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BRIEF TITLE: Study of Maintenance Pembrolizumab Versus Placebo After First-Line Chemotherapy in Patients With Metastatic Urothelial Cancer: Hoosier Cancer Research Network GU14-182

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


  • Org Study ID: HCRN GU14-182
  • Secondary ID:
  • NCT ID: NCT02500121
  • NCT Alias:
  • Sponsor: Matthew Galsky - Other
  • Source: Hoosier Cancer Research Network

Brief Summary

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.

Detailed Description


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.

Overal Status Start Date Phase Study Type
Recruiting Start Date: November 2015 Phase 2 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Six-month progression-free survival (PFS) disease assessment among subjects treated with pembrolizumab versus placebo as maintenance therapy after up to 8 cycles of first-line chemotherapy.

Primary Outcome 1 - Time Frame: Assessed at six months, calculated from the date of randomization

Condition:

  • Urothelial Carcinoma
  • Bladder Cancer

Eligibility

Criteria:
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.
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Matthew Galsky, M.D.

Role: Study Chair

Affiliation: Hoosier Cancer Research Network

Overall Contact

Name: Matthew Galsky, M.D.

Phone: 212.241.6756

Email: matthew.galsky@mssm.edu

Link: Hoosier Cancer Research Network Website

Locations

Facility Status Contact
University of Arizona at Dignity Health St. Joseph's
Phoenix, Arizona 85004
United States
Recruiting Brent Freeman
602-827-2683
brentfreeman@email.arizona.edu
City of Hope Comprehensive Cancer Center
Duarte, California 91010
United States
Recruiting Sumanta K Pal, MD
626-256-4673
University of Southern California
Los Angeles, California 90033
United States
Recruiting Taison Tran
323-865-0843
Taison.Tran@med.usc.edu
Georgetown University
Washington, District of Columbia 20057
United States
Recruiting Tiffany Swaringer
202-687-4415
tls35@georgetown.edu
University of Florida
Gainesville, Florida 32610
United States
Recruiting Long H Dang, MD
352-273-9094
IU Health Goshen Center for Cancer Care
Goshen, Indiana 46526
United States
Recruiting Sachin Agarwal, MD
574-364-2888
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana 46202
United States
Recruiting Costantine Albany, MD
317-278-1711
IU Health Central Indiana Cancer Center
Indianapolis, Indiana 46219
United States
Recruiting Madelaine Sgroi, MD
317-859-5500
Community Regional Cancer Care
Indianapolis, Indiana 46256
United States
Recruiting Kathy Tudor
317-621-4290
ktudor@ecommunity.com
Community Healthcare System
Munster, Indiana 46321
United States
Recruiting Edwin Robin, M.D.
219-852-6456
erobin@comhs.org
University of Maryland
Baltimore, Maryland 21201
United States
Recruiting Amelia Schmidt
410-328-5697
ameliaSchmidt@umm.edu
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland 21231
United States
Recruiting Noah Hahn, MD
443-287-2886
Henry Ford Health System
Detroit, Michigan 48202
United States
Recruiting Travis Wheeler
313-916-9417
twheele1@hfhs.org
University of Minnesota
Minneapolis, Minnesota 55455
United States
Recruiting Julie Madsen
612-625-0761
mads0056@umn.edu
Washington University: Siteman Cancer Center
Saint Louis, Missouri 63110
United States
Recruiting Joel Picus, M.D.
314-362-5740
jpicus@dom.wustl.edu
GU Cancer Research Network, LLC
Omaha, Nebraska 68130
United States
Recruiting Diane Tichota
402-991-8468
dtichota@gucancer.com
The John Theuer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey 07601
United States
Recruiting Robert Alter, MD
551-996-5900
University of New Mexico Cancer Center
Albuquerque, New Mexico 87106
United States
Recruiting Valerie Parks
505-925-0390
vparks@salud.unm.edu
Roswell Park Cancer Institute
Buffalo, New York 14263
United States
Recruiting Saby George, MD
716-845-3880
Tisch Cancer Institute at Mount Sinai Medical Center
New York, New York 10029
United States
Recruiting Matthew Galsky, M.D.
212-241-8214
matthew.galsky@mssm.edu
University of Rochester Medical Center
Rochester, New York 14642
United States
Recruiting Ayesha Khan
585-275-3351
Ayesha_khan@urmc.rochester.edu
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina 27514
United States
Recruiting Max Perlmutt
919-843-3406
max_perlmutt@med.unc.edu
Ohio State University Comprehensive Cancer Center
Columbus, Ohio 43210
United States
Recruiting Tiffany Lancaster
614-688-8836
tiffany.lancaster@osumc.edu
Fox Chase Cancer Center
Philadelphia, Pennsylvania 19111
United States
Recruiting Marla Jones
215-728-7413
Marla.Jones@fccc.edu
Medical University of South Carolina
Charleston, South Carolina 29425
United States
Recruiting Ryan Smiley
843-792-0585
smiler@musc.edu
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee 37232
United States
Recruiting Deepa Arun
615-875-7172
deepa.arun@Vanderbilt.Edu
Huntsman Cancer Institute University of Utah
Salt Lake City, Utah 84112
United States
Recruiting Sumati V Gupta, MD

Virginia Oncology Associates
Norfolk, Virginia 23502
United States
Recruiting Mark Fleming, M.D.
757-213-5813
mark.fleming@usoncology.com