Trial Title:
A Study of Avutometinib (VS-6766) + Defactinib (VS-6063) in Recurrent Low-Grade Serous Ovarian Cancer
NCT ID:
NCT06072781
Condition:
Low Grade Serous Ovarian Cancer
Conditions: Official terms:
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Paclitaxel
Doxorubicin
Liposomal doxorubicin
Letrozole
Anastrozole
Conditions: Keywords:
Low Grade Serous Ovarian Cancer
KRAS
KRAS wt
KRAS mt
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Crossover Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
avutometinib
Description:
Avutometinib: administered orally
Arm group label:
avutometinib + defactinib
Other name:
avutometinib (VS-6766)
Intervention type:
Drug
Intervention name:
Defactinib
Description:
Defactinib: administered orally
Arm group label:
avutometinib + defactinib
Other name:
defactinib (VS-6063)
Intervention type:
Drug
Intervention name:
Pegylated liposomal doxorubicin
Description:
administered intravenously
Arm group label:
Investigator Choice of Treatment (ICT)
Other name:
Caelyx, Doxil, Lipodox
Intervention type:
Drug
Intervention name:
Paclitaxel
Description:
administered intravenously
Arm group label:
Investigator Choice of Treatment (ICT)
Other name:
Nov-Onxol, Onxol, Navaplus, Taxol
Intervention type:
Drug
Intervention name:
Letrozole
Description:
administered orally
Arm group label:
Investigator Choice of Treatment (ICT)
Other name:
Femara
Intervention type:
Drug
Intervention name:
Anastrozole
Description:
administered orally
Arm group label:
Investigator Choice of Treatment (ICT)
Other name:
Arimidex
Summary:
This study will assess the safety and efficacy of avutometinib (VS-6766) in combination
with defactinib versus Investigator's choice of treatments (ICT) in subjects with
recurrent LGSOC who have progressed on a prior platinum-based therapy.
Detailed description:
This international, randomized, open-label, Phase 3 study will compare the
investigational combination of avutometinib plus defactinib versus Investigator's Choice
of Treatments (ICT) in patients with recurrent LGSOC who have progressed on a prior
platinum-based therapy. Avutometinib and defactinib are both types of drugs called kinase
inhibitors. Kinase inhibitors block cancer cell growth. The study will compare the
progression-free survival (PFS) of the combination of avutometinib plus defactinib versus
ICT. The study will also evaluate the effect of the combination on safety, overall
survival, other efficacy endpoints, and health-related quality of life and disease
related symptoms. The study is being conducted by gynecological cancer specialists.
Patients who are eligible and agree to participate in this study will be treated with
either a combination of avutometinib with defactinib, or with one of four standard of
care NCCN and ESMO treatment recommendations for recurrent LGSOC, and then with
subsequent follow up appointments. Patients who originally received one of the standards
of care treatments who are determined to have progressive disease may be eligible to
crossover to receive the investigational combination avutometinib plus
defactinib.Avutometinib and defactinib are investigational drugs that have not been
approved by the U.S. Food and Drug Administration (FDA)
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Patients may be eligible for inclusion in the study if they meet the following criteria:
1. Histologically proven LGSOC (ovarian, fallopian, peritoneal)
2. Documented mutational status of KRAS by a validated tumor-tissue based diagnostic
test.
3. Suitable for treatment with at least one of the Investigator's Choice of
Treatments:pegylated liposomal doxorubicin, paclitaxel, letrozole, anastrozole.
4. Progression or recurrence of LGSOC after at least one prior systemic therapy for
metastatic disease.
5. Measurable disease according to RECIST v1.1.
6. An Eastern Cooperative Group (ECOG) performance status ≤ 1.
7. Adequate organ function.
8. Adequate recovery from toxicities related to prior treatments.
9. For patients with reproductive potential, a negative pregnancy test must be
confirmed and agreement to use highly effective method of contraceptive.
10. Willingness to comply with the scheduled visits, treatment plan, laboratory tests
and other study procedures.
Exclusion Criteria:
Patients will be excluded from the study if they meet any of the following criteria:
1. Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy.
2. Co-existing high-grade serous ovarian cancer or mixed histology.
3. Prior treatment with avutometinib, defactinib, or other FAK inhibitors.
4. History of prior malignancy with recurrence <3 years from the time of enrollment.
5. Major surgery within 4 weeks, minor surgery within 1 week, or palliative
radiotherapy within 1 week of the first dose of study intervention.
