Trial Title:
Study of Onvansertib in Combination With FOLFIRI and Bevacizumab Versus FOLFIRI and Bevacizumab for Second Line Treatment of Metastatic Colorectal Cancer in Participants With a Kirsten Rat Sarcoma Virus Gene (KRAS) or Neuroblastoma-RAS (NRAS) Mutation
NCT ID:
NCT05593328
Condition:
Colorectal Cancer
Metastatic Colorectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Bevacizumab
Onvansertib
Conditions: Keywords:
Colorectal Cancer
Metastatic Colorectal Cancer
KRAS Mutation
NRAS Mutation
Onvansertib
FOLFIRI
Bevacizumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Onvansertib
Description:
Oral capsule
Arm group label:
Onvansertib 20 mg + Standard of Care (SOC)
Arm group label:
Onvansertib 30 mg + Standard of Care (SOC)
Intervention type:
Drug
Intervention name:
FOLFIRI
Description:
FOLFIRI (irinotecan + fluorouracil [5-FU] + leucovorin) as intravenous (IV) infusion
Arm group label:
Onvansertib 20 mg + Standard of Care (SOC)
Arm group label:
Onvansertib 30 mg + Standard of Care (SOC)
Arm group label:
Standard of Care (SOC)
Intervention type:
Drug
Intervention name:
Bevacizumab
Description:
IV infusion
Arm group label:
Onvansertib 20 mg + Standard of Care (SOC)
Arm group label:
Onvansertib 30 mg + Standard of Care (SOC)
Arm group label:
Standard of Care (SOC)
Summary:
The primary objective of this study is to assess the efficacy of 2 different doses of
onvansertib in combination with a chemotherapy regimen of irinotecan, fluorouracil
[5-FU], and leucovorin (FOLFIRI) and bevacizumab for treatment of confirmed metastatic
and/or unresectable colorectal cancer (CRC) in participants with a kirsten rat sarcoma
virus gene (KRAS) or neuroblastoma-RAS (NRAS) mutation who have progressed on an
oxaliplatin/fluoropyrimidinebased regimen in the first-line setting.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Histologically confirmed metastatic and/or unresectable colorectal cancer (CRC).
2. Documentation of a kirsten rat sarcoma virus gene (KRAS) or neuroblastoma-RAS (NRAS)
mutation in exon 2, 3, or 4 in primary tumor or metastasis, assessed by a Clinical
Laboratory Improvement Amendments (CLIA)-certified laboratory.
3. Age ≥ 18 years.
4. Participants with tumors that have progressed on an
oxaliplatin/fluoropyrimidine--based regimen with or without bevacizumab.
1. Participants must have had systemic therapy within 180 days of the screening
visit.
2. Participants must have, at any time previously, received oxaliplatin-based
chemotherapy with or without bevacizumab (≥ 6 weeks in duration).
3. Participants who received oxaliplatin/fluoropyrimidine-based neoadjuvant,
adjuvant, and/or fluoropyrimidine maintenance or adjuvant therapy and have
disease recurrence or progression > 6 months from their last dose of
oxaliplatin will be required to have received
oxaliplatin/fluoropyrimidine-based therapy with or without bevacizumab as
first-line treatment for metastatic disease.
4. Participants who received an oxaliplatin-based regimen in the first-line
setting and discontinued oxaliplatin because of toxicity or who received
oxaliplatin for maintenance therapy are eligible as long as progression
occurred < 6 months after the last dose of oxaliplatin therapy for advanced
metastatic disease. It is recommended that these participants be re-challenged
(if feasible) with oxaliplatin/fluoropyrimidine therapy and subsequently
progress prior to eligibility. Participants with oxaliplatin-related neuropathy
or oxaliplatin infusion-related hypersensitivity that cannot be rechallenged
with oxaliplatin are eligible.
5. Participants must not have received prior treatment with irinotecan.
6. FOLFIRI therapy is appropriate for the participant as determined by the
Investigator.
