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Metastatic Bladder Urothelial CarcinomaPhase 2NCT02567409

Cisplatin and Gemcitabine Hydrochloride With or Without Berzosertib in Treating Patients With Metastatic Urothelial Cancer

A Phase 2 study testing Berzosertib, Cisplatin and Gemcitabine Hydrochloride in people with Metastatic Bladder Urothelial Carcinoma and Metastatic Renal Pelvis and Ureter Urothelial Carcinoma, run by National Cancer Institute (NCI) at 39 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase II trial studies how well cisplatin and gemcitabine hydrochloride with or without berzosertib works in treating patients with urothelial cancer that has spread to other places in the body (metastatic). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Berzosertib, Cisplatin and Gemcitabine Hydrochloride
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
87 participants
Where
39 sitesUnited States
Study dates
31 Jan 2017to 25 Apr 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically or cytologically confirmed metastatic urothelial carcinoma; urothelial cancer derived from the bladder, ureter or upper tract is permitted
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) with conventional techniques or as >= 10 mm (>= 1 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
  • Patients must have access to archival tumor tissue for proposed correlative studies; these may be derived from transurethral resection of bladder tumors (TURBT), cystectomy, or biopsy; if archival tissue is not available for proposed correlatives, patients may be enrolled at the discretion of the study principal investigator (PI) (SKP)
  • No prior cytotoxic chemotherapy for metastatic disease; prior immunotherapy is permitted
  • At least 12 months have elapsed since platinum-based peri-operative treatment
  • Karnofsky >= 70% (Eastern Cooperative Oncology Group [ECOG] performance status 0-1)
Show all 15Show fewer
  • Life expectancy of greater than 3 months
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin within institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Creatinine clearance >= 50 mL/min by either measured (using the Cockcroft-Gault, Modification of Diet in Renal Disease [MDRD] or Chronic Kidney Disease Epidemiology [CKD-EPI] formula) or calculated clearance (i.e. glomerular filtration rate [GFR])
  • The effects of M6620 (VX-970) on the developing human fetus are unknown; for this reason and because DNA-damage response (DDR) inhibitors as well as other therapeutic agents used in this trial may have teratogenic potential, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of M6620 (VX-970) administration
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Radiotherapy within 4 weeks of protocol therapy
  • Patients who are receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to M6620 (VX970), cisplatin, or gemcitabine
  • M6620 (VX-970) is primarily metabolized by CYP3A4; therefore, concomitant administration with strong inhibitors or inducers of CYP3A4 should be avoided; because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference for a list of drugs to avoid or minimize use of; Patient Drug Information Handout and Wallet Card should be provided to patients; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because M6620 (VX-970) as a DNA-damage response (DDR) inhibitor may have the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M6620 (VX-970), breastfeeding should be discontinued if the mother is treated with M6620 (VX-970); these potential risks may also apply to other agents used in this study
  • Patients with >= grade 2 neuropathy

Trial locations and contacts

39 sites in 1 country.

39 sites in 1 country

United States39 sites

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Nebraska Medicine-Bellevue

    Bellevue, Nebraska, 68123

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • University of Kansas Clinical Research Center

    Fairway, Kansas, 66205

  • Weisberg Cancer Treatment Center

    Farmington Hills, Michigan, 48334

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • Vanderbilt Breast Center at One Hundred Oaks

    Nashville, Tennessee, 37204

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • USC Norris Oncology/Hematology-Newport Beach

    Newport Beach, California, 92663

  • Nebraska Medicine-Village Pointe

    Omaha, Nebraska, 68118

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Stanford Cancer Institute Palo Alto

    Palo Alto, California, 94304

  • Keck Medical Center of USC Pasadena

    Pasadena, California, 91105

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona, 85054

  • University of Pittsburgh Cancer Institute (UPCI)

    Pittsburgh, Pennsylvania, 15232

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

  • Siteman Cancer Center at Christian Hospital

    St Louis, Missouri, 63136

  • University of Kansas Hospital-Westwood Cancer Center

    Westwood, Kansas, 66205

Other trials in United States

About this study

Official title: A Randomized Phase 2 Trial of Cisplatin/Gemcitabine With or Without M6620 (VX-970) in Metastatic Urothelial Carcinoma

This phase II trial studies how well cisplatin and gemcitabine hydrochloride with or without berzosertib works in treating patients with urothelial cancer that has spread to other places in the body (metastatic). Drugs used in chemotherapy, such as cisplatin 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. Berzosertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known if cisplatin and gemcitabine hydrochloride work better alone or with berzosertib in treating patients with urothelial cancer.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine if the addition of berzosertib (M6620 [VX-970]) to cisplatin/gemcitabine hydrochloride (gemcitabine) improves progression-free survival (PFS) relative to cisplatin/gemcitabine alone.

