Nab-paclitaxel Plus Gemcitabine as First-line Therapy for Cisplatin-ineligible or Cisplatin-incurable Advanced Urothelial Carcinoma

NCT02887248 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: SCRI GU 124
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this trial is to determine the benefit of the combination of nab-paclitaxel plus gemcitabine given for 6 cycles, followed by maintenance nab-paclitaxel alone, in patients with cisplatin-ineligible or cisplatin-incurable advanced urothelial carcinoma (UC).

Conditions

Urothelial Carcinoma; Bladder Cancer; Transitional Cell Carcinoma

Keywords

nab-paclitaxel; gemcitabine

Outcome Measures

Primary Outcomes (1)

• 6 Month Progression-free Survival (PFS6)

  The percentage of treated patients who are progression-free at 6 months after start of treatment, assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Progressive disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest (nadir) sum since the treatment started, or the appearance of one or more new lesions. Requires not only 20% increase, but absolute increase of a minimum of 5 mm over sum.

  up to 26 weeks

Secondary Outcomes (4)

• Overall Response Rate

  every 3 cycles (9 weeks) until treatment discontinuation, an expected average of 1 year.

• Clinical Benefit Rate

  every 3 cycles (9 weeks) until treatment discontinuation, an expected average of 1 year.

• Overall Survival

  every 9 weeks until disease progression or death on study, an expected average of 1 year. Patients with progressive disease will be followed every 3 months for the first year and every 6 months thereafter up to 5 years.

• The Number of Participants With Grade 3/4/5 Adverse Events (AEs) as a Measure of Safety.

  through study completion, an average of 1 year

Study Arms (1)

nab-paclitaxel+gemcitabine

EXPERIMENTAL

Induction Phase: nab-paclitaxel (125 mg/m²) and gemcitabine (1000 mg/m²) by IV infusion on Days 1 and 8 of each 21-day cycle. Responding or stable patients will be treated with a minimum of 3 cycles and up to 6 cycles before starting the single agent maintenance therapy. Maintenance Phase: Patients completing 3-6 cycles of induction therapy with an objective response (complete or partial response) or stable disease will continue treatment with single agent nab-paclitaxel (260 mg/m²) by IV infusion every 21 days) until disease progression, intolerable toxicity or patient decision to discontinue treatment.

Drug: nab-paclitaxel; Drug: Gemcitabine

Interventions

nab-paclitaxel DRUG

Induction: 125 mg/m² by intravenous (IV) infusion on Days 1 and 8 of each 21-day cycle for 3 to 6 cycles to be given with Gemcitabine. Maintenance: single agent nab-paclitaxel (260 mg/m²) by IV infusion every 21 days) until disease progression, intolerable toxicity or patient decision to discontinue treatment.

Also known as: Abraxane

nab-paclitaxel+gemcitabine

Gemcitabine DRUG

Induction: 1000 mg/m²) by IV infusion on Days 1 and 8 of each 21-day cycle for 3 to 6 cycles.

Also known as: Gemzar

nab-paclitaxel+gemcitabine

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of urothelial carcinoma (UC) that is either metastatic (any N+ M1) or locally advanced and unresectable (T4bN0). A component of urothelial (transitional cell) carcinoma is required.
• Two groups of patients are eligible:
• Poor candidates for cisplatin-based chemotherapy based on the presence of ≥ 1 the following:
• Glomerular filtration rate of 30-60 ml/min (Cockcroft-Gault formula)
• ECOG performance status score of 2
• Hearing loss (trouble communicating with hearing aids or hearing loss at ≤ 3 KHz)
• Grade ≥3 heart failure
• Age ≥80 years
• Other concurrent illness which may make the patient a poor candidate for receiving cisplatin.
• Note: Enrollment of patients with 2 or more of these criteria should occur only after careful consideration by the treating physician regarding the patient's ability to tolerate combination chemotherapy.
• Poor prognosis and defined as cisplatin-incurable due to the presence of metastasis to at least one visceral site (these patients are not required to have any of the cisplatin-ineligibility criteria).
• ECOG performance status score of 0, 1, or 2.
• Measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Patients with brain metastases are allowed if treatment was completed at least 4 weeks prior to study treatment, neurologic symptoms are minimal and stable during the preceding 4 weeks, and maintenance dexamethasone is not required.
• Adequate hematologic, liver and kidney function.

You may not qualify if:

• Previous systemic chemotherapy for UC with the exception of perioperative (neoadjuvant or adjuvant) treatment or treatment with concurrent chemoradiation for locally advanced disease. All of these treatments must have been completed more than 1 year previously.
• Presence of small-cell or sarcomatoid component in tumor histology.
• Women who are pregnant or breast-feeding.
• Major surgical procedures ≤28 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting required following port-a-cath placement.
• Cardiac diseases currently or within the last 6 months:
• Inadequately controlled hypertension.
• Currently receiving treatment with therapeutic doses of warfarin sodium. (A maximum daily dose of 1 mg will be permitted for port line patency. Low molecular weight heparin is allowed.)
• Serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
• Known diagnosis of human immunodeficiency virus, hepatitis B or hepatitis C (screening for these diseases is not required.).
• Presence of other active cancers, or history of treatment for invasive cancer ≤5 years previously. Patients with Stage I cancer who have received definitive local treatment and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Celgene: collaborator

Study Sites (5)

Florida Cancer Specialists - South

Fort Myers, Florida, 33916, United States

Location

Florida Cancer Specialists-North

St. Petersburg, Florida, 33705, United States

Location

Florida Cancer Specialists-East

West Palm Beach, Florida, 33401, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Center for Cancer and Blood Disorders

Fort Worth, Texas, 76104, United States

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Urinary Bladder Neoplasms

Interventions

130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Gemcitabine

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Sarah Cannon
• Organization: Sarah Cannon Development Innovations, LLC

CANN.InnovationsMedical@sarahcannon.com

844-710-6157

Study Officials

• John Hainsworth, MD

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: August 29, 2016
• First Posted: September 2, 2016
• Study Start: January 12, 2017
• Primary Completion: May 1, 2020
• Study Completion: May 1, 2020
• Last Updated: December 5, 2023
• Results First Posted: January 13, 2022

Record last verified: 2021-12

Locations

US (5)