7. Imaging computed tomography (CT) or magnetic resonance imaging (MRI) of
chest/abdomen/pelvis or other scans as necessary to document all sites of disease
performed within 28 days prior to the first dose of onvansertib. Only participants
with measurable disease as defined per Response Evaluation Criteria in Solid Tumors
Version 1.1 (RECIST v1.1) are eligible for enrollment. CT is the preferred imaging
modality, but MRI is also accepted. All subsequent scans must consistently use the
same imaging modality for comparison with the Screening scan throughout the study.
8. Must have acceptable organ function
9. Signed informed consent to provide blood sample(s) for specific correlative assays
Exclusion Criteria:
1. Concomitant KRAS or NRAS and BRAF-V600 mutation or Microsatellite Instability
High/Deficient Mismatch Repair (MSI-H/dMMR).
2. Anti-cancer chemotherapy or biologic therapy administered within 28 days prior to
the first dose of study drug. The exception is a single dose of radiation up to 8
Gray (equal to 800 RAD) with palliative intent for pain control up to 14 days before
enrollment, provided it is not the target lesion.
3. More than 1 prior chemotherapy regimen administered in the metastatic setting.
4. Major surgery within 6 weeks prior to enrollment.
5. Untreated or symptomatic brain metastasis.
6. Gastrointestinal (GI) disorder(s) that, in the opinion of the Investigator, would
significantly impede the absorption of an oral agent (e.g., intestinal occlusion,
active Crohn's disease, ulcerative colitis, extensive gastric and small intestine
resection).
7. Unable or unwilling to swallow study drug.
8. Known hypersensitivity to fluoropyrimidine or leucovorin.
9. Known hypersensitivity to irinotecan.
10. Abnormal glucuronidation of bilirubin; known Gilbert's syndrome.
11. QT interval:
1. Fridericia's correction (QTcF) > 470 milliseconds. The QTcF should be
calculated as the arithmetic mean of the QTcF on triplicate electrocardiograms
(ECGs). In the case of potentially correctible causes of QT prolongation that
are readily corrected (e.g., medications, hypokalemia), the triplicate ECG may
be repeated once during Screening and that result may be used to determine
eligibility.
2. Planned concomitant use of medications known to prolong the QT/QTc interval
according to institutional guidelines.
3. Presence of risk factors for torsade de pointes, including family history of
Long QT Syndrome or uncorrected hypokalemia.
12. Use of strong cytochrome P450 3A4 (CYP3A4) or cytochrome P450 2C19 (CYP2C19)
inhibitors or strong CYP3A4 inducers. Participants currently receiving these agents
who can be switched to alternate therapy are not excluded. Inhibitors should be
stopped at least 1 week prior to the first dose of protocol therapy and inducers
should be stopped at least 2 weeks prior to initiation of protocol therapy.
13. The following are exclusion criteria for bevacizumab:
1. History of cardiac disease: Congestive heart failure (CHF) Class II or higher
according to the New York Heart Association (NYHA); active coronary artery
disease, myocardial infarction within 6 months prior to study entry;
unevaluated new onset angina within 3 months or unstable angina (angina
symptoms at rest) or cardiac arrhythmias requiring anti-arrhythmic therapy,
with the exception of participants who have been receiving therapy and are
deemed by the Investigator to have stable/controlled disease.
2. Current uncontrolled hypertension (systolic blood pressure >150 mmHg or
diastolic blood pressure >90 mmHg despite optimal medical management) and prior
history of hypertensive crisis or hypertensive encephalopathy.
3. History of arterial thrombotic or embolic events (within 6 months prior to
study entry).
4. Significant vascular disease (eg, aortic aneurysm, aortic dissection,
symptomatic peripheral vascular disease).
5. Evidence of bleeding diathesis or clinically significant coagulopathy.
6. Major surgical procedure (including open biopsy, significant traumatic injury,
etc) within 28 days, or anticipation of the need for major surgical procedure
during the study, and minor surgical procedure (excluding placement of a
vascular access device) within 7 days prior to study enrollment.