SECONDARY OBJECTIVES:

  1. To compare overall survival (OS) with the addition of M6620 (VX-970) to cisplatin/gemcitabine relative to cisplatin/gemcitabine alone.

II. To compare tumor response rate with the addition of M6620 (VX-970) to cisplatin/gemcitabine relative to cisplatin/gemcitabine alone.

III. To compare safety with the addition of M6620 (VX-970) to cisplatin/gemcitabine relative to cisplatin/gemcitabine alone.

IV. To assess the role of p53 status in predicting response to M6620 (VX-970)-based therapy.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and 8, and cisplatin IV over 60 minutes on day 1. Patients also receive berzosertib IV over 60 minutes on days 2 and 9. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive gemcitabine hydrochloride and cisplatin as in Arm A.

After completion of study treatment, patients are followed up to 36 months.

Being tested
Berzosertib, Cisplatin, Gemcitabine Hydrochloride

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BerzosertibDrug

    Also called 2-Pyrazinamine, 3-(3-(4-((Methylamino)methyl)phenyl)-5-isoxazolyl)-5-(4-((1-methylethyl)sulfonyl)phenyl)-, M 6620, M6620, VX 970

    Given IV

  • CisplatinDrug

    Also called Abiplatin, Blastolem, Briplatin, CDDP

    Given IV

  • Gemcitabine HydrochlorideDrug

    Also called dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemcitabine HCI, Gemzar

    Given IV

Study groups in NCT02567409
Study groupRoleWhat they receive
Arm A (berzosertib, gemcitabine hydrochloride, cisplatin)ExperimentalPatients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and cisplatin IV over 60 minutes on day 1. Patients also receive berzosertib IV over 60 minutes on days 2 and 9. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Berzosertib; Drug: Cisplatin; Drug: Gemcitabine Hydrochloride
Arm B (gemcitabine hydrochloride, cisplatin)ExperimentalPatients receive gemcitabine hydrochloride and cisplatin as in Arm A.
Receives: Drug: Cisplatin; Drug: Gemcitabine Hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS)

    Estimated using the product-limit method of Kaplan and Meier. Event defined as progression or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    Measured: Day of randomization, until progression, or death, assessed up to 12 months

Secondary outcomes (3)

  1. Overall Survival (OS)

    Estimated using the product-limit method of Kaplan and Meier. Event defined as death from any cause.

    Measured: Up to 36 months

  2. Confirmed Objective Response Rate

    Response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Confirmed Objective Response = CR + PR.

    Measured: Up to 36 months

  3. Treatment Limiting Adverse Events

    Adverse events that were fatal or led to treatment discontinuation.

    Measured: Assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 36 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Oct 2015 (estimated)
  2. Study start31 Jan 2017
  3. Primary completion21 Apr 2023
  4. Study completion25 Apr 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
87 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02567409
Sponsor's protocol ID
NCI-2015-01642
Other IDs
NCI-2015-01642, PHII-135, 9947, 9947, N01CM00038, UM1CA186690, UM1CA186717
Status last verified
Feb 2025
First submitted
2 Oct 2015
Last updated
3 Mar 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Pal SK, Frankel PH, Mortazavi A, Milowsky M, Vaishampayan U, Parikh M, Lyou Y, Weng P, Parikh R, Teply B, Dreicer R, Emamekhoo H, Michaelson D, Hoimes C, Zhang T, Srinivas S, Kim WY, Cui Y, Newman E, Lara PN Jr. Effect of Cisplatin and Gemcitabine With or Without Berzosertib in Patients With Advanced Urothelial Carcinoma: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2021 Oct 1;7(10):1536-1543. doi: 10.1001/jamaoncol.2021.3441.

    PubMed 34436521

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Berzosertib, Cisplatin and Gemcitabine Hydrochloride in people with Metastatic Bladder Urothelial Carcinoma and Metastatic Renal Pelvis and Ureter Urothelial Carcinoma, run by National Cancer Institute (NCI) at 39 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 39 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) (time frame: Day of randomization, until progression, or death, assessed up to 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02567409, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2025.

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