AzTrials
AzTrials

Metastatic Urothelial CarcinomaPhase 1/2NCT02420847

Ixazomib Citrate With Gemcitabine Hydrochloride and Doxorubicin Hydrochloride in Treating Patients With Urothelial Cancer That is Metastatic or Cannot Be Removed by Surgery

A Phase 1/2 study testing Doxorubicin Hydrochloride, Gemcitabine Hydrochloride and Ixazomib Citrate in people with Metastatic Urothelial Carcinoma and Transitional Cell Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This phase I/II trial studies the side effects and best dose of ixazomib citrate, gemcitabine hydrochloride, and doxorubicin hydrochloride when given together in treating patients with urothelial cancer that has spread to other places in the body (metastatic) or cannot be removed by surgery. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Doxorubicin Hydrochloride, Gemcitabine Hydrochloride and Ixazomib Citrate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
57 participants
Where
1 siteUnited States
Study dates
3 Jul 2015to 31 Dec 2025
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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

  • All patients must have histologic demonstration of metastatic or locally unresectable transitional cell carcinoma of the urothelium; variant histology is allowed as long as there is an urothelial component present; the principal investigator (PI), will serve as the final arbiter of eligibility
  • All patients must have measurable or evaluable disease; in general, liver and lung lesions should be at least 1 cm, and patients with node-only disease should have lesions of >= 1.5 cm in greatest dimension; patients with disease confined to bone may be eligible if a measurable lytic defect is present or a serum marker is elevated (> 4 x upper limit of normal [ULN]); the principal investigator is the final arbiter in questions related to measurability; patients with a three-dimensional mass or pelvic sidewall fixation on bladder examination under anesthesia are considered to have measurable disease
  • Patients must have had at least one prior therapy to be eligible for either phase I or II, unless they are either not candidates for or refuse cisplatin-based therapy
  • Phase I: patients are eligible with any number of prior regimens regardless of what those regimens contained (i.e. prior bortezomib or combination gemcitabine and adriamycin is acceptable)
  • Phase II: patients are eligible if their previous chemotherapy regimen did not contain bortezomib, carfilzomib, or other known proteasome inhibitor or a combination of gemcitabine >= 800 mg/m^2 plus adriamycin >= 30 mg/m^2; patients who receive sequential or alternating therapy as part of front-line treatment will be counted as having one prior regimen; patients who have failed prior neoadjuvant chemotherapy will be eligible for this trial
  • If prior history of ischemic heart disease or exposure to 200 mg/m^2 of doxorubicin, patients must have a measured ejection fraction (either by multigated acquisition scan [MUGA], echocardiogram [ECHO], stress test, or ventriculography) of at least 45%
Show all 17Show fewer
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) levels =< 3 x the upper limit of normal
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2; patients with a PS of 3 are eligible if the performance status is due to their malignancy, and not a co-morbid medical condition (example [ex]: perineal pain impacting their ability to sit or ambulate, etc.)
  • Patients who:
  • Are postmenopausal for at least 1 year before the screening visit, OR
  • Are surgically sterile, OR
  • If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR
  • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
  • Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following:
  • Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
  • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
  • Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care

Who cannot join

  • Platelet count of < 100 x 10^9/L; platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment
  • An absolute neutrophil count of < 1.0 x 10^9/L
  • A calculated creatinine clearance of < 30 mL/min using Cockcroft Gault or measured by 24 hour urine
  • Patient has >= grade 3 peripheral neuropathy, or grade 2 with pain on clinical examination during the screening period
  • Total bilirubin >= 1.5 x the upper limit of the normal range (ULN)
  • Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
Show all 25Show fewer
  • Female subject is pregnant or breast-feeding
  • Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test (unless there is reasonable certainty that beta-hCG is coming from the tumor); pregnancy testing is not required for post-menopausal or surgically sterilized women
  • Participation in other clinical trials with investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial
  • Patients with significant atherosclerotic disease, as defined by:
  • Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • Symptomatic congestive heart failure
  • Claudication limiting activity and
  • History of cerebrovascular events within the last year (including transient ischemic attack [TIA])
  • Unstable angina
  • Patients with known active brain metastases; (subjects with previously treated brain metastases are eligible provided they are stable [defined as without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment] and neurologic symptoms have returned to baseline)
  • Radiotherapy within 28 days before enrollment; if the involved field is small, 14 days will be considered a sufficient interval between treatment and administration of the therapy
  • Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease; patients with pathologically confirmed completely resected prostate cancer no higher than stage pT2a and no biochemical relapse, or pT2c tumors involving less than 5% of the prostate and no biochemical relapse, nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
  • Systemic treatment, within 14 days before the first dose of ixazomib, with strong inhibitors of cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2) (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of cytochrome P450, family 3, subfamily A (CYP3A) (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort
  • Failure to have fully recovered (ie, =< grade 1 toxicity) from the reversible effects of prior chemotherapy
  • Major surgery within 14 days before enrollment; the PI will serve as the final arbiter as to what constitutes major surgery
  • Infection requiring current intravenous antibiotic therapy; the PI will serve as the final arbiter regarding eligibility
  • Ongoing or active systemic infection, known active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive
  • Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
  • Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing; patients who have had cystectomy with conduit, neobladder, or pouch using a portion of their terminal ileum are allowed if, the patient is stable without clinically significant metabolic disturbances OR stoma- and/or anastomosis-related complications OR post-surgical gut abnormalities that would compromise drug absorption

