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Metastatic Urothelial CancerPhase 1NCT01963052

ASG-15ME is a Study of Escalating Doses of AGS15E Given as Monotherapy in Subjects With Metastatic Urothelial Cancer

A Phase 1 study testing AGS15E in people with Metastatic Urothelial Cancer, run by Astellas Pharma Global Development, Inc. at 11 sites in 2 countries.

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

The objectives of this study are to assess the safety, pharmacokinetics, immunogenicity and anti-tumor activity of AGS15E in subjects with metastatic urothelial cancer who failed at least one prior chemotherapy regimen for metastatic disease. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Urothelial Cancer
What is being tested?
AGS15E
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
93 participants
Where
11 sitesin 2 countries
Study dates
14 Nov 2013to 8 Jul 2019
Phase
Phase 1
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed Transitional Cell Carcinoma of the Urothelium (TCCU) (i.e., cancer of the bladder, renal pelvis, ureter, or urethra). Subjects with Urothelial Carcinoma with squamous differentiation or mixed cell types are eligible.
  • Part A: Subject must have failed at least one prior chemotherapy regimen for metastatic disease and/or is unfit for cisplatin-based chemotherapy.
  • Part B: Subject must not have received any prior lines of chemotherapy in the metastatic setting (prior treatment with immunotherapy is allowed).
  • Part C (CPI-Treated Expansion): Subject must have received prior treatment with a CPI in the metastatic setting
  • Subjects must have measureable disease according to RECIST (version 1.1).
  • Part A and C: Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
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  • Part B: Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
  • Life expectancy of ≥ 3 months
  • Adequate hematologic function
  • Parts A and C: Renal function, as follows: serum creatinine ≤ 2.0 mg/dL, or measured 24 hour creatinine clearance of ≥ 45 mL/min
  • Part B: Renal function, as follows: creatinine clearance estimate ≥ 15 mL/min and <60 mL/min by Cockcroft Gault equation adjusted for body weight
  • Adequate liver function

Who cannot join

  • Preexisting sensory neuropathy Grade ≥ 2 or motor neuropathy Grade ≥ 2
  • Uncontrolled central nervous system metastases
  • Use of any investigational drug within 14 days prior to the first dose of study drug
  • Any anticancer therapy, including: small molecules, immunotherapy, chemotherapy, monoclonal antibody therapy, radiotherapy or any other agents to treat cancer (anti-hormonal therapy given as adjuvant therapy for early-stage estrogen receptor (ER) positive breast cancer is not considered cancer therapy for the purpose of this protocol)
  • Subjects with Immunotherapy related adverse events requiring high doses of steroids (≥ 40 mg/day of prednisone) are not eligible
  • Any P-gp inducers/inhibitors or strong CYP3A inhibitors within 14 days prior to the first dose of study drug
Show all 29Show fewer
  • History of thromboembolic events and/or bleeding disorders ≤ 14 days (e.g., deep vein thrombosis (DVT) or pulmonary embolism (PE)) prior to the first dose of study drug
  • Active angina or Class III or IV Congestive Heart Failure (CHF) (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 12 months of study enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by outpatient medication
  • Known HIV or AIDS
  • Positive Hepatitis B surface antigen test
  • Positive Hepatitis C antibody test
  • Decompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathy
  • Known sensitivity to any of the ingredients of the investigational product AGS15E
  • Major surgery within 28 days prior to first dose of study drug
  • History of a primary invasive malignancy not listed in the inclusion criteria, which has not been in remission for at least 3 years. The following are exempt from the 3 year limit:
  • Non-melanoma skin cancer;
  • adenocarcinoma of the prostate that has been surgically treated with a post-treatment PSA that is undetectable;
  • cervical carcinoma in situ on biopsy or squamous intraepithelial lesion on Pap smear; and
  • definitively treated, stage I/II ER+ breast cancer
  • Active infection requiring treatment ≤ 7 days before first dose of study drug
  • History of uncontrolled diabetes mellitus or diabetic neuropathy
  • Condition or situation which may put the subject at significant risk, may confound the study results, or may interfere significantly with subject's participation in the study
  • Has ocular conditions such as:
  • Active infection or corneal ulcer (e.g., keratitis)
  • Monocularity
  • History of corneal transplantation
  • Contact lens dependent (if using contact lens, must be able to switch to glasses during the entire study duration)
  • Uncontrolled glaucoma (topical medications allowed)
  • Uncontrolled or evolving retinopathy, wet macular degeneration, uveitis, papilledema, or optic disc disorder

Trial locations and contacts

11 sites in 2 countries.

