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Colorectal CarcinomaPhase 2NCT03592641

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

A Phase 2 study testing Savolitinib in people with Colorectal Carcinoma and Metastatic Colon Adenocarcinoma, run by National Cancer Institute (NCI) at 33 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Savolitinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
33 sitesUnited States
Study dates
25 Jul 2019to 30 Dec 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

33 sites in 1 country.

33 sites in 1 country

United States33 sites

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • Parkland Memorial Hospital

    Dallas, Texas, 75235

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Smilow Cancer Hospital-Derby Care Center

    Derby, Connecticut, 06418

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Smilow Cancer Hospital Care Center-Fairfield

    Fairfield, Connecticut, 06824

  • University of Kansas Clinical Research Center

    Fairway, Kansas, 66205

  • University of Florida Health Science Center - Gainesville

    Gainesville, Florida, 32610

  • Smilow Cancer Hospital Care Center - Guilford

    Guilford, Connecticut, 06437

  • Smilow Cancer Hospital Care Center at Saint Francis

    Hartford, Connecticut, 06105

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • Los Angeles County-USC Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • NYU Winthrop Hospital

    Mineola, New York, 11501

  • Smilow Cancer Center/Yale-New Haven Hospital

    New Haven, Connecticut, 06510

  • Yale University

    New Haven, Connecticut, 06520

  • Bellevue Hospital Center

    New York, New York, 10016

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

  • Yale-New Haven Hospital North Haven Medical Center

    North Haven, Connecticut, 06473

  • Smilow Cancer Hospital-Orange Care Center

    Orange, Connecticut, 06477

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

  • Siteman Cancer Center at Christian Hospital

    St Louis, Missouri, 63136

  • Smilow Cancer Hospital-Torrington Care Center

    Torrington, Connecticut, 06790

  • Smilow Cancer Hospital Care Center-Trumbull

    Trumbull, Connecticut, 06611

  • Smilow Cancer Hospital-Waterbury Care Center

    Waterbury, Connecticut, 06708

  • Smilow Cancer Hospital Care Center - Waterford

    Waterford, Connecticut, 06385

  • University of Kansas Hospital-Westwood Cancer Center

    Westwood, Kansas, 66205

Other trials in United States

About this study

Official title: A Phase 2 Study of Savolitinib in Subjects With MET Amplified Metastatic Colorectal Cancer

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.

Read the detailed description

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

  1. 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.

Being tested
Savolitinib
Medical subject headings
Colorectal Neoplasms, Colonic Neoplasms, Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SavolitinibDrug

    Also called AZD 6094, AZD6094, HMPL-504, Volitinib

    Given PO

Study groups in NCT03592641
Study groupRoleWhat they receive
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.
Receives: Drug: Savolitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: From start of treatment until documented progression of disease (up to 4 months)

Secondary outcomes (1)

  1. Months of Progression-Free Survival (PFS)

    Progression-free survival is defined as the duration of time from start of treatment until clinical or radiographic progression or death, whichever occurs first. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

    Measured: From start of treatment until documented progression of disease (up to 4 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jul 2018
  2. Study start25 Jul 2019
  3. Primary completion31 Jul 2021
  4. Study completion30 Dec 2021

Why it stopped: Inadequate accrual rate

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03592641
Sponsor's protocol ID
NCI-2018-01463
Other IDs
NCI-2018-01463, NCI-10181, 10181, 10181, UM1CA186704
Status last verified
Sep 2023
First submitted
17 Jul 2018
Last updated
17 Oct 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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

Publications

  • 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.

    PubMed 39652198

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Savolitinib in people with Colorectal Carcinoma and Metastatic Colon Adenocarcinoma, run by National Cancer Institute (NCI) at 33 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) (time frame: From start of treatment until documented progression of disease (up to 4 months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03592641, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2023.

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