7. Proteinuria at Screening as demonstrated by urinalysis with proteinuria ≥2+
(participants discovered to have ≥2+ proteinuria on dipstick urinalysis at
baseline should undergo a 24-hour urine collection and must demonstrate ≤1 g of
protein in 24 hours to be eligible).
8. Abdominal fistula, gastrointestinal perforation, peptic ulcer, or
intra-abdominal abscess within the past 6 months.
9. Ongoing serious, non-healing wound, ulcer, or bone fracture
10. Known hypersensitivity to any component of bevacizumab
11. History of reversible posterior leukoencephalopathy syndrome
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic in Arizona - Phoenix Campus
Address:
City:
Phoenix
Zip:
85054
Country:
United States
Facility:
Name:
Central Arkansas Radiation Therapy Institute - Cancer Center
Address:
City:
Little Rock
Zip:
72205-6523
Country:
United States
Facility:
Name:
Pacific Cancer Medical Center
Address:
City:
Anaheim
Zip:
92801
Country:
United States
Facility:
Name:
Comprehensive Blood and Cancer Center - Bakersfield
Address:
City:
Bakersfield
Zip:
93309
Country:
United States
Facility:
Name:
Cancer and Blood Specialty Clinic
Address:
City:
Los Alamitos
Zip:
90720
Country:
United States
Facility:
Name:
Norris Comprehensive Cancer Center
Address:
City:
Los Angeles
Zip:
90033
Country:
United States
Facility:
Name:
UCI Health - Chao Family Comprehensive Cancer Center
Address:
City:
Orange
Zip:
92868
Country:
United States
Facility:
Name:
UCLA Health - Santa Monica Parkside Cancer Care
Address:
City:
Santa Monica
Zip:
90404
Country:
United States
Facility:
Name:
Torrance Memorial Physician Network - Cancer Care and Infusion Center
Address:
City:
Torrance
Zip:
90505
Country:
United States
Facility:
Name:
PIH Health
Address:
City:
Whittier
Zip:
90602
Country:
United States
Facility:
Name:
Mayo Clinic - Jacksonville
Address:
City:
Jacksonville
Zip:
32224
Country:
United States
Facility:
Name:
Memorial Hospital West
Address:
City:
Pembroke Pines
Zip:
33028
Country:
United States
Facility:
Name:
Cancer & Hematology Centers of Western Michigan - Lemmen-Holton Cancer Pavilion
Address:
City:
Grand Rapids
Zip:
49503
Country:
United States
Facility:
Name:
Mayo Clinic - Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Facility:
Name:
Washington University School of Medicine Center for Advanced Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Facility:
Name:
Nebraska Cancer Specialists - Midwest Cancer Center - Legacy
Address:
City:
Omaha
Zip:
68130
Country:
United States
Facility:
Name:
Englewood Health
Address:
City:
Englewood
Zip:
07631
Country:
United States
Facility:
Name:
San Juan Oncology Associates
Address:
City:
Farmington
Zip:
87401
Country:
United States
Facility:
Name:
Manhattan Hematology Oncology Associates
Address:
City:
New York
Zip:
10016
Country:
United States
Facility:
Name:
Gabrail Cancer and Research Center
Address:
City:
Canton
Zip:
44718
Country:
United States
Facility:
Name:
Trihealth Kenwood
Address:
City:
Cincinnati
Zip:
45236
Country:
United States
Facility:
Name:
University Hospitals Cleveland Medical Center
Address:
City:
Cleveland
Zip:
44106
Country:
United States
Facility:
Name:
West Cancer Center - East Campus
Address:
City:
Germantown
Zip:
38138
Country:
United States
Facility:
Name:
University of Texas MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Facility:
Name:
Utah Cancer Specialists
Address:
City:
Salt Lake City
Zip:
84106
Country:
United States
Facility:
Name:
University of Virginia School of Medicine
Address:
City:
Charlottesville
Zip:
22903
Country:
United States
Facility:
Name:
Inova Schar Cancer Institute
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Start date:
March 17, 2023
Completion date:
April 2026
Lead sponsor:
Agency:
Cardiff Oncology
Agency class:
Industry
Source:
Cardiff Oncology
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05593328
