Neoplasms

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Recurrence

Urinary Bladder Neoplasms

Carcinoma, Transitional Cell

Urethral Neoplasms

Kidney Neoplasms

Ureteral Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urethral Diseases

Urologic Diseases

Male Urogenital Diseases

Urinary Bladder Diseases

Kidney Diseases

Ureteral Diseases

Transitional Cell Carcinoma

Urethral Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Pembrolizumab

Docetaxel

Antimetabolites

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

pembrolizumab IV over 30 minutes on day 1 and docetaxel IV over 60 minutes on day 1.

pembrolizumab IV as in Arm A and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8.

Gemcitabine Hydrochloride

Primo Lara

This phase I trial studies the side effects and best dose of pembrolizumab when given together with docetaxel or gemcitabine hydrochloride in treating patients with previously treated urothelial cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) or that has spread from the primary site (place where it started) to other places in the body (metastatic). Monoclonal antibodies, such as pembrolizumab, may block tumor growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as docetaxel and gemcitabine hydrochloride, 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. Giving pembrolizumab together with docetaxel or gemcitabine hydrochloride may be a better treatment for urothelial cancer.

PRIMARY OBJECTIVES:

I. To evaluate the safety and tolerability of MK-3475 (pembrolizumab) when given in combination with docetaxel or gemcitabine (gemcitabine hydrochloride) in patients with advanced or metastatic platinum-treated urothelial cancer.

SECONDARY OBJECTIVES:

I. To assess in a preliminary manner the efficacy of this combination (overall response rate and progression free survival).

II. To determine in an exploratory manner programmed death (PD)-ligand (L)1 expression in archival tumor specimens and to correlate this with patient outcomes.

OUTLINE: This is a dose-escalation study of pembrolizumab. Patients are assigned to 1 of 2 treatment arms. (Patients who had received prior gemcitabine hydrochloride/cisplatin or gemcitabine hydrochloride/carboplatin \[GC\] or methotrexate, vinblastine sulfate, adriamycin, and cisplatin \[MVAC\] therapy are assigned to Arm A).

ARM A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and docetaxel IV over 60 minutes on day 1.

ARM B: Patients receive pembrolizumab IV as in Arm A and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8.

In both arms, treatment repeats every 21 days for 12 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 6 months.

Pembrolizumab and Docetaxel or Gemcitabine Hydrochloride in Treating Patients Urothelial Cancer

Feasibility Trial of MK3475 + Docetaxel or Gemcitabine in Platinum Pre-treated Urothelial Cancer

Will be summarized descriptively by tables of numbers and percent of patients experiencing adverse events, overall and by type, grade, seriousness, duration, action taken, and assessment of relation to pembrolizumab or docetaxel or gemcitabine hydrochloride.

The number and proportion experiencing complete response, partial response, stable disease, or progressive disease will be summarized separately for each study arm.

Will be summarized graphically by Kaplan-Meier curves and descriptively by a corresponding life-table approach to allow for possible censored data.

The relation of PD-L1 expression at baseline to outcome (ORR and PFS) will be summarized descriptively in exploratory analyses, separately for each study arm. Descriptive associations with ORR will be summarized by the means and standard deviations for responders vs. non-responders, and graphically by dot plots of PD-L1 expression for responders and non-responders. Descriptive associations with PFS will be summarized by Kaplan-Meier plots comparing PFS for high and low PD-L1 expression.

Merck Sharp & Dohme LLC

University of California, Davis

Antibodies

Sacituzumab govitecan

Immunoglobulins

Immunoconjugates

Immunologic Factors

Participants will be given the study drugs Enfortumab Vedotin and then Sacituzumab Govitecan on Days 1 and 8 of a 21-day study cycle. Dose escalation and de-escalation for the Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV) combination will be guided using the Bayesian optimal interval (BOIN) design with up to 4 dose level escalations.

Sacituzumab Govitecan (SG)

Enfortumab vedotin-ejfv (EV)

Bradley A McGregor, MD

This research study will assess what doses of Sacituzumab Govitecan and Enfortumab Vedotin can be safely combined in the treatment of metastatic urothelial carcinoma (mUC).

