Colon Cancer Clinical Trial

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

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.

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Full Description

PRIMARY OBJECTIVE:

I. To estimate the objective response rate (ORR) of savolitinib in patients with MET amplified metastatic colorectal cancer (CRC).

SECONDARY OBJECTIVES:

I. To describe the clinical activity (duration of response, progression free survival [PFS]) of savolitinib in patients with MET amplified metastatic CRC.

II. To describe the toxicities of savolitinib in patients with MET amplified metastatic CRC.

III. To explore the effect of RAS mutation status on response to savolitinib. IV. To explore any correlation between tissue and blood based biomarkers and clinical outcomes.

OUTLINE:

Patients receive savolitinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, and then every 12 weeks thereafter for up to 2 years.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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:

Negative for HBsAg and positive for hepatitis B core antibody [anti-HBc] OR
Positive for HBsAg, but for > 6 months have had normal transaminases and HBV DNA levels between 0-2000 IU/ml (inactive carrier state) and willing to start and maintain antiviral treatment for at least the duration of the study OR
HBV DNA levels > 2000 IU/ml but on prophylactic antiviral treatment for the past 3 months and will maintain the antiviral treatment during the study

Known serious active infection requiring antibiotic, antiviral or antifungal therapy. Human immunodeficiency virus (HIV)-positive patients are eligible only if meeting ALL criteria below:

No history of acquired immunodeficiency syndrome (AIDS)-defining conditions
Has been on the current highly active antiretroviral therapy (HAART) regimen for the past 3 months and will remain on the same regimen during the study
Current HAART regimen has a low potential for drug-drug interaction with the study drug
HIV viral load consistently below detectable limit for the past 3 months
CD4 count consistently > 200 cells/mm^3 for the past 3 months
Presence of other active cancers, or history of treatment for invasive cancer, within the last 5 years. Patients with stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely (less than 5% probability) to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of non-melanoma skin cancer
Psychiatric illness/social situations that would limit compliance with study requirements. Patients with impaired decision-making capacity who have a close caregiver or legal guardian are also eligible with the consent of the caregiver/guardian
Judgment by the investigator that the patients should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements

Study is for people with:

Colon Cancer

Phase:

Phase 2

Estimated Enrollment:

5

Study ID:

NCT03592641

Recruitment Status:

Active, not recruiting

Sponsor:

National Cancer Institute (NCI)

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There are 30 Locations for this study

See Locations Near You

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 - Guiford
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 West County Hospital
Creve Coeur Missouri, 63141, United States
Washington University School of Medicine
Saint Louis Missouri, 63110, United States
Siteman Cancer Center-South County
Saint Louis Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
Saint Louis Missouri, 63136, United States
Siteman Cancer Center at Saint Peters Hospital
Saint Peters Missouri, 63376, 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

How clear is this clinincal trial information?

Study is for people with:

Colon Cancer

Phase:

Phase 2

Estimated Enrollment:

5

Study ID:

NCT03592641

Recruitment Status:

Active, not recruiting

Sponsor:


National Cancer Institute (NCI)

How clear is this clinincal trial information?

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