11 sites in 2 countries

United States8 sites

  • Site US00006

    Birmingham, Alabama, 35294

  • Site US00009

    Buffalo, New York, 14263

  • Site US00001

    Detroit, Michigan, 48201

  • Site US00010

    Nashville, Tennessee, 37212

  • Site US00002

    New Haven, Connecticut, 06510

  • Site US00011

    Pittsburgh, Pennsylvania, 15232

  • Site US00008

    Seattle, Washington, 98109

  • Site US00003

    St Louis, Missouri, 63110

Other trials in United States

Canada3 sites

  • Site CA00007

    Hamilton, Ontario, L8V 5C2

  • Site CA00005

    Toronto, Ontario, M4N 3M5

  • Site CA00004

    Vancouver, British Columbia, V5Z 1H5

Other trials in Canada

About this study

Official title: A Phase 1 Study of the Safety and Pharmacokinetics of Escalating Doses of AGS15E Given as Monotherapy in Subjects With Metastatic Urothelial Cancer

The objectives of this study are to assess the safety, pharmacokinetics, immunogenicity and anti-tumor activity of AGS15E in subjects with metastatic urothelial cancer who failed at least one prior chemotherapy regimen for metastatic disease.

Read the detailed description

All subjects will receive a single intravenous infusion of AGS15E once weekly for 3 weeks of every 4 weeks. A cycle is 4 weeks. Subjects will continue treatment until disease progression, intolerability of AGS15E, investigator decision, or consent withdrawal.

In subjects who discontinue therapy without documented disease progression and who still consent to study procedures, every effort should be made to continue monitoring their disease status by radiographic imaging until progression is documented, or new anticancer therapy, or death. All subjects will continue to be followed for survival until withdrawal of consent or study closure.

If assessed as complete response (CR) or partial response (PR) per local review a confirmatory scan will be performed no less than 4 weeks from previous scan and preferably at week 5. Tumor imaging should also be performed whenever disease progression is suspected.

Images will be sent to a central third party imaging vendor for an independent assessment per RECIST version 1.1. Although the imaging studies will be reviewed by a central third party imaging vendor in a retrospective fashion, all clinical decisions will be based on the interpretation of the investigator at the site treating the subject.

Post-Treatment Follow-up Progression Free Survival:

Subjects who discontinued study treatment for reasons other than radiographic disease progression will continue for a maximum of up to 12 months following the last dose of study drug until radiologically confirmed progression, initiation of a new anticancer therapy, death, loss to follow-up or withdraw consent for further follow-up, whichever of these events occurs first. The purpose of the post-treatment follow-up is to ascertain the duration of progression-free survival for all subjects enrolled in the study.

Being tested
AGS15E
Keywords
Metastatic Urothelial Cancer, AGS15E, AGS15E-13-1, ASG-15ME, Pharmacokinetics of AGS15E

