Savolitinib in Treating Patients With MET Amplified Metastatic or Unresectable Colorectal Cancer

Stopped early · Phase 2

Conditions studied: Colorectal Carcinoma, Metastatic Colon Adenocarcinoma, Metastatic Rectal Adenocarcinoma, Stage III Colon Cancer AJCC v8, Stage III Rectal Cancer AJCC v8, Stage IIIA Colon Cancer AJCC v8, Stage IIIA Rectal Cancer AJCC v8, Stage IIIB Colon Cancer AJCC v8, Stage IIIB Rectal Cancer AJCC v8, Stage IIIC Colon Cancer AJCC v8, Stage IIIC Rectal Cancer AJCC v8, Stage IV Colon Cancer AJCC v8, Stage IV Rectal Cancer AJCC v8, Stage IVA Colon Cancer AJCC v8, Stage IVA Rectal Cancer AJCC v8, Stage IVB Colon Cancer AJCC v8, Stage IVB Rectal Cancer AJCC v8, Stage IVC Colon Cancer AJCC v8, Stage IVC Rectal Cancer AJCC v8, Unresectable Colon Adenocarcinoma, Unresectable Rectal Adenocarcinoma

In brief

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.

Key facts

Study ID

NCT03592641

Run by

National Cancer Institute (NCI)

People needed

5

Starts

2019-07-25

Expected to finish

2021-12-30

Last updated by the study team

2023-10-17

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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 × 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:
• Post-menopausal is defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments; women under the age of 50 years would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for the institution; or women with documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
• Male patients with female partner of childbearing potential should be willing to use barrier contraception during the study and for 6 months following discontinuation of study drug
• Ability to swallow and retain oral medications
• Ability to understand and the willingness to sign a written informed consent document

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
• Stroke or transient ischemic attack
• Known hypersensitivity to the active or inactive excipients of AZD6094
• Uncontrolled hypertension (blood pressure [BP] >= 150/95 mmHg despite medical therapy)
• Active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea grade >= 2, and malabsorption syndrome)
• Mean resting correct QT interval (Fridericia's correction formula [QTcF]) > 470 msec for women and > 450 msec for men on screening obtained from 3 electrocardiograms (ECGs)
• Any factors that may increase the risk of QTc prolongation such as chronic hypokalemia not correctable with supplements, congenital or familial long QT syndrome; or family history of unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medications known to prolong QT interval and cause Torsades de Pointes (TdP)
• Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiograms (ECGs), e.g. complete left bundle branch block, third degree heart block, second degree heart block, PR interval > 250 msec
• Major surgical procedures =< 28 days of beginning study drug or minor surgical procedures =< 7 days. No waiting is required following port-a-cath placement
• Serious underlying medical condition at the time of treatment that would impair the ability of the patient to receive protocol treatment
• Active hepatitis B (positive hepatitis b virus [HBV] surface antigen [HBsAg] result) or hepatitis C (hepatitis C virus [HCV]) infection. Patients with positive HCV antibody are eligible only if the polymerase chain reaction is negative for HCV ribonucleic acid (RNA). Patients with a past or resolved HBV infection are eligible if:

Where it is running

• Los Angeles County-USC Medical Center — Los Angeles, California, United States
• USC / Norris Comprehensive Cancer Center — Los Angeles, California, United States
• University of California Davis Comprehensive Cancer Center — Sacramento, California, United States
• Smilow Cancer Hospital-Derby Care Center — Derby, Connecticut, United States
• Smilow Cancer Hospital Care Center-Fairfield — Fairfield, Connecticut, United States
• Smilow Cancer Hospital Care Center - Guilford — Guilford, Connecticut, United States
• Smilow Cancer Hospital Care Center at Saint Francis — Hartford, Connecticut, United States
• Smilow Cancer Center/Yale-New Haven Hospital — New Haven, Connecticut, United States
• Yale University — New Haven, Connecticut, United States
• Yale-New Haven Hospital North Haven Medical Center — North Haven, Connecticut, United States
• Smilow Cancer Hospital-Orange Care Center — Orange, Connecticut, United States
• Smilow Cancer Hospital-Torrington Care Center — Torrington, Connecticut, United States
• Smilow Cancer Hospital Care Center-Trumbull — Trumbull, Connecticut, United States
• Smilow Cancer Hospital-Waterbury Care Center — Waterbury, Connecticut, United States
• Smilow Cancer Hospital Care Center - Waterford — Waterford, Connecticut, United States
• University of Florida Health Science Center - Gainesville — Gainesville, Florida, United States
• Northwestern University — Chicago, Illinois, United States
• University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States
• University of Kansas Clinical Research Center — Fairway, Kansas, United States
• University of Kansas Cancer Center — Kansas City, Kansas, United States
• University of Kansas Hospital-Westwood Cancer Center — Westwood, Kansas, United States
• University of Kentucky/Markey Cancer Center — Lexington, Kentucky, United States
• Siteman Cancer Center at Saint Peters Hospital — City of Saint Peters, Missouri, United States
• Siteman Cancer Center at West County Hospital — Creve Coeur, Missouri, United States
• Washington University School of Medicine — St Louis, Missouri, United States

Full record on ClinicalTrials.gov

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