Clinical Trials /

Abraxane With Anti-PD1/PDL1 in Patients With Advanced Urothelial Cancer

NCT03240016

Description:

This is a phase 2, single arm, two-stage study of abraxane with an anti-PD1/PDL1 (pembrolizumab) in cisplatin-ineligible patients with advanced urothelial cancer. Each cycle last 21-days. All subjects will receive pembrolizumab via IV on day 1, and abraxane via IV on Day 1 and Day 8 of each cycle. Subjects may continue to receive the study regimen until they experience disease progression or unacceptable toxicity.

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Abraxane With Anti-PD1/PDL1 in Patients With Advanced Urothelial Cancer
  • Official Title: ABLE: Phase II, Single Arm, Two-stage Study of Abraxane With Anti-PD1/PDL1 in Patients With Advanced Urothelial Cancer

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2017.077
  • SECONDARY ID: HUM00135166
  • NCT ID: NCT03240016

Conditions

  • Urothelial Carcinoma

Interventions

DrugSynonymsArms
PembrolizumabPembrolizumab and Abraxane
AbraxanePembrolizumab and Abraxane

Purpose

This is a phase 2, single arm, two-stage study of abraxane with an anti-PD1/PDL1 (pembrolizumab) in cisplatin-ineligible patients with advanced urothelial cancer. Each cycle last 21-days. All subjects will receive pembrolizumab via IV on day 1, and abraxane via IV on Day 1 and Day 8 of each cycle. Subjects may continue to receive the study regimen until they experience disease progression or unacceptable toxicity.

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab and AbraxaneExperimentalPembrolizumab 200mg IV D1 Abraxane 100mg/m^2 IV D1 and D8 21 Day Cycles
  • Pembrolizumab
  • Abraxane

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with recurrent unresectable locally advanced or metastatic urothelial
             carcinoma (aka transitional cell carcinoma).

          -  Patients may be either cisplatin-ineligible or platinum-refractory.

          -  Histological or cytologically proven urothelial carcinoma.

          -  Have measurable disease based on RECIST 1.1

          -  Has urothelial cancer that is not suitable for local therapy administered with
             curative intent if not already administered.

          -  Must have recovered (i.e., AE <= Grade 1 or stable) from AEs due to a previously
             administered agent.

          -  ECOG Performance Status of 0, 1 or 2. (Eastern Cooperative Oncology Group Performance
             Status: an attempt to quantify cancer patients' general well-being and activities of
             daily life. The score ranges from 0 to 5 where 0 is asymptomatic and 5 is death.)

          -  Prior neoadjuvant or adjuvant systemic therapy or local intravesical chemotherapy or
             immunotherapy is permitted.

          -  Adequate organ and marrow function

          -  Women of child-bearing potential must either commit to true abstinence or agree to
             use, and be able to comply with, effective contraception without interruption, 28 days
             prior to starting IP therapy, and while on study medication or for a longer period if
             required by local regulations following the last dose of IP; and have a negative serum
             pregnancy test result at screening

          -  Male subjects must practice true abstinence or agree to use a condom during sexual
             contact with a pregnant female or a female of childbearing potential while
             participating in the study, during dose interruptions and for 6 months following drug
             discontinuation, even if he has undergone a successful vasectomy.

          -  Patients must have < Grade 2 pre-existing peripheral neuropathy

          -  Be ≥18 years of age as of date of signing informed consent

          -  Voluntarily agree to participate by providing written informed consent/assent for the
             trial

        Exclusion Criteria:

          -  Prior exposure to immune-mediated therapy

          -  History of allogenic organ transplantation that requires ongoing use of
             immunosuppressive agents is NOT permitted

          -  Active or prior documented autoimmune or inflammatory disorders are NOT permitted

          -  Current or prior use of immunosuppressive medication(s) within 14 days before study
             treatment is NOT permitted.

          -  Brain metastases or spinal cord compression are NOT permitted unless they have been
             treated with the patient's condition being stable clinically and radiologically for 28
             calendar days and off steroids for at least 14 days prior to the start of study
             treatment.

          -  Active infection including tuberculosis, hepatitis B, hepatitis C, or human
             immunodeficiency virus (HIV) is NOT permitted.

          -  Receipt of live attenuated vaccine within 30 days prior to the first study treatment
             is NOT permitted.

          -  Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy or used an investigation device
             within 28 calendar days of the first dose of treatment.

          -  CTCAE Grade > 1 peripheral neuropathy is NOT permitted

          -  If subjects received major surgery they must have recovered adequately from the
             toxicity and/or complications from the intervention prior to starting trial therapy

          -  Has a known additional malignancy that is progressing or requires active treatment

          -  Has a history of severe hypersensitivity reaction to nab-paclitaxel or anti-PD1/PDL1

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial

          -  Pregnancies:

               1. Females: nab-paclitaxel can cause harm to an unborn child if given to a pregnant
                  woman. Females may not take part in this study if pregnant or breast-feeding for
                  6 months after last dose of study drug.

               2. Males: Male subjects should avoid fathering a child while receiving study
                  medication and for 6 months after the last dose of study medication. Males must
                  agree to complete abstinence from heterosexual contact or use a condom during
                  sexual contact with a female of child bearing potential while receiving study
                  medication and within 6 months after last dose of study medication.

               3. Subjects (both males and female) should practice effective contraception during
                  study and for 6 months after the last dose of study medication (Section 3.1.8 i,
                  ii).

          -  Patients with biliary obstruction or biliary stent are excluded.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of patients that respond to treatment
Time Frame:24 months post treatment
Safety Issue:
Description:The Overall Response Rate (ORR) will be the percentage of patients that achieve either complete response (CR) or partial response (PR). CR is defined as the disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions.

Secondary Outcome Measures

Measure:Duration of response
Time Frame:24 months post treatment
Safety Issue:
Description:The duration of response (DOR) is measured from the time that response (PR or CR) criteria are met until the first date that recurrent or progressive disease is objectively documented. CR is defined as the disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions.
Measure:Progression free survival time
Time Frame:24 months post treatment
Safety Issue:
Description:Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death. Progressive disease (PD) is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions.
Measure:Median number of patients alive at 12 and 24 months
Time Frame:12 and 24 months post treatment
Safety Issue:
Description:Overall survival will be documented as the median number of patients alive at 12 and 24 months.
Measure:Median duration of therapy
Time Frame:24 months post treatment
Safety Issue:
Description:
Measure:Percentage of patients that completely respond to treatment
Time Frame:24 months post treatment
Safety Issue:
Description:The percentage of patients that achieve complete response to treatment. Complete response is defined as the disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Michigan Rogel Cancer Center

Last Updated

June 2, 2020