Metastatic Colorectal CancerPhase 1NCT01154335
Everolimus and OSI-906 for Patients With Refractory Metastatic Colorectal Cancer
A Phase 1 study testing OSI-906 and Everolimus in people with Metastatic Colorectal Cancer, run by SCRI Development Innovations, LLC at 2 sites in United States.
Trial summary
The purpose of this study is to determine the maximum tolerated dose (MTD) of the combination of OSI-906 and everolimus for the treatment of patients with refractory metastatic colorectal cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- OSI-906 and Everolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2010to May 2013
- Phase
- Phase 1
- 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
- Metastatic cancer of the colon or rectum that has progressed on or for which the patient is intolerant to or not a candidate for: fluoropyrimidines, oxaliplatin, irinotecan, bevacizumab, and cetuximab or panitumumab.
- Testing for Kras mutation performed;Patients with mutated or wild type Kras are eligible.
- ECOG PS of 0-1
- Life expectancy of ≥ 3 months
- Adequate hematological function with ANC 1500, Platelets of 100,000, and hemoglobin of 9.0
- AST, ALT and Alk. Phos. ≤2.5 x ULN or ≤5 x ULN if known hepatic metastases and a total bilirubin ≤1.5 ULN
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- Serum creatinine of ≤1.5 x ULN
- Fasting blood glucose <150 mg/dL
- Measurable disease according to RECIST 1.1
- Able to swallow whole pills
- INR ≤1.5 - Anticoagulation is allowed with LMW heparin
- Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤2.5 x ULN;If these thresholds are exceeded, the patient can be included after initiation of lipid lowering medication
Who cannot join
- Patients who have received any cancer therapies <4 weeks or 5 half lives (whichever is shorter) of initiating study therapy
- Treatment with any investigational drug ≤ 4 weeks, or 5 half-lives of the drug, whichever is shorter
- Patients who require coumadin for anticoagulation
- Patients who have had major surgery or significant traumatic injury ≤4 weeks of the of study treatment
- Minor surgery (with the exception of port placement) must be completed ≤ 7days prior to study therapy
- Previous treatment with an IGFR inhibitor or MTOR Inhibitor
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- Chronic, systemic treatment with corticosteroids or another immunosuppressive agent
- Patients with QTc interval >450ms
- Patients who require drugs that can prolong QTc.
- Patients with congenital long QT syndrome, history of ventricular tachycardia, or ventricular fibrillation, or Torsades de Pointes with bradycardia.
- Immunization with attenuated live vaccines within 1 week of beginning study therapy or during study period;Close contact to anyone that has received live virus vaccine should be avoided
- Meningeal or brain metastasis
- Other malignancies < 3 years, with the exception of adequately treated basal or squamous cell carcinomas of the skin, or carcinoma in situ of the cervix
- Patients with known HIV
- Patients with positive testing for hepatitis B or C
- Patients with risk factors for hepatitis must be tested for hepatitis viral loadHepatitis risk factors include the following:
- Lived in Asia, Africa, Central and South America, Eastern Europe, Spain, Portugal, and Greece Any blood transfusions before 1990 Any IV drug use Any dialysis Household contact with a Hep B infected patient Mother had Hep B High-risk sexual activity Body piercing/tattoos
- History suggestive of hepatitis B
- Any severe or uncontrolled conditions that could affect their study participation such as:Severely impaired lung function;DCLO ≤ 50% of normal predicted value;O² Sat <88% at rest on room air
- Congestive Heart Failure of NYHA Class III or IV
- Unstable angina, symptomatic CHF, MI ≤ 6 months, serious uncontrolled cardiac arrhythmia or any other clinically significant heart disease
- CVA, TIA, angioplasty, or cardiac stenting <12 months
- Ventricular arrhythmia requiring medication
- Known history of diabetes and/or patients who require ongoing use of insulin or oral anti-hyperglycemic therapy
- Known liver disease
- Impairment of GI function or gastrointestinal disease that in may significantly alter the absorption of study drugs
- Concurrent treatment with drugs that are strong CYP3A4 inducers or moderate/strong CYP3A4 inhibitors
- Concurrent treatment with drugs that are strong CYP1A2 inhibitors or inducers Women who are pregnant or breastfeeding.
- Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Florida Cancer Specialists
Fort Myers, Florida, 33916
Tennessee Oncology
Nashville, Tennessee, 37203
About this study
Official title: A Phase I Study of Everolimus (mTOR Inhibitor) and OSI-906 (Dual IGFR and IR Tyrosine Kinase Inhibitor) for the Treatment of Patients With Refractory Metastatic Colorectal Cancer
The purpose of this study is to determine the maximum tolerated dose (MTD) of the combination of OSI-906 and everolimus for the treatment of patients with refractory metastatic colorectal cancer.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- OSI-906, Everolimus
- Keywords
- refractory metastatic colorectal cancer
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OSI-906Drug
Dose Level 1: 50 mg Twice a Day, cycle-28 days Dose Level 2: 100 mg Twice a Day, cycle-28 days Dose Level 2a: 100 mg Twice a Day, cycle-28 days
EverolimusDrug
Dose Level 1: 5mg Daily, cycle-28 days Dose Level 2: 10mg Daily, cycle-28 days Dose Level 2a: 5mg Daily, cycle-28 days
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 1 | Experimental | combination of OSI-906 and everolimus
OSI-906: 50 mg Twice a Day, cycle-28 days
Everolimus: 5mg Daily, cycle-28 days Receives: Drug: OSI-906; Drug: Everolimus |
| Dose Level 2 | Experimental | combination of OSI-906 and everolimus
OSI-906: 100 mg Twice a Day, cycle-28 days
Everolimus: 10mg Daily, cycle-28 days Receives: Drug: OSI-906; Drug: Everolimus |
| Dose Level 2a | Experimental | combination of OSI-906 and everolimus
OSI-906: 100 mg Twice a Day, cycle-28 days
Everolimus: 5mg Daily, cycle-28 days Receives: Drug: OSI-906; Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
To Determine the Maximum Tolerated Dose (MTD) of the Combination of OSI-906 and Everolimus for the Treatment of Patients With Refractory Metastatic Colorectal Cancer.
The MTD of the drug combination will be determined as the highest dose at which ≤1 of 6 subjects experiences a Grade 3 or Grade 4 DLT according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0
Measured: 18 Months
Secondary outcomes (3)
Progression-Free Survival (PFS)
Progression-free survival (PFS) is defined as the time between Day 1 Cycle 1 and date of first documented recurrence or death. Patients who do not exhibit progression while on trial will be censored at their last known assessment. Progression is defined per RECIST criteria as either 1) at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest (nadir) sum since the treatment started, or the appearance of one or more new lesions. Requires not only 20% increase, but absolute increase of a minimum of 5 mm over sum. OR 2) Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Measured: 18 Months
Overall Survival (OS)
Overall survival (OS) is defined as the time between Day 1 Cycle 1 to the date of death from any cause. Those remaining alive will be censored at their last known assessment or follow-up.
Measured: 18 months
Response Rate
Response rate (RR) will be estimated as the proportion of patients exhibiting complete response or partial response out of all evaluable cases. Complete Response is defined per RECIST as disappearance of all target/non-target lesions and normalization of tumor markers. Partial Response is defined per RECIST as At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2010 (estimated)
- Study startJul 2010
- Primary completionMay 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Colorectal CancerStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- SCRI Development Innovations, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals, OSI Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Johanna Bendell, MD, Study chair, SCRI Development Innovations, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01154335
- Sponsor's protocol ID
- SCRI GI 124
- Status last verified
- Apr 2022
- First submitted
- 29 Jun 2010
- Last updated
- 3 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Bendell JC, Jones SF, Hart L, Spigel DR, Lane CM, Earwood C, Infante JR, Barton J, Burris HA. A phase Ib study of linsitinib (OSI-906), a dual inhibitor of IGF-1R and IR tyrosine kinase, in combination with everolimus as treatment for patients with refractory metastatic colorectal cancer. Invest New Drugs. 2015 Feb;33(1):187-93. doi: 10.1007/s10637-014-0177-3. Epub 2014 Oct 22.
