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

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ClinicalTrials.gov Identifier: NCT04887831
Recruitment Status : Recruiting
First Posted : May 14, 2021
Last Update Posted : December 6, 2021
Sponsor:
Information provided by (Responsible Party):
G1 Therapeutics, Inc.

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.

Condition or disease Intervention/treatment Phase
Urothelial Carcinoma Bladder Cancer Myelosuppression Adult Chemotherapy-induced Neutropenia Metastatic Bladder Cancer Drug: Trilaciclib Drug: Gemcitabine Drug: Cisplatin Drug: Carboplatin Drug: Avelumab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
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
Official Title: 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)
Actual Study Start Date : June 4, 2021
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : May 2024


Arm Intervention/treatment
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)
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

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)
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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04887831


Contacts
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Contact: G1 Therapeutics, Inc. Clinical Contact 919-213-9835 clinicalinfo@g1therapeutics.com

Locations
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Sponsors and Collaborators
G1 Therapeutics, Inc.
Investigators
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Study Director: Clinical Contact G1 Therapeutics, Inc.
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Responsible Party: G1 Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04887831    
Other Study ID Numbers: G1T28-209
First Posted: May 14, 2021    Key Record Dates
Last Update Posted: December 6, 2021
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by G1 Therapeutics, Inc.:
Trilaciclib dihydrochloride/Cosela
Metastatic Urothelial Carcinoma
Cyclin-dependent kinase 4/6 inhibitor
Immuno-oncology
Solid tumor
Chemotherapy-induced myelosuppression
Myeloprotective
Additional relevant MeSH terms:
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Carcinoma
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Neutropenia
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Agranulocytosis
Leukopenia
Leukocyte Disorders
Hematologic Diseases
Gemcitabine
Carboplatin
Avelumab
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological