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Bladder CancerPhase 1/2NCT01090466

Gemcitabine Hydrochloride, Cisplatin, and Temsirolimus as First-Line Therapy in Treating Patients With Locally Advanced and/or Metastatic Transitional Cell Cancer of the Urothelium

A Phase 1/2 study testing cisplatin, gemcitabine hydrochloride and temsirolimus in people with Bladder Cancer and Transitional Cell Cancer of the Renal Pelvis and Ureter, run by Cardiff University at 1 site in United Kingdom.

Completed

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

Official record
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Trial summary

RATIONALE: Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 16 to 120 years
What is being tested?
cisplatin, gemcitabine hydrochloride and temsirolimus
How many people
15 participants
Where
1 siteUnited Kingdom
Study dates
Feb 2008to 16 Mar 2016
Phase
Phase 1/2
Are there results?
None posted in the registry

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 16 to 120 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

DISEASE CHARACTERISTICS:

  • Histologically confirmed transitional cell carcinoma of the urothelium
  • Pure or mixed histology
  • Upper or lower urinary tract
  • Radiologically evaluable* locally advanced and/or metastatic disease not amenable to curative treatment with surgery or radiotherapy, meeting any 1 of the following criteria:
  • T4b, any N, any M
  • Any T, N2-3, any M
  • Any T, any N, M1
  • NOTE: *Patients enrolled in the phase II portion of the trial must have radiologically measurable disease.
  • No transitional cell cancer for which subsequent radical treatment is being considered with a view to possibly cure the disease
  • No history of CNS metastases

PATIENT CHARACTERISTICS:

  • WHO performance status 0-2
  • Life expectancy ≥ 3 months
  • Absolute neutrophil count ≥ 1.5 x 10^9/L
  • Platelet count ≥ 100 x 10^9/L
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT and ALP ≤ 2.5 times ULN
  • PT or INR ≤ 1.5
  • GFR ≥ 60 mL/min (uncorrected for surface area and measured by isotopic means)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Fit to receive cisplatin-containing combination chemotherapy
  • No previous malignancy other than nonmelanoma skin cancer, carcinoma in situ of the cervix, or incidental localized prostate cancer
  • No known HIV positivity or chronic hepatitis B or C infection
  • No symptomatic coronary artery disease, myocardial infarction within the past 6 months, congestive cardiac failure (NYHA class III or IV disease), or uncontrolled or symptomatic cardiac arrhythmia
  • No clinically significant bacterial or fungal infection

PRIOR CONCURRENT THERAPY:

  • At least 1 month since prior radiotherapy or radiotherapy involving more than 30% of total bone marrow volume
  • At least 1 month since prior investigational drug
  • No prior systemic therapy for locally advanced or metastatic disease
  • Patients who have received prior neoadjuvant or adjuvant chemotherapy for urothelial cancer (up to 4 courses), completed at least 6 months prior to first documented disease progression are eligible
  • No concurrent anticoagulant therapy with warfarin or unfractionated heparin
  • Patients requiring anticoagulation may be entered on study after successful conversion to low molecular weight heparin
  • No concurrent medications which have known adverse interactions with the treatment used on this trial (e.g., CYP3A4 inhibitors or inducers in phase I of this trial)
  • No prior or concurrent live vaccines (e.g., measles, mumps, rubella, oral polio, Bacille Calmette-Guérin [BCG], yellow fever, varicella, and TY21a typhoid vaccines)
  • No concurrent grapefruit juice

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • Leeds Cancer Centre at St. James's University Hospital

    Leeds, England, LS9 7TF

Other trials in United Kingdom

About this study

Official title: A Phase I/II Single-Arm Trial to Evaluate the Combination of Cisplatin and Gemcitabine With the mTOR Inhibitor Temsirolimus for First-Line Treatment of Patients With Advanced Transitional Cell Carcinoma of the Urothelium

RATIONALE: Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine hydrochloride and cisplatin together with temsirolimus may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of temsirolimus given together with gemcitabine hydrochloride and cisplatin as first-line therapy in treating patients with locally advanced and/or metastatic transitional cell cancer of the urothelium.

Read the detailed description

OBJECTIVES:

Primary

  • To determine a safety profile of temsirolimus in combination with cisplatin and gemcitabine hydrochloride, including dose-limiting toxicities (DLTs) and maximum-tolerated dose (MTD) in patients with locally advanced and/or metastatic transitional cell carcinoma of the urothelium. (phase I)
  • To determine the recommended dose for the Phase II stage of the trial and subsequent studies. (phase I)
  • To assess progression-free survival (PFS) at six months from date of enrollment. (phase II)

Secondary

  • To determine the pharmacokinetic profile of temsirolimus in combination with cisplatin and gemcitabine hydrochloride. (phase I)
  • To determine tolerability (side-effects) and feasibility (number of participants requiring dose delays or reduction and/or treatment withdrawal). (phase II)
  • To determine objective response rate as assessed by RECIST. (phase II)
  • To assess PFS of these patients. (phase II)
  • To assess overall survival of these patients. (phase II)
  • To determine toxicity during and after treatment in these patients. (phase II)

OUTLINE: This is a multicenter, phase I dose-escalation study of temsirolimus followed by a phase II study.

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, cisplatin IV over 3-4 hours on day 1, and temsirolimus IV over 30 minutes on days 1 or 2, 8 or 9, and 15. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Blood specimens may be collected periodically for pharmacokinetic studies.

After completion of study treatment, patients are followed at 6 months and 1 year.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

Keywords
transitional cell carcinoma of the bladder, recurrent bladder cancer, recurrent urethral cancer, recurrent transitional cell cancer of the renal pelvis and ureter, stage IV bladder cancer, metastatic transitional cell cancer of the renal pelvis and ureter, regional transitional cell cancer of the renal pelvis and ureter, distal urethral cancer, proximal urethral cancer, urethral cancer associated with invasive bladder cancer, stage IV urethral cancer
Medical subject headings
Urinary Bladder Neoplasms, Urethral Neoplasms

What participants receive

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

What is being measured

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

  1. Safety (recommended phase II dose and dose-limiting toxicities) (phase I)

  2. Progression-free survival at 6 months (phase I)

Secondary outcomes (6)

  1. Pharmacokinetics (phase I)

  2. Safety, including tolerability and feasibility (phase II)

  3. Overall survival (phase II)

  4. Progression-free survival (time-to-event) (phase II)

  5. Objective (radiological) response rate according to RECIST criteria (phase II)

  6. Toxicity during and after treatment according to NCI CTCAE v 3.0 (phase II)

Timeline

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

  1. First posted22 Mar 2010 (estimated)
  2. Study startFeb 2008
  3. Primary completionJan 2010
  4. Study completion16 Mar 2016

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01090466
Sponsor's protocol ID
CDR0000667766
Other IDs
WCTU-TOTEM, ISRCTN31546330, EUDRACT-2007-007615-82, EU-21014, WCTU-SPON-417-07, CRUK-08/015
Status last verified
Feb 2018
First submitted
18 Mar 2010
Last updated
6 Feb 2018
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing cisplatin, gemcitabine hydrochloride and temsirolimus in people with Bladder Cancer and Transitional Cell Cancer of the Renal Pelvis and Ureter, run by Cardiff University at 1 site in United Kingdom.

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

Who may be eligible to take part?

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 6 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Safety (recommended phase II dose and dose-limiting toxicities) (phase I). The study lists 2 primary outcomes in all. 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 NCT01090466.

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 6 Feb 2018.

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