PubMed 25335932
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Everolimus (mTOR Inhibitor) and OSI-906 (Dual IGFR and IR Tyrosine Kinase Inhibitor) for the Treatment of Patients With Refractory Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT01154335
- Acronym / sponsor ID
- SCRI GI 124
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- refractory metastatic colorectal cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- SCRI Development Innovations, LLCUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals, OSI Pharmaceuticals
- Study start
- Jul 2010
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 30 Jun 2010 (estimated)
- Results
- Posted 14 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the maximum tolerated dose (MTD) of the combination of OSI-906 and everolimus for the treatment of patients with refractory metastatic colorectal cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose Level 1 | Experimental | Drug: OSI-906, Drug: Everolimuscombination of OSI-906 and everolimus OSI-906: 50 mg Twice a Day, cycle-28 days Everolimus: 5mg Daily, cycle-28 days |
| Dose Level 2 | Experimental | Drug: OSI-906, Drug: Everolimuscombination of OSI-906 and everolimus OSI-906: 100 mg Twice a Day, cycle-28 days Everolimus: 10mg Daily, cycle-28 days |
| Dose Level 2a | Experimental | Drug: OSI-906, Drug: Everolimuscombination of OSI-906 and everolimus OSI-906: 100 mg Twice a Day, cycle-28 days Everolimus: 5mg Daily, cycle-28 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Metastatic cancer of the colon or rectum that has progressed on or for which the patient is intolerant to or not a candidate for: fluoropyrimidines, oxaliplatin, irinotecan, bevacizumab, and cetuximab or panitumumab.
- Testing for Kras mutation performed;Patients with mutated or wild type Kras are eligible.
- ECOG PS of 0-1
- Life expectancy of ≥ 3 months
- Adequate hematological function with ANC 1500, Platelets of 100,000, and hemoglobin of 9.0
Key exclusion criteria (29 listed)
- Patients who have received any cancer therapies <4 weeks or 5 half lives (whichever is shorter) of initiating study therapy
- Treatment with any investigational drug ≤ 4 weeks, or 5 half-lives of the drug, whichever is shorter
- Patients who require coumadin for anticoagulation
- Patients who have had major surgery or significant traumatic injury ≤4 weeks of the of study treatment
- Minor surgery (with the exception of port placement) must be completed ≤ 7days prior to study therapy
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 |
|---|---|---|
| OSI-906Dose Level 1: 50 mg Twice a Day, cycle-28 days Dose Level 2: 100 mg Twice a Day, cycle-28 days Dose Level 2a: 100 mg Twice a Day, cycle-28 days | Drug | Dose Level 1, Dose Level 2, Dose Level 2a |
| EverolimusDose Level 1: 5mg Daily, cycle-28 days Dose Level 2: 10mg Daily, cycle-28 days Dose Level 2a: 5mg Daily, cycle-28 days | Drug | Dose Level 1, Dose Level 2, Dose Level 2a |
Primary outcome
To Determine the Maximum Tolerated Dose (MTD) of the Combination of OSI-906 and Everolimus for the Treatment of Patients With Refractory Metastatic Colorectal Cancer.
Time frame: 18 Months
The MTD of the drug combination will be determined as the highest dose at which ≤1 of 6 subjects experiences a Grade 3 or Grade 4 DLT according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0
3 secondary outcomes
Progression-Free Survival (PFS)
Time frame: 18 Months
Overall Survival (OS)
Time frame: 18 months
Response Rate
Time frame: 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25335932Bendell JC, Jones SF, Hart L, Spigel DR, Lane CM, Earwood C, Infante JR, Barton J, Burris HA. A phase Ib study of linsitinib (OSI-906), a dual inhibitor of IGF-1R and IR tyrosine kinase, in combination with everolimus as treatment for patients with refractory metastatic colorectal cancer. Invest New Drugs. 2015 Feb;33(1):187-93. doi: 10.1007/s10637-014-0177-3. Epub 2014 Oct 22.
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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.
Johanna Bendell, MD study chair
SCRI Development Innovations, LLC
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing OSI-906 and Everolimus in people with Metastatic Colorectal Cancer, run by SCRI Development Innovations, LLC at 2 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 12 inclusion and 29 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 3 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 14 Jan 2015). 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?
To Determine the Maximum Tolerated Dose (MTD) of the Combination of OSI-906 and Everolimus for the Treatment of Patients With Refractory Metastatic Colorectal Cancer. (time frame: 18 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 NCT01154335, 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 3 May 2022.