Colorectal Cancer MetastaticPhase 2NCT01892527
Study of Tivantinib (ARQ 197) Plus Cetuximab in EGFR Inhibitor-Resistant MET High Subjects
A Phase 2 study testing Tivantinib (ARQ197) in people with Colorectal Cancer Metastatic and C-met Overexpression, run by Armando Santoro, MD at 1 site in Italy.
Trial summary
This is a single-arm, Simon 2-stage, phase 2 clinical study conducted in subjects with advanced or metastatic colorectal cancer who have previously received ≥ 1 prior line of systemic therapies and are resistant to EGFR inhibitor (cetuximab or panitumumab). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Colorectal Cancer Metastatic, C-met Overexpression
- What is being tested?
- Tivantinib (ARQ197)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteItaly
- Study dates
- Mar 2013to Mar 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Subjects who meet any of the following criteria will be disqualified from entering the study:
- History of malignancy other than CRC, unless there is an exception that the malignancy has been cured and no tumor- specific treatment for the malignancy has been administered within the 3 years prior to initiation of study treatment (subjects with a history of basal cell carcinoma or benign tumor of cervix can be enrolled if diagnosis and treatment occurred < 3 years prior to enrollment).
- Anticipation of need for a major surgical procedure or radiation therapy (RT) during the study.
- Treatment with chemotherapy, radiotherapy, surgery, immunotherapy, biological therapy, or any other investigational anticancer agent within 3 weeks prior to start of study treatment.
- History of cardiac disease: Congestive heart failure defined as Class II to IV per New York Heart Association (NYHA) classification; active coronary artery disease (CAD); Previously diagnosed bradycardia (subjects with asymptomatic bradycardia and hear rate above 50 bpm are allowed) or other cardiac arrhythmia defined as ≥Grade 2 or higher according to NCI CTCAE, version 4.0, or uncontrolled hypertension; myocardial infarction that occurred within 6 months prior to start of study treatment (myocardial infarction that occurred > 6 months prior the start of study treatment is permitted).
- Malabsorption syndrome, chronic diarrhea (lasting > 4 weeks), inflammatory bowel disease, or partial bowel obstruction.
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- Known metastatic brain or meningeal tumors, unless the subject is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of first dose of study treatment, and is clinically stable (no concomitant therapy, including supportive therapy with steroids or anticonvulsant medications) with respect to the tumor at the time of first dose of study treatment.
- Uncontrolled seizure disorder, spinal cord compression, or carcinomatous meningitis.
- Pericardial or pleural effusion (requiring drainage) or pericardial involvement with the tumor. Subjects with minimal pleural effusion may be eligible upon request by Investigator and approval by Sponsor.
- Clinically significant active infection that requires antibiotic therapy.
- Previous administration of any MET inhibitor (including tivantinib) or EGFR inhibitor (except cetuximab or panitumumab).
- Substance abuse or medical, psychological or social conditions that may, in the opinion of the Investigator, interfere with the subject's participation in the clinical trial or evaluation of the clinical trial results.
- Any condition that is unstable or that could jeopardize the safety of the subject and the subject's protocol compliance.
- Inability to swallow oral medications.
- Pregnant or nursing females.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single-Arm Phase II Study of Tivantinib (ARQ 197) Plus Cetuximab in EGFR Inhibitor-Resistant MET High Subjects With Locally Advanced or Metastatic Colorectal Cancer With Wild-Type KRAS
This is a single-arm, Simon 2-stage, phase 2 clinical study conducted in subjects with advanced or metastatic colorectal cancer who have previously received ≥ 1 prior line of systemic therapies and are resistant to EGFR inhibitor (cetuximab or panitumumab).
This trial will be conducted to determine objective response rate (ORR), progression-free survival (PFS) and overall-survival (OS) of cetuximab plus tivantinib in patients with wild-type KRAS CRC that is resistant to anti-EGFR antibody treatment (cetuximab or panitumumab) and shows overexpression of cMET.
