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

• ClinicalTrials.gov Identifier: NCT03240016
• Recruitment Status: Completed
• First Posted: August 4, 2017
• Last Update Posted: August 31, 2023
• Sponsor: University of Michigan Rogel Cancer Center
• Information provided by (Responsible Party): University of Michigan Rogel Cancer Center

Tracking Information

• First Submitted Date: July 27, 2017
• First Posted Date: August 4, 2017
• Last Update Posted Date: August 31, 2023
• Actual Study Start Date: February 8, 2018
• Actual Primary Completion Date: June 23, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 3, 2017)

Percentage of patients that respond to treatment [ Time Frame: 24 months post treatment ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 2, 2020)

• Duration of response [ Time Frame: 24 months post treatment ]
  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.
• Progression free survival time [ Time Frame: 24 months post treatment ]
  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.
• Median number of patients alive at 12 and 24 months [ Time Frame: 12 and 24 months post treatment ]
  Overall survival will be documented as the median number of patients alive at 12 and 24 months.
• Median duration of therapy [ Time Frame: 24 months post treatment ]
• Percentage of patients that completely respond to treatment [ Time Frame: 24 months post treatment ]
  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.

Original Secondary Outcome Measures (submitted: August 3, 2017)

• Duration of response [ Time Frame: 24 months post treatment ]
  The duration of response (DOR) is measured from the time that response (PR or CR) is 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.
• Progression free survival time [ Time Frame: 24 months post treatment ]
  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.
• Median number of patients alive at 12 and 24 months [ Time Frame: 12 and 24 months post treatment ]
  Overall survival will be documented as the median number of patients alive at 12 and 24 months.
• Median duration of therapy [ Time Frame: 24 months post treatment ]
• Percentage of patients that completely respond to treatment [ Time Frame: 24 months post treatment ]
  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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Urothelial Carcinoma

Intervention

• Drug: Pembrolizumab
  200mg IV D1
• Drug: Abraxane
  100mg/m^2 D1 and D8

Study Arms

Experimental: Pembrolizumab and Abraxane

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

Interventions:

• Drug: Pembrolizumab
• Drug: Abraxane

• Publications *: Tsung I, Green E, Palmbos P, Sloan Z, Reichert ZR, Vaishampayan U, Smith DC, Caram MEV, Yentz S, Daignault-Newton S, Hurley L, Nguyen CB, Kraft S, Alva A. A Phase 2 Trial of Nab-paclitaxel in Combination With Anti-PD1 Therapy in Advanced Urothelial Cancer. J Urol. 2023 Jan;209(1):121-130. doi: 10.1097/JU.0000000000002969. Epub 2022 Nov 1.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 3, 2017): 36
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: June 23, 2023
• Actual Primary Completion Date: June 23, 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03240016
• Other Study ID Numbers: UMCC 2017.077; HUM00135166 ( Other Identifier: University of Michigan )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

• IPD Sharing Statement: Not Provided
• Current Responsible Party: University of Michigan Rogel Cancer Center
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Michigan Rogel Cancer Center
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Ajjai Alva, M.D.; University of Michigan Rogel Cancer Center

• PRS Account: University of Michigan Rogel Cancer Center
• Verification Date: August 2023