6. Symptomatic brain metastases requiring steroids or other interventions, known
leptomeningeal metastases, or spinal cord compression.
7. An active skin disorder that has required systemic therapy within one year of the
first dose of study intervention.
8. History of medically significant rhabdomyolysis.
9. For subjects with prior MEK or RAF exposure, Grade 4 toxicity is deemed related to
the MEK inhibitor.
10. Symptomatic bowel obstruction within 3 months of the first dose of study
intervention
11. Concurrent ocular disorders.
12. Concurrent heart disease or severe obstructive pulmonary disease.
13. Active or past medical history of interstitial lung disease/pneumonitis, including
drug-induced or radiation pneumonitis, pulmonary fibrosis, or adult respiratory
distress syndrome (ARDS).
14. Subjects with the inability to swallow oral medications.
15. History of hypersensitivity to any of the active agents or ingredients of study
intervention: peanut, soya, polyoxyl castor oil, etcetc.). Prior hypersensitivity to
anthracyclines or anthracenediones if the use of pegylated liposomal doxorubicin
(PLD) is planned.
16. Pregnant or breastfeeding.
17. Active, uncontrolled infection (bacterial, viral, or fungal) requiring systemic
therapy.
Gender:
Female
Gender based:
Yes
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
HonorHealth
Address:
City:
Phoenix
Zip:
85016
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kelly Fillbrant
Email:
kfillbrandt@honorhealth.com
Investigator:
Last name:
Lyndsay Willmott, MD
Email:
Principal Investigator
Facility:
Name:
University of Arkansas
Address:
City:
Little Rock
Zip:
72205
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kathryn Allen
Email:
KGAllen@uams.edu
Investigator:
Last name:
Heather Williams, MD
Email:
Principal Investigator
Facility:
Name:
UCLA Health
Address:
City:
Los Angeles
Zip:
90095
Country:
United States
Status:
Recruiting
Contact:
Last name:
Surya Nagesh
Email:
snagesh@mednet.ucla.edu
Investigator:
Last name:
Ritu Salani, MD
Email:
Principal Investigator
Facility:
Name:
University of California, San Francisco
Address:
City:
San Francisco
Zip:
94143
Country:
United States
Status:
Recruiting
Contact:
Last name:
Nathalie Halley
Email:
nathalie.halley2@ucsf.edu
Investigator:
Last name:
Jocelyn Chapman, MD
Email:
Principal Investigator
Facility:
Name:
Yale University
Address:
City:
New Haven
Zip:
06520
Country:
United States
Status:
Recruiting
Contact:
Last name:
Lisa Baker
Email:
lisa.baker@yale.edu
Investigator:
Last name:
Alessandro Santin, MD
Email:
Principal Investigator
Facility:
Name:
Florida Cancer Specialists - South
Address:
City:
Fort Myers
Zip:
33901
Country:
United States
Status:
Recruiting
Contact:
Last name:
Christina Caruso
Email:
Ccaruso@flcancer.com
Investigator:
Last name:
Elizabeth Guancial, MD
Email:
Principal Investigator
Facility:
Name:
Mount Sinai
Address:
City:
Miami Beach
Zip:
33140
Country:
United States
Status:
Recruiting
Contact:
Last name:
Antonio Ramirez Riderelli
Email:
Antonio.RamirezRiderelli@msmc.com
Investigator:
Last name:
Brian Slomovitz, MD
Email:
Principal Investigator
Facility:
Name:
AdventHealth
Address:
City:
Orlando
Zip:
32804
Country:
United States
Status:
Recruiting
Contact:
Last name:
Karla Hernandez-Cruz
Email:
Karla.Hernandez-Cruz@AdventHealth.com
Investigator:
Last name:
Robert Holloway, MD
Email:
Principal Investigator
Facility:
Name:
Florida Cancer Specialists Research East
Address:
City:
West Palm Beach
Zip:
33401
Country:
United States
Status:
Recruiting
Contact:
Last name:
Mary Jo Luser
Email:
maryjo.luser@flcancer.com
Investigator:
Last name:
Bradley Monk, MD
Email:
Principal Investigator
Facility:
Name:
Winship Cancer Institute at Emory University
Address:
City:
Atlanta
Zip:
30322
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ashley Trumball
Email:
ashley.lynn.trumbull@emory.edu
Investigator:
Last name:
Susan Modesitt, MD
Email:
