Program Status
Active, not recruitingPhase
Phase 2Prior Immunotherapy Allowed
NoCRC-directed Trial
YesDrugs
Bevacizumab, FOLFIRI, FOLFOX, OnvansertibTags
MSS/ MMRpComments
Onvansertib is a highly selective PLK1 inhibitor. PLK1 is a protein which serves as a master regulator of cancer cell division.
It is for patients who are about to start treatment for their metastatic cancer; that is, for those who have not received first line chemotherapy in the metastatic setting.
KRAS or NRAS mutated metastatic CRC required. Patients with BRAF mutation are excluded. Only for MSS.
No prior bevacizumab (Avastin) allowed.
Patients will be randomized to receive standard of care (Folfox or Folfiri with bevacizumab), or the experimental agent onvansertib (oral, a pill), at two different doses, added to standard of care (Folfox or Folfiri with bevacuzumab).
Data from a previos trial (2022) show that the the addition of the PLK1 inhibitor onvansertib to FOLFIRI/bevacizumab shows very promising efficacy results with response rates of over 30% and PFS over 9 months in second-line mCRC KRAS-mutant colon cancer. The treatment is well-tolerated.
Onvansertib overcomes irinotecan resistance in RAS-mutated metastatic CRC
Helpful Links
https://www.annalsofoncology.org/article/S0923-7534(22)02355-9/fulltext Onvansertib in Combination with FOLFIRI and Bevacizumab in Second-Line Treatment of KRAS-Mutant Metastatic Colorectal Cancer: A Phase Ib Clinical Study Cardiff Oncology: Scientific Presentations Posters| Location | Location Status |
|---|---|
| United States | |
|
Mayo Clinic - Arizona Phoenix, Arizona 85054 |
Active, not recruiting |
|
The University of Arizona Cancer Center Tucson, Arizona 85724 |
Active, not recruiting |
|
St. Bernards Medical Center Jonesboro, Arkansas 72401 |
Active, not recruiting |
|
Highlands Oncology Group Springdale, Arkansas 72762 |
Active, not recruiting |
|
Pacific Cancer Medical Center Anaheim, California 92801 |
Active, not recruiting |
|
Comprehensive Blood and Cancer Center - Bakersfield Bakersfield, California 93309 |
Active, not recruiting |
|
Orange Coast Memorial Medical Center Fountain Valley, California 92708 |
Active, not recruiting |
|
UC San Diego Moores Cancer Center La Jolla, California 92037 |
Active, not recruiting |
|
Norris Comprehensive Cancer Center Los Angeles, California 90089 |
Active, not recruiting |
|
UCLA Department of Medicine-Hematology/Oncology Los Angeles, California 90095 |
Active, not recruiting |
|
Sharp Memorial Hospital San Diego, California 92123 |
Active, not recruiting |
|
Torrance Memorial Physician Network - Cancer Care and Infusion Center Torrance, California 90505 |
Active, not recruiting |
|
PIH Health Whittier, California 90602 |
Active, not recruiting |
|
Memorial Cancer Institute Hollywood, Florida 33021 |
Active, not recruiting |
|
Mayo Clinic - Florida Jacksonville, Florida 32224 |
Active, not recruiting |
|
Cleveland Clinic Martin Health Stuart, Florida 34994 |
Active, not recruiting |
|
Kaiser Permanente Honolulu, Hawaii 96819 |
Active, not recruiting |
|
Fort Wayne Medical Oncology and Hematology Fort Wayne, Indiana 46804 |
Active, not recruiting |
|
The University of Kansas Cancer Center - Westwood Westwood, Kansas 66205 |
Active, not recruiting |
|
Cancer Center of Kansas Wichita, Kansas 67214 |
Active, not recruiting |
|
Cancer & Hematology Centers of Western Michigan - Lemmen-Holton Cancer Pavilion Grand Rapids, Michigan 49503 |
Active, not recruiting |
|
Mayo Clinic Cancer Center Rochester, Minnesota 55905 |
Active, not recruiting |
|
Saint Luke's Hospital Kansas City, Missouri 64111 |
Active, not recruiting |
|
Washington University School of Medicine Center for Advanced Medicine Saint Louis, Missouri 63110 |
Active, not recruiting |
|
CCCN Las Vegas, Nevada 89119 |
Active, not recruiting |
|
Manhattan Hematology Oncology (MHO) Research Foundation, Inc. New York, New York 10016 |
Active, not recruiting |
|
Trihealth Kenwood Cincinnati, Ohio 45242 |
Active, not recruiting |
|
University Hospitals Cleveland Medical Center Cleveland, Ohio 44106 |
Active, not recruiting |
|
Cleveland Clinic Cleveland, Ohio 44195 |
Active, not recruiting |
|
The Ohio State University Wexner Medical Center Columbus, Ohio 43210 |
Active, not recruiting |
|
Oregon Health and Science University Portland, Oregon 97239 |
Active, not recruiting |
|
Lehigh Valley Health Network Allentown, Pennsylvania 18103 |
Active, not recruiting |
|
West Cancer Clinic Germantown, Tennessee 38138 |
Active, not recruiting |
|
Oncology Consultants, PA Houston, Texas 77024 |
Active, not recruiting |
|
MD Anderson Cancer Center Houston, Texas 77030 |
Active, not recruiting |
|
Utah Cancer Specialists Salt Lake City, Utah 84124 |
Active, not recruiting |
|
University of Virginia Charlottesville, Virginia 22908 |
Active, not recruiting |
|
Inova Schar Cancer Institute Fairfax, Virginia 22031 |
Active, not recruiting |
|
VCU Massey Cancer Center Richmond, Virginia 23298 |
Active, not recruiting |
|
Virginia Mason Medical Center Seattle, Washington 98101 |
Active, not recruiting |
|
ThedaCare Regional Cancer Center Appleton, Wisconsin 54911 |
Active, not recruiting |
Inclusion Criteria
Inclusion Criteria:
* Histologically confirmed metastatic colorectal cancer.
* Documented KRAS or NRAS mutation.
* No previous systemic therapy in the metastatic setting.
* Participants must be willing to submit archival tissue or undergo fresh biopsy.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Women of childbearing potential must use contraception or take measures to avoid pregnancy.
* Imaging computed tomography (CT) or magnetic resonance imaging (MRI) of chest/abdomen/pelvis and other scans as necessary to document all sites of disease performed within 28 days prior to the first dose of onvansertib.
* Must have acceptable organ function
Exclusion Criteria
Exclusion Criteria:
* Concomitant KRAS or NRAS and BRAF-V600 mutation or microsatellite instability high/deficient mismatch repair.
* Prior treatment with a VEGF inhibitor, including bevacizumab or biosimilars.
* Previous oxaliplatin treatment within 12 months prior to randomization, when arm open.
* Known dihydropyrimidine dehydrogenase (DPD) deficiency.
* Anticancer chemotherapy or biologic therapy administered within 28 days prior to the first dose of study drug.
* Untreated or symptomatic brain metastasis.
* Gastrointestinal (GI) disorder(s) that would significantly impede the absorption of an oral agent.
* Unable or unwilling to swallow study drug.
* Uncontrolled intercurrent illness.
* Known hypersensitivity to fluoropyrimidine or leucovorin, irinotecan, or oxalipatin.
* Abnormal glucuronidation of bilirubin; known Gilbert's syndrome.
* Use of strong CYP3A4 or CYP2C19 inhibitors or strong CYP3A4 inducers.
* QTc >470