The names of the study drugs in this investigational combination are:

* Enfortumab Vedotin
* Sacituzumab Govitecan

This study is a single-center, open-label, nonrandomized phase I trial testing the safety and efficacy as well as defining the appropriate dose for future studies of Sacituzumab Govitecan and Enfortumab for people with metastatic urothelial carcinoma (mUC) progressing on platinum-based chemotherapy and PD1/L1 inhibitors

The U.S. Food and Drug Administration (FDA) has approved Enfortumab Vedotin for the treatment of metastatic urothelial carcinoma (mUC) (bladder cancer). The FDA has not approved Sacituzumab Govitecan for metastatic urothelial carcinoma (mUC) (bladder cancer) but it has been approved for other uses. The FDA has approved Sacituzumab Govitecan to treat a type of breast cancer at this time. Sacituzumab Govitecan has appeared promising in patients with bladder cancer that has spread and works by a different mechanism than Enfortumab Vedotin. Therefore, the researchers believe that combining these 2 drugs may control the cancer better than each drug does on its own.

This will be done through testing different combinations and checking for serious side effects; if there are no serious side effects a different dose combination will be explored. Once the best combination has been determined, the study will look to see how effective (how well the drug works) it is in slowing down the growth of metastatic urothelial carcinoma (mUC) progressing on platinum-based chemotherapy and PD1/L1 inhibitors and define the most appropriate level of the drugs to use for further studies.

The research study procedures include screening for eligibility, study treatment, and safety follow-up visits, in addition to general health status follow-up after study treatment.

Participants will receive study treatment for as long as they do not have serious side effects and their disease does not get worse. However, the duration may vary depending on how long the treatment works to control the cancer and how someone's body tolerates the side effects.

Immunomedics, a pharmaceutical company, is supporting this research study by providing funding for the research study, tests required for research purposes only, and the study drug Sacituzumab Govitecan.

It is expected that up to 24 people will take part in this research study.

Sacituzumab Govitecan Plus EV in Metastatic UC

Sacituzumab Govitecan Plus Enfortumab Vedotin for Metastatic Urothelial Carcinoma Progressing on Platinum-based Chemotherapy and PD1/L1 Inhibitors: the Double Antibody Drug Conjugate (DAD) Phase I Trial

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

The Maximum Tolerated Dose (MTD) in mg of Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV) in Combination is assessed.

Treatment-Related Adverse Events are assessed by CTCAE v5.0 when administering Sacituzumab Govitecan (SG) and Enfortumab Vedotin (EV) in combination.

Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pembrolizumab and Docetaxel or Gemcitabine Hydrochloride in Treating Patients Urothelial Cancer	NCT02437370	Metastatic Urot... Recurrent Bladd... Recurrent Uroth... Regional Urothe... Stage III Bladd... Stage III Ureth... Stage IV Bladde... Stage IV Urethr... Urethral Urothe...	Pembrolizumab Docetaxel Gemcitabine Hyd...	18 Years -	University of California, Davis
Sacituzumab Govitecan Plus EV in Metastatic UC	NCT04724018	Urothelial Canc... Metastatic Urot... Metastatic Urot... Bladder Cancer	Sacituzumab Gov... Enfortumab vedo...	18 Years -	Dana-Farber Cancer Institute
Pembrolizumab and Docetaxel or Gemcitabine Hydrochloride in Treating Patients Urothelial Cancer	NCT02437370	Metastatic Urot... Recurrent Bladd... Recurrent Uroth... Regional Urothe... Stage III Bladd... Stage III Ureth... Stage IV Bladde... Stage IV Urethr... Urethral Urothe...	Pembrolizumab Docetaxel Gemcitabine Hyd...	18 Years -	University of California, Davis
Pembrolizumab and Docetaxel or Gemcitabine Hydrochloride in Treating Patients Urothelial Cancer	NCT02437370	Metastatic Urot... Recurrent Bladd... Recurrent Uroth... Regional Urothe... Stage III Bladd... Stage III Ureth... Stage IV Bladde... Stage IV Urethr... Urethral Urothe...	Pembrolizumab Docetaxel Gemcitabine Hyd...	18 Years -	University of California, Davis

Spots Global Cancer Trial Database for metastatic urothelial carcinoma of the renal pelvis and ureter