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

NCT03240016 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: UMCC 2017.077HUM00135166
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients That Respond to 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.

  24 months post treatment, an average of 7.5 months

Secondary Outcomes (5)

• Duration of Response

  24 months post treatment

• Progression Free Survival Time

  24 months post treatment

• Median Number of Patients Alive at 12 and 24 Months

  12 and 24 months post treatment

• Median Duration of Therapy

  from the start of therapy, up to 24 months

• Percentage of Patients That Completely Respond to Treatment

  24 months post treatment, an average of 7.5 months

Study Arms (1)

Pembrolizumab and Abraxane

EXPERIMENTAL

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

Drug: Pembrolizumab; Drug: Abraxane

Interventions

Pembrolizumab DRUG

200mg IV D1

Pembrolizumab and Abraxane

Abraxane DRUG

100mg/m\^2 D1 and D8

Pembrolizumab and Abraxane

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

• 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.

  PMID: 36317715 DERIVED

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

pembrolizumab; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: University of Michigan Rogel Cancer Center ClinicalTrials.gov Admin
• Organization: University of Michigan Rogel Cancer Center

ClinicalTrialsgov_CCAdmin@umich.edu

734-936-9499

Study Officials

• Ajjai Alva, M.D.

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2017
• First Posted: August 4, 2017
• Study Start: February 8, 2018
• Primary Completion: June 23, 2023
• Study Completion: June 23, 2023
• Last Updated: January 16, 2025
• Results First Posted: January 16, 2025

Record last verified: 2025-01

Locations

US (1)