Principal Investigator
Facility:
Name:
NorthShore University HealthSystem
Address:
City:
Evanston
Zip:
60201
Country:
United States
Status:
Recruiting
Contact:
Last name:
Michele Britto
Email:
mbritto@northshore.org
Investigator:
Last name:
Mary Tilley Jenkins-Vogel, MD
Email:
Principal Investigator
Facility:
Name:
Louisiana State University
Address:
City:
New Orleans
Zip:
70112
Country:
United States
Status:
Recruiting
Contact:
Last name:
Alex Yates
Email:
ayate2@lsuhsc.edu
Investigator:
Last name:
Amelia Jernigan, MD
Email:
Principal Investigator
Facility:
Name:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Address:
City:
Baltimore
Zip:
21287
Country:
United States
Status:
Recruiting
Contact:
Last name:
Faith Too
Email:
ftoo1@jhmi.edu
Contact backup:
Email:
HopkinsGynTrials@jhmi.edu
Investigator:
Last name:
Stephanie Gaillard, MD
Email:
Principal Investigator
Facility:
Name:
Karmanos Cancer Center
Address:
City:
Detroit
Zip:
48201
Country:
United States
Status:
Recruiting
Contact:
Last name:
Elizabeth Linnik
Email:
linnike@karmanos.org
Investigator:
Last name:
Robert Morris, MD
Email:
Principal Investigator
Facility:
Name:
Minnesota Oncology Hematology
Address:
City:
Minneapolis
Zip:
55404
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kayla McDonald
Email:
kayla.mcdonald1@usoncology.com
Investigator:
Last name:
Lauren Bollinger, MD
Email:
Principal Investigator
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Contact:
Last name:
Linda Odibo
Email:
odibol@wustl.edu
Investigator:
Last name:
Premal Thaker, MD
Email:
Principal Investigator
Facility:
Name:
Roswell Park Cancer Institute
Address:
City:
Buffalo
Zip:
14263
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kimberly Benczkowski
Email:
Kimberly.Benczkowski@RoswellPark.org
Investigator:
Last name:
Karen McLean, MD
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rachel Grisham
Phone:
646-888-4653
Investigator:
Last name:
Rachel Grisham, MD
Email:
Principal Investigator
Facility:
Name:
Atrium Health
Address:
City:
Charlotte
Zip:
28203
Country:
United States
Status:
Recruiting
Contact:
Last name:
Melani Terry
Email:
Melani.Terry@atriumhealth.org
Investigator:
Last name:
Erin Crane, MD
Email:
Principal Investigator
Facility:
Name:
Cleveland Clinic Foundation
Address:
City:
Cleveland
Zip:
44195
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jacqueline Ludwig
Email:
ludwigj@ccf.org
Investigator:
Last name:
Peter Rose, MD
Email:
Principal Investigator
Facility:
Name:
Ohio State
Address:
City:
Hilliard
Zip:
43026
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jordyn Burks
Email:
Jordyn.Burks@osumc.edu
Investigator:
Last name:
Christa Nagel, MD
Email:
Principal Investigator
Facility:
Name:
University of Oklahoma Medical Center
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Stephanie Chaney
Email:
stephanie-chaney@ouhsc.edu
Investigator:
Last name:
Christina Washington, MD
Email:
Principal Investigator
Facility:
Name:
Willamette Valley Cancer Institute
Address:
City:
Eugene
Zip:
97401
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jeanne Scahffer
Email:
jeanne.schaffer@usoncology.com
Investigator:
Last name:
Charles Anderson, MD
Email:
Principal Investigator
Facility:
Name:
Northwest Cancer Specialists
Address:
City:
Portland
Zip:
97227
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jennifer Thompson
Email:
Jennifer.Thompson@usoncology.com
Investigator:
Last name:
Erin Salinas, MD
Email:
Principal Investigator
Facility:
Name:
Asplundh Cancer Pavilion | Jefferson Health
Address:
City:
Philadelphia
Zip:
19090
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ashley Douglas
Email:
ashley.douglas.2@jefferson.edu
Investigator:
Last name:
Mitchell Edelson, MD
Email:
Principal Investigator
Facility:
Name:
Allegheny Health Network
Address:
City:
Pittsburgh
Zip:
15224
Country:
United States
Status:
Recruiting
Contact:
Last name:
Siobhan Guyach
Email:
siobhan.guyach@ahn.org
Investigator:
Last name:
Thomas Krivak, MD
Email:
Principal Investigator
Facility:
Name:
Texas Oncology Central
Address:
City:
Austin
Zip:
78731
Country:
United States
Status:
Recruiting
Contact:
Last name:
Michelle Owens
Email:
michelle.owens@usoncology.com
Investigator:
Last name:
Lynn Knowles, MD
Email:
Principal Investigator
Facility:
Name:
Texas Oncology-Fort Worth Cancer Center
Address:
City:
Fort Worth
Zip:
76104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Nori Sullivan
Email:
nori.sullivan@usoncology.com
Investigator:
Last name:
Noelle Cloven, MD
Email:
Principal Investigator
Facility:
Name:
Texas Oncology
Address:
City:
San Antonio
Zip:
78229
Country:
United States
Status:
Recruiting
Contact:
Last name:
Shannon Syring
Email:
shannon.syring@usoncology.com
Investigator:
Last name:
Antonio Santillan Gomez, MD
Email:
Principal Investigator
Facility:
Name:
Texas Oncology
Address:
City:
The Woodlands
Zip:
77380
Country:
United States
Status:
Recruiting
Contact:
Last name:
Christina Genthon
Email:
Christina.Genthon@usoncology.com
Contact backup:
Last name:
Sandra Thornton
Email:
Sandra.Thornton@usoncology.com
Investigator:
Last name:
Christine Lee, MD
Email:
Principal Investigator
Facility:
Name:
Texas Oncology
Address:
City:
Tyler
Zip:
75702
Country:
United States
Status:
Recruiting
Contact:
Last name:
Shelly Maxfield
Email:
shelly.maxfield@usoncology.com
Investigator:
Last name:
Anna M Priebe, MD
Email:
Principal Investigator
Facility:
Name:
Intermountain Medical Center
Address:
City:
Murray
Zip:
84107
Country:
United States
Status:
Recruiting
Contact:
Last name:
Stacy Howard
Email:
stacy.howard@imail.org
Investigator:
Last name:
Emily Prendergast, MD
Email:
Principal Investigator
Facility:
Name:
University of Virginia Health System
Address:
City:
Charlottesville
Zip:
22908
Country:
United States
Status:
Recruiting
Contact:
Last name:
Magnifique Irakoze
Email:
rve7xg@virginia.edu
Investigator:
Last name:
Kari Ring, MD
Email:
Principal Investigator
Facility:
Name:
Virginia Cancer Specialists, PC
Address:
City:
Gainesville
Zip:
20155
Country:
United States
Status:
Recruiting
Contact:
Last name:
Monica Cochrane
Email:
monica.cochrane@usoncology.com
Investigator:
Last name:
Robert Marsh, MD
Email:
Principal Investigator
Facility:
Name:
Prince of Wales Hospital
Address:
City:
Randwick
Zip:
2031
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Kaye Kongrak
Email:
Kamonwan.Kongrak@health.nsw.gov.au
Investigator:
Last name:
Yeh Chen Lee, MD
Email:
Principal Investigator
Facility:
Name:
Icon Cancer Centre Wesley
Address:
City:
Auchenflower
Zip:
4066
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Amy Morrow
Email:
researchwesley@icon.team
Investigator:
Last name:
Jeffrey Goh, MD
Email:
Principal Investigator
Facility:
Name:
Cancer Research South Australia
Address:
City:
Adelaide
Zip:
5000
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Vineet Kwatra, MD
Email:
vkwatra@crsa.au
Investigator:
Last name:
Meena Okera, MD
Email:
Principal Investigator
Facility:
Name:
Peter MacCallum Cancer Centre
Address:
City:
Melbourne
Zip:
3000
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Nicole Marsh
Email:
nicole.marsh@petermac.org
Investigator:
Last name:
Sumitra Ananda, MD
Email:
Principal Investigator
Facility:
Name:
Sir Charles Gairdner Hospital
Address:
City:
Nedlands
Zip:
6009
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Jolanta Damas
Email:
Jolanta.Damas1@health.wa.gov.au
Investigator:
Last name:
Tarek Meniawy, MD
Email:
Principal Investigator
Facility:
Name:
Princess Margaret Cancer Center
Address:
City:
Toronto
Zip:
M5G 1X6
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Valerie Bowering
Email:
valerie.bowering@uhn.ca
Investigator:
Last name:
Amit Oza, MD
Email:
Principal Investigator
Facility:
Name:
McGill University Health Centre
Address:
City:
Montreal
Zip:
H4A 3J1
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Phuong Nam Nathalie Nguyen
