authorization for release of personal health
information. NOTE: HIPAA authorization may be included in the informed consent or
obtained separately.

- Age ≥ 18 years at the time of consent.

- ECOG Performance Status (PS) of ≤ 1 within fourteen days of registration for protocol
therapy.

- Histological or cytological evidence of urothelial cancer of the bladder, urethra,
ureter, or renal pelvis. Differentiation with variant histologies (e.g., squamous cell
differentiated) will be permitted provided that the predominant histology is
urothelial carcinoma.

- Metastatic and/or unresectable (cT4b) disease

- Must have achieved an objective response (CR/PR) or stable disease (SD) after 4 to 6
cycles of standard first-line platinum-based chemotherapy for mUC (e.g., as per NCCN
guidelines). Able to commence study treatment within 2 to 6 weeks of receiving last
dose of first-line chemotherapy.

- All subjects must have adequate archival tissue available prior to registration (i.e.,
at least 20 unstained slides or paraffin block). If acceptable archival tissue is not
available, the subject must be willing to consent to providing a core or excisional
biopsy for research prior to registration for protocol therapy. If archival tissue is
not available and there are no sites amenable to biopsy, enrollment must be discussed
with the sponsor-investigator on a case by case basis.

- Female subjects of childbearing potential must have a negative serum pregnancy within
three days prior to registration for protocol therapy

- Sexually active, pre-menopausal women of childbearing potential must be willing to use
an adequate method of contraception or be surgically sterile, or abstain from
heterosexual activity for the course of the study through 120 days after the last dose
of study drug. Subjects of childbearing potential are those who have not been
surgically sterilized or have not been free from menses for > one year.

- Male subjects of childbearing potential must agree to use an adequate method of
contraception starting with the first dose of study drug through 120 days after the
last dose of study drug.

Exclusion Criteria:

- More than one line of prior chemotherapy for metastatic or locally advanced disease,
with the following exception:

- Prior neoadjuvant/adjuvant chemotherapy will not count as line of therapy if
completed greater than 12 months prior to initiation of chemotherapy regimen for
metastatic or unresectable disease.

- Current or past participation in a study of an investigational agent or using an
investigational device within four weeks of registration for protocol therapy.

- A diagnosis of immunodeficiency or is receiving treatment with systemic steroid
therapy or any other form of immunosuppressive therapy within seven days prior to
registration for protocol therapy.

- Prior chemotherapy, targeted small molecule therapy, or radiation therapy within two
weeks prior to registration for protocol therapy. Note: If the subjects have undergone
major surgery, they must have recovered adequately from the toxicity and/or
complications from the intervention prior to starting protocol therapy.

- A known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
skin, or in situ cervical cancer that has undergone potentially curative therapy.

- A 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 registration for protocol therapy 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 seven days prior to registration for protocol therapy.

- Active autoimmune disease that has required systemic treatment in 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.

- Has evidence of active, non-infectious pneumonitis.

- Has a history of interstitial lung disease.

- An active infection requiring systemic therapy.

- A 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.

- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening period through 120 days
after the last dose of protocol therapy.

- Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic
T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other
antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
Examples include nivolumab, MPDL3280, etc.

- A known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

- A known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).

- Receipt of a live vaccine within 30 days prior to registration for protocol therapy.