Read the detailed description
This is a single-arm, Simon 2-stage, phase 2 clinical study conducted in subjects with advanced or metastatic colorectal cancer who have received ≥1 prior line of systemic therapies and are resistant to EGFR inhibitor (cetuximab or panitumumab). Fresh tumor tissue is needed for the MET testing, thus a biopsy will be required to participate in this trial. In a minor percentage of subjects archival tumor tissue could be acceptable for this analysis.Eligible subjects will be treated with tivantinib (ARQ 197) at a dose of 360 mg twice daily (a total daily dose of 720 mg) orally in a continuous manner and cetuximab (Erbitux) at a dose of 500 mg/mq i.v. every 2 weeks. The overall treatment period will be divided into continuous 28 days cycles without treatment interruption. Disease status and tumor response will be assessed per modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 at screening (within 4 weeks before the first scheduled dose of study drug), in 8 weeks intervals while the subjects are on treatment or as clinically indicated until progression of disease, withdrawal of consent, death, or lost to follow-up. Tumor measurement will also be performed during the end of treatment visit if not done within the previous 8 weeks. Subjects with progressive disease at any time during the treatment period will discontinue study treatment. Subjects with stable disease (SD), complete response (CR) and partial response (PR) will stay on treatment until disease progression and/or unacceptable toxicity and/or withdrawal of consent is documented. CR and PR must be confirmed no sooner than 4 weeks after the initial observation. After discontinuation from study treatment during the follow-up period, survival status will be obtained by phone every 3 months until the subject dies, withdraws consent from study, or is lost to follow-up, for a maximum of 12 months.
- Conditions
- Colorectal Cancer Metastatic, C-met Overexpression
- Being tested
- Tivantinib (ARQ197)
- Keywords
- Colorectal Cancer Metastatic, wild type KRAS, C-met overexpression, Tivantinib, Cetuximab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tivantinib (ARQ197)Drug
Also called Cetuximab
Eligible subjects will be treated with tivantinib (ARQ 197) at a dose of 360 mg twice daily (a total daily dose of 720 mg) orally in a continuous manner and cetuximab (Erbitux) at a dose of 500 mg/mq i.v. every 2 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Tivantinib plus Cetuximab | Experimental | Single arm Receives: Drug: Tivantinib (ARQ197) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Study of Tivantinib (ARQ 197) plus Cetuximab in EGFR inhibitor-Resistant MET High Subjects with Locally Advanced or Metastatic Colorectal Cancer with Wild-Type KRAS
To determine objective response rate (ORR).
Measured: 36 months
Secondary outcomes (1)
Tivantinib (ARQ 197) plus Cetuximab in EGFR inhibitor-Resistant MET High Subjects
To estimate progression-free survival (PFS).
Measured: 36months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jul 2013 (estimated)
- Study startMar 2013
- Primary completionMay 2016
- Study completionMar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Cancer MetastaticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Armando Santoro, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Armando Santoro, MD, Istituto Clinico Humanitas
- Investigators
- Lorenza Rimassa, MD, Study chair, Istituto Clinico Humanitas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01892527
- Sponsor's protocol ID
- ONC-2012-001
- Status last verified
- Sep 2022
- First submitted
- 6 May 2013
- Last updated
- 9 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-Arm Phase II Study of Tivantinib (ARQ 197) Plus Cetuximab in EGFR Inhibitor-Resistant MET High Subjects With Locally Advanced or Metastatic Colorectal Cancer With Wild-Type KRAS
- ClinicalTrials.gov ID
- NCT01892527
- Acronym / sponsor ID
- ONC-2012-001
- Conditions
- Colorectal Cancer Metastatic, C-met Overexpression
- Keywords
- Colorectal Cancer Metastatic, wild type KRAS, C-met overexpression, Tivantinib, Cetuximab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Armando Santoro, MDUniversity, hospital or other
- Study start
- Mar 2013
- Primary completion
- May 2016 (actual)
- Study completion
- Mar 2017 (actual)
- First posted
- 4 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-arm, Simon 2-stage, phase 2 clinical study conducted in subjects with advanced or metastatic colorectal cancer who have previously received ≥ 1 prior line of systemic therapies and are resistant to EGFR inhibitor (cetuximab or panitumumab).
This trial will be conducted to determine objective response rate (ORR), progression-free survival (PFS) and overall-survival (OS) of cetuximab plus tivantinib in patients with wild-type KRAS CRC that is resistant to anti-EGFR antibody treatment (cetuximab or panitumumab) and shows overexpression of cMET.
