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

Sponsor

G1 Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04887831

Collaborator

(none)

Enrollment

Locations

Arms

34.9

Anticipated Duration (Months)

1.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Random assignment (1:1) to one of two treatment armsRandom 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 :

Jun 4, 2021

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

May 1, 2024

Arms and Interventions

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 Names: 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 Names: Bavencio

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 Names:

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 Names:

Bavencio

Outcome Measures

Primary Outcome Measures

Progression-Free Survival [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

Anti-tumor Effects [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 [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 [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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
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)
Presence of central nervous system (CNS) metastases/leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.
QTcF interval > 480 msec. For patients with ventricular pacemakers, QTcF > 500 msec
Known hypersensitivity or allergy to avelumab, gemcitabine, cisplatin or carboplatin
Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any history of anaphylaxis, or uncontrolled asthma
Prior hematopoietic stem cell or bone marrow transplantation, or solid organ transplantation
Pregnant or lactating women
Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
Current use of immunosuppressive medication, EXCEPT for the following:
Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)
Systemic corticosteroids at physiological doses ≤10 mg/day of prednisone or equivalent
Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Valkyrie Clinical Trial	Los Angeles	California	United States	90067
2	Sarcoma Oncology Research Center	Santa Monica	California	United States	90403
3	The Oncology Institute of Hope and Innovation	Whittier	California	United States	90603
4	Rocky Mountain Cancer Centers	Littleton	Colorado	United States	80120
5	Florida Cancer Specialists - South	Fort Myers	Florida	United States	33901
6	Mid Florida Hematology and Oncology Center	Orange City	Florida	United States	32763
7	Woodlands Medical Specialists	Pensacola	Florida	United States	32503
8	Florida Cancer Specialists , North	Saint Petersburg	Florida	United States	33705
9	Saint Alphonsus Regional Medical Center	Boise	Idaho	United States	83706
10	Beacon Cancer Center PLLC	Coeur d'Alene	Idaho	United States	83814
11	XCancer / Northwest Oncology and Hematology	Rolling Meadows	Illinois	United States	60008
12	XCancer / Pontchartrain Cancer Center	Hammond	Louisiana	United States	70403
13	University of Maryland Greenebaum Comprehensive Cancer Center	Baltimore	Maryland	United States	21201
14	The Harry and Jeanette Weinberg Cancer Institute	Baltimore	Maryland	United States	21237
15	Maryland Oncology Hematology, P.A.	Silver Spring	Maryland	United States	20904
16	New York Oncology Hematology, P.C.	Albany	New York	United States	12206
17	Montefiore Medical Center	Bronx	New York	United States	10461
18	University of Buffalo	Williamsville	New York	United States	14203
19	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
20	Northwest Cancer Specialists, P.C.	Tigard	Oregon	United States	46241
21	University of Tennessee Medical Center	Knoxville	Tennessee	United States	37920
22	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37203
23	Texas Oncology-Austin Central	Austin	Texas	United States	78705
24	Valley Cancer Associates PA	Harlingen	Texas	United States	78550
25	Texas Oncology - Longview Cancer Center	Longview	Texas	United States	75601
26	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
27	Medical Oncology Associates, PS (dba Summit Cancer Centers)	Spokane	Washington	United States	99208
28	Hopitaux Universitaires de Strasbourg - Service Oncologie et Hématologie	Strasbourg	Bas-Rhin	France	67091
29	Hopitaux Universitaires de Strasbourg - Service Oncologie et Hématologie	Strasbourg	Bas-Rhin	France	67091
30	CHU de Nîmes - Institut de Cancérologie du Gard	Nîmes	Cedex 9	France	30029
31	Institut Bergonié - Oncologie Médicale et Pédiatrique	Bordeaux cedex	Gironde	France	33076
32	Centre Léon Bérard - Département d'oncologie médicale	Lyon		France	69373
33	Hôpital Européen Georges Pompidou - Service d'Oncologie Médicale	Paris		France	75015
34	Institut de Cancérologie de Lorraine	Vandœuvre-lès-Nancy		France	54519
35	High Technology Hospital MedCenter LTD	Batumi	Ajaria	Georgia	6010
36	National Center of Urology Named after Laur Managadze	Tbilisi		Georgia	0144
37	LTD "Aversi Clinic"	Tbilisi		Georgia	0160
38	LTD "Multiprofile Clinic Consilium Medulla"	Tbilisi		Georgia	186
39	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz - Rendeloint	Szolnok	Jász-Nagykun-Szolnok	Hungary	H-5000
40	Országos Onkológiai Intézet	Budapest		Hungary	1122
41	Semmelweis Egyetem, Urológiai Klinika	Budapest		Hungary	H-1082
42	Uzsoki Utcai Kórház	Budapest		Hungary	H-1145
43	Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona	Spain	08916
44	ALTHAIA, Xarxa Assistencial Universitiria de Manresa	Manresa	Barcelona	Spain	08243
45	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid	Spain	28222
46	Hospital Universitario Vall d´Hebron	Barcelona		Spain	08035
47	Hospital Clinic de Barcelona - Servicio de Oncología Médica	Barcelona		Spain	08036
48	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	08041
49	Hospital Universitari Parc Tauli	Barcelona		Spain	08208
50	H.U. V. de las Nieves	Granada		Spain	18014
51	Hospital Universitario Lucus Augusti	Lugo		Spain	27003
52	M.D. Anderson Center Madrid	Madrid		Spain	28033
53	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
54	Fundación Instituto Valenciano de Oncología	Valencia		Spain	46009
55	Hospital Politecnic Universitari La Fe	Valencia		Spain	46026