Email:
phuong-nam.nguyen@muhc.mcgill.ca
Investigator:
Last name:
Lucy Gilbert, MD
Email:
Principal Investigator
Facility:
Name:
Centre Hospitalier de l'Universite de Montreal (CHUM)
Address:
City:
Montréal
Zip:
H2X 0C1
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Nathalie Grenier
Email:
nathalie.grenier.chum@ssss.gouv.qc.ca
Investigator:
Last name:
Diane Provencher, MD
Email:
Principal Investigator
Facility:
Name:
Centre Hospitalier de Besançon
Address:
City:
Besançon
Zip:
25000
Country:
France
Status:
Recruiting
Contact:
Last name:
Ophélie Sivignon
Email:
osivignon@chu-besancon.fr
Investigator:
Last name:
Laura Mansi, MD
Email:
Principal Investigator
Facility:
Name:
Institut Curie
Address:
City:
Paris
Country:
France
Status:
Recruiting
Contact:
Last name:
Manuel Rodrigues, MD
Phone:
0033 1 56 24 56 42
Email:
manuel.rodrigues@curie.fr
Facility:
Name:
European Institute of Oncology (IEO)
Address:
City:
Milan
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Beatrice Rizzoli
Email:
Beatrice.rizzoli@ieo.it
Investigator:
Last name:
Nicoletta Columbo, MD
Email:
Principal Investigator
Facility:
Name:
H. Vall d´ Hebron
Address:
City:
Barcelona
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Olga Padros
Email:
opadros@vhio.net
Investigator:
Last name:
Ana Oaknin, MD
Email:
Principal Investigator
Facility:
Name:
H.U. Ramón y Cajal
Address:
City:
Madrid
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Iluminada Hernandez Blazquez
Email:
ihernandezb@salud.madrid.org
Investigator:
Last name:
Alfonso Cortes Salgado, MD
Email:
Principal Investigator
Facility:
Name:
Greater Glasgow and Clyde (GGC)
Address:
City:
Glasgow
Zip:
G120YN
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Ros Glasspool, MD
Email:
ros.glasspool@ggc.scot.nhs.uk
Investigator:
Last name:
Ros Glasspool, MD
Email:
Principal Investigator
Facility:
Name:
University of Edinburgh Cancer Research Centre
Address:
City:
Edinburgh
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Olga Demyanov
Email:
olga.demyanov@nhs.scot
Investigator:
Last name:
Charlie Gourley, MD
Email:
Principal Investigator
Facility:
Name:
Hope Cancer Trials Centre
Address:
City:
Leicester
Zip:
LE2 7LX
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Joey Wood, MD
Phone:
0116 258 5750
Email:
joey.wood@uhl-tr.nhs.uk
Investigator:
Last name:
Joey Wood
Email:
Principal Investigator
Facility:
Name:
University College London Hospitals NHS Foundation Trust
Address:
City:
London
Zip:
NW1 2PG
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Christian Paul Medina
Email:
christianpaul.medina@nhs.net
Contact backup:
Last name:
Shibani Nicum, MD
Email:
snicum@nhs.net
Investigator:
Last name:
Rowan Miller, MD
Email:
Principal Investigator
Facility:
Name:
Royal Marsden Hospital
Address:
City:
London
Zip:
SW7 3RP
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Kylie Fitch
Email:
Kylie.Fitch@rmh.nhs.uk
Investigator:
Last name:
Susana Banerjee, MD
Email:
Principal Investigator
Facility:
Name:
The Christie NHS Foundation Trust
Address:
City:
Manchester
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Linzi Davies
Email:
linzi.davies@nhs.net
Investigator:
Last name:
Andrew Clamp, MD
Email:
Principal Investigator
Facility:
Name:
Royal Marsden Hospital
Address:
City:
Sutton
Zip:
SM2 5PT
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Kylie Fitch
Email:
Kylie.Fitch@rmh.nhs.uk
Investigator:
Last name:
Susana Banerjee, MD
Email:
Principal Investigator
Start date:
March 18, 2024
Completion date:
February 9, 2031
Lead sponsor:
Agency:
Verastem, Inc.
Agency class:
Industry
Collaborator:
Agency:
GOG Foundation
Agency class:
Other
Collaborator:
Agency:
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Agency class:
Other
Collaborator:
Agency:
Australia New Zealand Gynaecological Oncology Group
Agency class:
Other
Source:
Verastem, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06072781