Detailed description
This is a single-arm, Simon 2-stage, phase 2 clinical study conducted in subjects with advanced or metastatic colorectal cancer who have received ≥1 prior line of systemic therapies and are resistant to EGFR inhibitor (cetuximab or panitumumab). Fresh tumor tissue is needed for the MET testing, thus a biopsy will be required to participate in this trial. In a minor percentage of subjects archival tumor tissue could be acceptable for this analysis.Eligible subjects will be treated with tivantinib (ARQ 197) at a dose of 360 mg twice daily (a total daily dose of 720 mg) orally in a continuous manner and cetuximab (Erbitux) at a dose of 500 mg/mq i.v. every 2 weeks. The overall treatment period will be divided into continuous 28 days cycles without treatment interruption. Disease status and tumor response will be assessed per modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 at screening (within 4 weeks before the first scheduled dose of study drug), in 8 weeks intervals while the subjects are on treatment or as clinically indicated until progression of disease, withdrawal of consent, death, or lost to follow-up. Tumor measurement will also be performed during the end of treatment visit if not done within the previous 8 weeks. Subjects with progressive disease at any time during the treatment period will discontinue study treatment. Subjects with stable disease (SD), complete response (CR) and partial response (PR) will stay on treatment until disease progression and/or unacceptable toxicity and/or withdrawal of consent is documented. CR and PR must be confirmed no sooner than 4 weeks after the initial observation. After discontinuation from study treatment during the follow-up period, survival status will be obtained by phone every 3 months until the subject dies, withdraws consent from study, or is lost to follow-up, for a maximum of 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tivantinib plus Cetuximab | Experimental | Drug: Tivantinib (ARQ197)Single arm |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (15 listed)
- Subjects who meet any of the following criteria will be disqualified from entering the study:
- History of malignancy other than CRC, unless there is an exception that the malignancy has been cured and no tumor- specific treatment for the malignancy has been administered within the 3 years prior to initiation of study treatment (subjects with a history of basal cell carcinoma or benign tumor of cervix can be enrolled if diagnosis and treatment occurred < 3 years prior to enrollment).
- Anticipation of need for a major surgical procedure or radiation therapy (RT) during the study.
- Treatment with chemotherapy, radiotherapy, surgery, immunotherapy, biological therapy, or any other investigational anticancer agent within 3 weeks prior to start of study treatment.
- History of cardiac disease: Congestive heart failure defined as Class II to IV per New York Heart Association (NYHA) classification; active coronary artery disease (CAD); Previously diagnosed bradycardia (subjects with asymptomatic bradycardia and hear rate above 50 bpm are allowed) or other cardiac arrhythmia defined as ≥Grade 2 or higher according to NCI CTCAE, version 4.0, or uncontrolled hypertension; myocardial infarction that occurred within 6 months prior to start of study treatment (myocardial infarction that occurred > 6 months prior the start of study treatment is permitted).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tivantinib (ARQ197)Also: CetuximabEligible subjects will be treated with tivantinib (ARQ 197) at a dose of 360 mg twice daily (a total daily dose of 720 mg) orally in a continuous manner and cetuximab (Erbitux) at a dose of 500 mg/mq i.v. every 2 weeks. | Drug | Tivantinib plus Cetuximab |
Primary outcome
Study of Tivantinib (ARQ 197) plus Cetuximab in EGFR inhibitor-Resistant MET High Subjects with Locally Advanced or Metastatic Colorectal Cancer with Wild-Type KRAS
Time frame: 36 months
To determine objective response rate (ORR).
1 secondary outcome
Tivantinib (ARQ 197) plus Cetuximab in EGFR inhibitor-Resistant MET High Subjects
Time frame: 36months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lorenza Rimassa, MD study chair
Istituto Clinico Humanitas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tivantinib (ARQ197) in people with Colorectal Cancer Metastatic and C-met Overexpression, run by Armando Santoro, MD at 1 site in Italy.
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 0 inclusion and 15 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: finished, as of the sponsor's last update on 9 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Study of Tivantinib (ARQ 197) plus Cetuximab in EGFR inhibitor-Resistant MET High Subjects with Locally Advanced or Metastatic Colorectal Cancer with Wild-Type KRAS (time frame: 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Sep 2022.