- Unresolved toxicity (i.e., > Grade 1 or above baseline) due to previously administered
agents. Exception includes: subjects with ≤ Grade 2 neuropathy are eligible for the
study.
We found this trial at
28
sites
601 Elmwood Avenue
Rochester, New York 14642
(585) 275-2100
Principal Investigator: Elizabeth Guancial, MD
Phone: 585-275-3351
Univ of Rochester Medical Center One of the nation's top academic medical centers, the University...
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1201 Camino de Salud Northeast
Albuquerque, New Mexico 87131
(505) 272-4946
Principal Investigator: Richard Lauer, MD
Phone: 505-925-0390
University of New Mexico Cancer Center It’s been 40 years since the New Mexico State...
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Albuquerque, NM
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Baltimore, Maryland 21231
410-955-6190
Phone: 443-287-2886
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins The name Johns Hopkins has become synonymous...
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Baltimore, MD
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666 Elm Street
Buffalo, New York 14263
(716) 845-2300
Phone: 716-845-3880
Roswell Park Cancer Institute Welcome to Roswell Park Cancer Institute (RPCI), America's first cancer center...
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Buffalo, NY
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Chapel Hill, North Carolina 27599
(919) 962-2211
Principal Investigator: Matthew Milowsky, MD
Phone: 919-843-3406
University of North Carolina at Chapel Hill Carolina’s vibrant people and programs attest to the...
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Chapel Hill, NC
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1500 E Duarte Rd
Duarte, California 91010
(626) 256-4673
Phone: 626-256-4673
City of Hope Comprehensive Cancer Center City of Hope is a leading research and treatment...
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Duarte, CA
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Gainesville, Florida 32610
(352) 392-3261
Phone: 352-273-9094
University of Florida The University of Florida (UF) is a major, public, comprehensive, land-grant, research...
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Gainesville, FL
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Los Angeles, California 90033
213) 740-2311
Principal Investigator: David Quinn, MD
Phone: 323-865-0843
University of Southern California The University of Southern California is one of the world’s leading...
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Los Angeles, CA
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Minneapolis, Minnesota 55455
(612) 625-5000
Principal Investigator: Shilpa Gupta, MBBS
Phone: 612-625-0761
Univ of Minnesota With a flagship campus in the heart of the Twin Cities, and...
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2220 Pierce Ave
Nashville, Tennessee 37232
615-936-8422
Principal Investigator: David D Chism, MD
Phone: 615-875-7172
Vanderbilt-Ingram Cancer Center The Vanderbilt-Ingram Cancer Center, located in Nashville, Tenn., brings together the clinical...
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Baltimore, Maryland 20742
(301) 405-1000
Principal Investigator: Arif Hussain, MD
Phone: 410-328-5697
University of Maryland As a globally-connected university offering a world-class education, the University of Maryland...
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171 Ashley Avenue
Charleston, South Carolina 29425
843-792-1414
Principal Investigator: Theodore Gourdin, MD
Phone: 843-792-0585
Medical University of South Carolina The Medical University of South Carolina (MUSC) has grown from...
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Columbus, Ohio 43210
Principal Investigator: Amir Mortazavi, MD
Phone: 614-688-8836
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Detroit, Michigan 48202
Principal Investigator: Clara Hwang, MD
Phone: 313-916-9417
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Goshen, Indiana 46526
Phone: 574-364-2888
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Hackensack, New Jersey 07601
Phone: 551-996-5900
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535 Barnhill Dr
Indianapolis, Indiana 46202
(888) 600-4822
Phone: 317-278-1711
Indiana University Melvin and Bren Simon Cancer Center At the IU Simon Cancer Center, more...
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Indianapolis, IN
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6845 Rama Drive
Indianapolis, Indiana 46219
Phone: 317-859-5500
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Indianapolis, Indiana 46256
Principal Investigator: Radhika Walling, MD
Phone: 317-621-4290
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Munster, Indiana 46321
Phone: 219-852-6456
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New York, New York 10029
Phone: 212-241-8214
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5900 Lake Wright Dr
Norfolk, Virginia 23502
(757) 466-8683
Phone: 757-213-5813
Virginia Oncology Associates Virginia Oncology Associates is an oncology and hematology practice of physicians, specializing...
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Norfolk, VA
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17607 Gold Plaza
Omaha, Nebraska 68130
Principal Investigator: Luke Nordquist, MD
Phone: 402-991-8468
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Omaha, NE
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Philadelphia, Pennsylvania 19111
Principal Investigator: Daniel Geynisman, MD
Phone: 215-728-7413
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625 North 6th Street
Phoenix, Arizona 85004
Principal Investigator: Jue Wang, MD
Phone: 602-827-2683
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4960 Childrens Place
Saint Louis, Missouri 63110
Phone: 314-362-5740
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2000 Circle of Hope Dr
Salt Lake City, Utah 84112
(801) 585-0303
Huntsman Cancer Institute at University of Utah Huntsman Cancer Institute (HCI) is part of the...
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3700 O St NW
Washington, District of Columbia 20057
(202) 687-0100
Principal Investigator: George Phillips, MD
Phone: 202-687-4415
Georgetown University Georgetown University is one of the world's leading academic and research institutions, offering...
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