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase I Two-Dimensional Dose-Finding Study of Ixazomib in Combination With Gemcitabine and Doxorubicin, Followed by a Phase II Extension to Assess the Efficacy of This Combination in Metastatic, Surgically Unresectable Urothelial Cancer

This phase I/II trial studies the side effects and best dose of ixazomib citrate, gemcitabine hydrochloride, and doxorubicin hydrochloride when given together in treating patients with urothelial cancer that has spread to other places in the body (metastatic) or cannot be removed by surgery. Ixazomib citrate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as gemcitabine hydrochloride and doxorubicin 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 ixazomib citrate together with gemcitabine hydrochloride and doxorubicin hydrochloride may be a better treatment for urothelial cancer.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Find maximum tolerated doses (MTDs) for the combination therapy of ixazomib (ixazomib citrate) and gemcitabine (gemcitabine hydrochloride)/doxorubicin (doxorubicin hydrochloride) (i.e. dose pairs of ixazomib and gemcitabine/doxorubicin that have an acceptable target toxicity rate of 30%). (Phase I)

SECONDARY OBJECTIVES:

  1. Define the dose-limiting toxicities of the dose pairs found. II. Choose a dose pair for phase II expansion in patients with locally advanced or metastatic urothelial cancer.

III. Determine the objective response rate and median survival for patients treated on the phase II expansion.

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

Patients receive ixazomib citrate orally (PO), gemcitabine hydrochloride intravenously (IV) over 90 minutes, and doxorubicin hydrochloride IV over 15-30 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Medical subject headings
Carcinoma, Transitional Cell

What participants receive

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

  • Doxorubicin HydrochlorideDrug

    Also called 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin

    Given IV

  • Gemcitabine HydrochlorideDrug

    Also called dFdCyd, Difluorodeoxycytidine Hydrochloride, FF 10832, FF-10832

    Given IV

  • Ixazomib CitrateDrug

    Also called MLN-9708, MLN9708, Ninlaro

    Given PO

Study groups in NCT02420847
Study groupRoleWhat they receive
Treatment (ixazomib, gemcitabine, doxorubicin)ExperimentalPatients receive ixazomib citrate PO, gemcitabine hydrochloride IV over 90 minutes, and doxorubicin hydrochloride IV over 15-30 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Doxorubicin Hydrochloride; Drug: Gemcitabine Hydrochloride; Drug: Ixazomib Citrate

What is being measured

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

  1. Maximum tolerated doses (MTDs) for the combination therapy of ixazomib citrate and gemcitabine hydrochloride/doxorubicin hydrochloride, defined as dose pairs where the target dose limiting toxicity probability is 30% (phase I)

    Measured: At 14 days

Secondary outcomes (1)

  1. Objective response (phase II extension)

    Measured: Up to 2 years

Timeline

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

  1. First posted20 Apr 2015 (estimated)
  2. Study start3 Jul 2015
  3. Primary completion31 Dec 2025 (estimated)
  4. Study completion31 Dec 2025 (estimated)

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
57 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02420847
Sponsor's protocol ID
2014-0661
Other IDs
NCI-2015-00682, 2014-0661
Status last verified
Nov 2025
First submitted
15 Apr 2015
Last updated
10 Nov 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Doxorubicin Hydrochloride, Gemcitabine Hydrochloride and Ixazomib Citrate in people with Metastatic Urothelial Carcinoma and Transitional Cell Carcinoma, run by M.D. Anderson Cancer Center at 1 site 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 17 inclusion and 25 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: under way, not looking for participants, as of the sponsor's last update on 10 Nov 2025. 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 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 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?

This study is still under way. Results are not available in the source record yet.

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?

Maximum tolerated doses (MTDs) for the combination therapy of ixazomib citrate and gemcitabine hydrochloride/doxorubicin hydrochloride, defined as dose pairs where the target dose limiting toxicity probability is 30% (phase I) (time frame: At 14 days). 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 NCT02420847.

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 10 Nov 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in