Study Stopped
Inadequate accrual rate
Savolitinib in Treating Patients With MET Amplified Metastatic or Unresectable Colorectal Cancer
A Phase 2 Study of Savolitinib in Subjects With MET Amplified Metastatic Colorectal Cancer
4 other identifiers
interventional
5
1 country
33
Brief Summary
This phase II trial studies how well savolitinib works in treating patients with MET amplified colorectal cancer that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Savolitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Jul 2019
33 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 17, 2018
CompletedFirst Posted
Study publicly available on registry
July 19, 2018
CompletedStudy Start
First participant enrolled
July 25, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 31, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
December 30, 2021
CompletedResults Posted
Study results publicly available
August 8, 2023
CompletedOctober 17, 2023
September 1, 2023
2 years
July 17, 2018
July 20, 2023
September 22, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Objective Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Objective response rate is calculated as the number of people with a complete or partial response divided by the total number of people treated. Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
From start of treatment until documented progression of disease (up to 4 months)
Secondary Outcomes (1)
Months of Progression-Free Survival (PFS)
From start of treatment until documented progression of disease (up to 4 months)
Study Arms (1)
Treatment (savolitinib)
EXPERIMENTALPatients receive savolitinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed adenocarcinoma of the colon or rectum that is metastatic and/or unresectable
- Documented wild-type in KRAS and NRAS (codons 12, 13, 59, 61, 117, and 146) and in BRAF codon 600, based on tumor tissue taken from primary or metastatic site prior to anti-EGFR antibody treatment
- At least one site of disease that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
- MET amplification detected by the Guardant360 circulating free deoxyribonucleic acid (cfDNA) screening assay (MET copy number \>= 2.2)
- Clinical or radiographic progression on treatments containing a fluoropyrimidine (e.g., 5- fluorouracil or capecitabine), oxaliplatin, irinotecan, and an anti-VEGF monoclonal antibody (bevacizumab, ziv-aflibercept) or anti-VEGFR monoclonal antibody (ramucirumab), and an anti-PD1 monoclonal antibody (nivolumab or pembrolizumab) for patients with microsatellite instability (MSI)-high/mismatch repair (MMR) deficient tumors, or the treatments were not tolerated or contraindicated
- Clinical or radiographic progression on prior anti-EGFR antibody therapy (either panitumumab or cetuximab)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky \>= 80%)
- Absolute neutrophil count (ANC) \>= 1,500/mcL
- Hemoglobin (Hgb) \>= 9 g/dL (no transfusion in the past 2 weeks)
- Platelets \>= 100,000/mcL (no transfusion in the past 10 days)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x the institutional upper limit of normal (ULN) with total bilirubin (TBL) =\< 1 x ULN OR
- Total bilirubin (TBL) \> ULN =\<1.5 Ă— ULN with ALT and AST =\< 1x ULN
- Glomerular filtration rate (GFR) \>= 60 mL/min/1.73 m\^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m\^2
- International normalization ratio (INR) \< 1.5 x ULN and activated partial thromboplastin time (aPTT) \< 1.5 x ULN unless patients are receiving therapeutic anticoagulation which affects these parameters
- Females of childbearing potential should be willing to use adequate contraceptive measures, should not be breast feeding, and must have a negative pregnancy test if of childbearing potential or must have evidence of non-childbearing potential by fulfilling one of the following criteria at screening:
- +4 more criteria
You may not qualify if:
- Cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g. cytokines or antibodies) within 3 weeks of first dose of study treatment
- Not recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =\< grade 1 from adverse events due to all prior anti-cancer therapies except alopecia, oxaliplatin-related neuropathy, and other non-clinically significant adverse events
- Any other investigational agents within 21 days before the first dose of study treatment
- Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered =\< 28 days or limited field radiation for palliation =\< 7 days prior to starting study drug or has not recovered from side effects of such therapy
- Known brain metastases. (Radiated or resected lesions are permitted, provided the lesions are fully treated and inactive, patient is asymptomatic, and no steroids have been administered for at least 30 days)
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to savolitinib
- Prior treatment with a small molecule inhibitor of c-MET or monoclonal antibody against c-MET or HGF
- Any of the following concurrent medication use:
- Herbal preparations/medications are not allowed throughout the study. These herbal medications include, but are not limited to: St. John's wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (dhea), yohimbe, saw palmetto, and ginseng. Patients should stop using these herbal medications 7 days prior to first dose of study drug (three weeks for St. John's wort)
- Patients receiving or requiring strong inducers or strong inhibitors of CYP3A4, strong inhibitors of CYP1A2, or CYP3A4 substrates which have a narrow therapeutic range within 2 weeks of the first dose of study treatment (3 weeks for St John's wort) will be excluded
- Concomitant use of drugs that are known to be strong inhibitors of CYP3A4 or CYP1A2 is not permitted during the trial or must be stopped at least 2 weeks prior to receiving the first dose of savolitinib
- Any of the following cardiac disease currently or within the last 6 months:
- Unstable angina pectoris
- Congestive heart failure (New York Heart Association \[NYHA\]) \>= grade II
- Acute myocardial infarction
- +22 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (33)
Los Angeles County-USC Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Smilow Cancer Hospital-Derby Care Center
Derby, Connecticut, 06418, United States
Smilow Cancer Hospital Care Center-Fairfield
Fairfield, Connecticut, 06824, United States
Smilow Cancer Hospital Care Center - Guilford
Guilford, Connecticut, 06437, United States
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut, 06105, United States
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, 06510, United States
Yale University
New Haven, Connecticut, 06520, United States
Yale-New Haven Hospital North Haven Medical Center
North Haven, Connecticut, 06473, United States
Smilow Cancer Hospital-Orange Care Center
Orange, Connecticut, 06477, United States
Smilow Cancer Hospital-Torrington Care Center
Torrington, Connecticut, 06790, United States
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, 06611, United States
Smilow Cancer Hospital-Waterbury Care Center
Waterbury, Connecticut, 06708, United States
Smilow Cancer Hospital Care Center - Waterford
Waterford, Connecticut, 06385, United States
University of Florida Health Science Center - Gainesville
Gainesville, Florida, 32610, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
University of Kansas Clinical Research Center
Fairway, Kansas, 66205, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
NYU Winthrop Hospital
Mineola, New York, 11501, United States
Bellevue Hospital Center
New York, New York, 10016, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Parkland Memorial Hospital
Dallas, Texas, 75235, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
Related Publications (1)
Jia J, Moyer A, Lowe M, Bolch E, Kortmansky J, Cho M, Lenz HJ, Kalyan A, Niedzwiecki D, Strickler JH. A Phase 2 study of Savolitinib in Patients with MET Amplified Metastatic Colorectal Cancer. J Gastrointest Cancer. 2024 Dec 9;56(1):29. doi: 10.1007/s12029-024-01156-x.
PMID: 39652198DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- John Strickler, MD
- Organization
- Duke University Medical Center
Study Officials
- PRINCIPAL INVESTIGATOR
John H Strickler
Duke University - Duke Cancer Institute LAO
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 17, 2018
First Posted
July 19, 2018
Study Start
July 25, 2019
Primary Completion
July 31, 2021
Study Completion
December 30, 2021
Last Updated
October 17, 2023
Results First Posted
August 8, 2023
Record last verified: 2023-09
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page