What participants receive

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

  • AGS15EDrug

    intravenous (IV) infusion

Study groups in NCT01963052
Study groupRoleWhat they receive
Part A: AGS-15E Dose Escalation (Dose Levels 1-6)ExperimentalSubjects will receive a single 30 minute intravenous (IV) infusion of AGS15E once weekly for 3 weeks of every 4 weeks (Days 1, 8, and 15). A cycle is 4 weeks. Additional subjects may be enrolled for expansion of these dose levels to further evaluate the safety and efficacy, as recommended by a data review team (DRT).
Receives: Drug: AGS15E
Part B: AGS-15E Cisplatin Therapy -ineligible ExpansionExperimentalUrothelial subjects who have not received any prior lines of therapy an who are unfit for Cisplatin therapy (Cis-ineligible) will receive a single 30 minute intravenous (IV) infusion of AGS15E once weekly for 3 weeks of every 4 weeks (Days 1, 8, and 15). A cycle is 4 weeks. Subjects will initially be dosed one dose level below the preliminary recommended phase 2 dose (RP2D).
Receives: Drug: AGS15E
Part C: AGS15E Immune Checkpoint Inhibitor Treated ExpansionExperimentalSubjects previously treated with immune checkpoint inhibitors (CPI) in the metastatic setting will receive a single 30 minute intravenous (IV) infusion of AGS15E once weekly for 3 weeks of every 4 weeks (Days 1, 8, and 15). A cycle is 4 weeks. Subjects will be dosed at the RP2D.
Receives: Drug: AGS15E
Part A: AGS15E Dose ExpansionExperimentalSubjects will receive a single 30 minute intravenous (IV) infusion of AGS15E once weekly for 3 weeks of every 4 weeks (Days 1, 8, and 15). A cycle is 4 weeks.
Receives: Drug: AGS15E

What is being measured

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

  1. Incidence of adverse events

    Measured: up to 36 months

  2. Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Concentration at the end of infusion (CEOI)

    Measured: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months

  3. Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Maximum observed concentration (Cmax)

    Measured: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months

  4. Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Trough concentration (Ctrough)

    Measured: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months

  5. Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Time to maximum concentration (Tmax)

    Measured: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months

  6. Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Partial area under the serum concentration-time curve after first dose and as appropriate (AUC0-7)

    Measured: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months

  7. Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Terminal or apparent terminal half-life (t1/2)

    Measured: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months

  8. Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Systemic clearance (CL)

    Measured: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months

  9. Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Volume of distribution at steady state (Vss)

    Measured: Days 1-4, 8, 15-18 and 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycles 2 and 3, and Day 1 of subsequent cycles up to an average of 6 months

Secondary outcomes (6)

  1. Incidence of Anti-Drug Antibody (ADA)

    Measured: Up to 26 months

  2. Tumor response

    Incidence of tumor response defined as either a complete response (CR) or partial response (PR) per RECIST criteria (version 1.1) that should be confirmed ≥ 28 days later

    Measured: Up to 26 months

  3. Objective response rate

    Defined as the percentage of subjects who experience a best response of either CR or PR in that cohort. CR and PR should be confirmed ≥ 28 days later

    Measured: Up to 26 months

  4. Disease control rate

    Defined as the percentage of subjects who experience a best response of CR, PR or stable disease (SD)

    Measured: Up to 26 months

  5. Progression free survival

    Time from the date of first infusion to the earliest date of documented disease progression per radiological evidence or death from any cause

    Measured: Up to 36 months

  6. Duration of response

    Time from the date of the first response CR or PR to the earliest date of disease progression or death from any cause

    Measured: 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 posted16 Oct 2013 (estimated)
  2. Study start14 Nov 2013
  3. Primary completion8 Jul 2019
  4. Study completion8 Jul 2019

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
93 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01963052
Sponsor's protocol ID
AGS15E-13-1
Status last verified
Oct 2024
First submitted
7 Oct 2013
Last updated
1 Nov 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Publications

  • Petrylak DP, Eigl BJ, George S, Heath EI, Hotte SJ, Chism DD, Nabell LM, Picus J, Cheng SY, Appleman LJ, Sonpavde GP, Morgans AK, Pourhosseini P, Wu R, Standley L, Croitoru R, Yu EY. Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of AGS15E Monotherapy in Patients with Metastatic Urothelial Carcinoma. Clin Cancer Res. 2024 Jan 5;30(1):63-73. doi: 10.1158/1078-0432.CCR-22-3627.

    PubMed 37861407

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AGS15E in people with Metastatic Urothelial Cancer, run by Astellas Pharma Global Development, Inc. at 11 sites in 2 countries.

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 12 inclusion and 29 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 1 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States, Canada. 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 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.

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?

Incidence of adverse events (time frame: up to 36 months). The study lists 9 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 NCT01963052, 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 1 Nov 2024.

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