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Trilaciclib, a CDK 4/6 Inhibitor, in Patients With Advanced/Metastatic Bladder Cancer Receiving Chemotherapy Then Avelumab (PRESERVE3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04887831
Recruitment Status : Active, not recruiting
First Posted : May 14, 2021
Last Update Posted : January 26, 2023
Sponsor:
Information provided by (Responsible Party):
G1 Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE May 5, 2021
First Posted Date  ICMJE May 14, 2021
Last Update Posted Date January 26, 2023
Actual Study Start Date  ICMJE June 4, 2021
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 13, 2021)
Progression-Free Survival [ Time Frame: From date of randomization until date of documented radiologic disease progression per RECIST v1.1 or death due to any cause, whichever comes first (on average 7 months) ]
To evaluate the effect of trilaciclib on progression-free survival (PFS) when administered with platinum-based chemotherapy followed by trilaciclib administered with avelumab maintenance therapy compared with platinum-based chemotherapy followed by avelumab maintenance therapy alone.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 13, 2021)
  • Anti-tumor Effects [ Time Frame: From date of randomization until date of documented radiologic disease progression per RECIST v1.1 or death due to any cause, whichever comes first (on average 7 months) ]
    To assess objective response rates as measured by RECIST 1.1
  • Anti-tumor Effects [ Time Frame: From date of randomization until date of death due to any cause (on average 25 months) ]
    To evaluate the effect of trilaciclib on overall survival (OS) when administered with platinum-based chemotherapy followed by trilaciclib administered with avelumab maintenance therapy compared with platinum-based chemotherapy followed by avelumab maintenance therapy alone.
  • Myeloprotective Effects [ Time Frame: Cycle 1 Day 1 (each cycle is 21 days) through treatment with platinum-based chemotherapy (up to 4 months) ]
    To assess the effects of trilaciclib on the neutrophil lineage as measured by the occurrence of severe neutropenia during platinum-based chemotherapy treatment
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trilaciclib, a CDK 4/6 Inhibitor, in Patients With Advanced/Metastatic Bladder Cancer Receiving Chemotherapy Then Avelumab
Official Title  ICMJE A Phase 2, Randomized, Open-Label Study of Trilaciclib Administered With First-Line Platinum-Based Chemotherapy and Avelumab Maintenance Therapy in Patients With Untreated, Locally Advanced or Metastatic Urothelial Carcinoma (PRESERVE 3)
Brief Summary This is a Phase 2, multicenter, randomized, open-label study evaluating the safety and efficacy of trilaciclib administered with platinum-based chemotherapy followed by trilaciclib administered with avelumab maintenance therapy compared with platinum-based chemotherapy followed by avelumab maintenance therapy in patients receiving first-line treatment for advanced/metastatic bladder cancer.
Detailed Description

Patients will be randomly assigned (1:1) to receive standard of care platinum-based chemotherapy (with or without the addition of trilaciclib) administered intravenously (IV) in 21-day cycles followed by standard of care avelumab maintenance therapy (with or without the addition of trilaciclib) administered IV in 14-day cycles.

Patients enrolled in the study will be eligible to receive 4-6 cycles of platinum-based chemotherapy, and patients without progressive disease (PD) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines (i.e., with an ongoing complete response [CR], partial response [PR], or stable disease) after platinum-based chemotherapy will be eligible to receive avelumab maintenance therapy until disease progression, unacceptable toxicity, withdrawal of consent, Investigator decision, or the end of the trial, whichever comes first.

Patients will be followed for survival approximately every 3 months after receiving the last dose of study medication.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Random assignment (1:1) to one of two treatment arms
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Urothelial Carcinoma
  • Bladder Cancer
  • Myelosuppression Adult
  • Chemotherapy-induced Neutropenia
  • Metastatic Bladder Cancer
Intervention  ICMJE
  • Drug: Trilaciclib
    Trilaciclib administered IV prior to chemotherapy and avelumab maintenance therapy on each day chemotherapy and avelumab maintenance therapy is administered.
    Other Names:
    • Cosela
    • G1T28
  • Drug: Gemcitabine
    Gemcitabine administered IV on Day 1 and Day 8 of each 21-day cycle
  • Drug: Cisplatin
    Cisplatin administered IV on Day 1 of each 21-day cycle
  • Drug: Carboplatin
    Carboplatin administered IV on Day 1 of each 21-day cycle
  • Drug: Avelumab
    Avelumab will be dosed on Day 1 of each 14-day maintenance cycle
    Other Name: Bavencio
Study Arms  ICMJE
  • Active Comparator: Platinum-based chemotherapy followed by avelumab maintenance therapy
    Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) or Carboplatin (AUC 4.5) followed by Avelumab (800 mg)
    Interventions:
    • Drug: Gemcitabine
    • Drug: Cisplatin
    • Drug: Carboplatin
    • Drug: Avelumab
  • Experimental: Trilaciclib plus platinum-based chemotherapy followed by avelumab maintenance therapy
    Trilaciclib (240 mg/m2) + Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) or Carboplatin (AUC 4.5) followed by Trilaciclib (240 mg/m2) + Avelumab (800 mg)
    Interventions:
    • Drug: Trilaciclib
    • Drug: Gemcitabine
    • Drug: Cisplatin
    • Drug: Carboplatin
    • Drug: Avelumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 25, 2022)
92
Original Estimated Enrollment  ICMJE
 (submitted: May 13, 2021)
90
Estimated Study Completion Date  ICMJE May 2024
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age ≥18 years
  2. Histologically documented, locally advanced (T4b, any N; or any T, N 2-3) or metastatic urothelial carcinoma (M1, Stage IV)
  3. Measurable disease as defined by RECIST v1.1
  4. No prior systemic therapy in the inoperable, locally advanced, or metastatic setting including chemotherapy, immune checkpoint inhibitor therapy, targeted therapy, or investigational agents
  5. Archival tumor tissue must be available or a fresh biopsy must be obtained, unless approved by the Medical Monitor
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  7. Adequate organ function as demonstrated by normal laboratory values

Exclusion Criteria:

  1. Prior treatment with IL-2, IFN-α, or an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or CD137 agonists, or cytotoxic T-lymphocyte associated protein 4 (CTLA-4) antibody (including ipilimumab), or any other therapeutic antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways in any setting
  2. Malignancies other than urothelial carcinoma within 3 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, or low-grade (Gleason ≤6) prostate cancer on surveillance without any plans for treatment intervention (e.g., surgery, radiation, or castration)
  3. Presence of central nervous system (CNS) metastases/leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.
  4. QTcF interval > 480 msec. For patients with ventricular pacemakers, QTcF > 500 msec
  5. Known hypersensitivity or allergy to avelumab, gemcitabine, cisplatin or carboplatin
  6. Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any history of anaphylaxis, or uncontrolled asthma
  7. Prior hematopoietic stem cell or bone marrow transplantation, or solid organ transplantation
  8. Pregnant or lactating women
  9. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
  10. Current use of immunosuppressive medication, EXCEPT for the following:

    1. Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)
    2. Systemic corticosteroids at physiological doses ≤10 mg/day of prednisone or equivalent
    3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Georgia,   Hungary,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04887831
Other Study ID Numbers  ICMJE G1T28-209
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party G1 Therapeutics, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE G1 Therapeutics, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Contact G1 Therapeutics, Inc.
PRS Account G1 Therapeutics, Inc.
Verification Date January 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP