Colorectal CancerPhase 1NCT01016860
OSI-906 and Irinotecan in Patients With Advanced Cancer
A Phase 1 study testing OSI-906 and irinotecan in people with Colorectal Cancer, run by University of Colorado, Denver at 1 site in United States.
Trial summary
This study plans to learn more about an investigational drug called OSI-906. OSI-906 is being looked at to see if it could be a treatment for advanced cancer. "The FDA is the U.S. government agency that reviews the results of research of drugs and decides if it can be sold in the U.S. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- OSI-906 and irinotecan
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2009to Apr 2013
- Phase
- Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Dose Escalation Phase: Histological or cytopathological diagnosis of an advanced cancer that is refractory to standard therapy or for which no standard therapy exists.
- Irinotecan must be listed in the Compendia for reimbursement, ie. colorectal cancer; lung cancer; gastric; esophageal, cervical and ovarian cancer.
- Cohort Expansion Phase: Histological or cytopathological diagnosis of advanced colorectal cancer with known Kirsten rat sarcoma (KRAS) mutation status. All patients must have received and progressed or be intolerable of first-line therapy with an oxaliplatin-containing regimen. Patients must be screened using the OSI-906 integrated classifier.
- Cohort 1 (12 patients): Window of opportunity cohort: Patients with a score of at least 4 out of 5 by the OSI-906 integrated classifier who are irinotecan-naive will receive OSI-906 as a single agent until disease progression. Patients must be non surgically resectable or not a surgical candidate because of comorbid conditions. At disease progression, if the patient had a best response of at least stable disease for 3 cycles (9 weeks), irinotecan may be added to OSI-906.
- Cohort 2: (16 patients: 8 KRAS wild-type (WT) and 8 KRAS Mutant(MT). Patients who have score of less than 4 by the OSI-906 integrated classifier will have OSI-906 added to irinotecan on disease progression to irinotecan (patients that are KRAS WT will have received cetuximab with irinotecan). Patients who are treated in the dose escalation phase at the recommended phase II dose of the combination and meet the criteria for Cohort 2 of the expanded phase may be counted towards the dose expansion patient numbers.
- Age ≥18 years old
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- Patients must have an Eastern Co-operative oncology group (ECOG) performance status of 0-1
- Life expectancy of at least three months.
- Adequate hematological function and bone marrow reserve:
- Hematopoetic: Neutrophil count ≥ 1.5 x 109/L (1,500/mm3), Platelet count ≥ 75 x 109/L, Hemoglobin ≥ 9.0g/dL
- Adequate hepatic and renal function Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 fold upper limit of normal (ULN) Bilirubin ≤ 1.5 X ULN Creatinine ≤ 1.5 fold ULN or calculated creatinine clearance, using the Cockcroft-Gault formula > 60 mL/min, if just below 60 mL/min then Glomerular Filtration Rate > 60 mL/min as determined by 24 hour urine collection
- Measurable (according to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria in the dose expansion cohorts or measurable /evaluable disease in the Dose Escalation phase,
- Ability to understand the requirements of the study, provide written informed consent and comply with the study protocol procedures.
- A: Documentation of KRAS status must be performed prior to enrollment.
Who cannot join
- Concurrent symptomatic central nervous system involvement, brain or meningeal metastases
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, uncontrolled diabetes, uncontrollable hypertension or psychiatric illness/social situations that would limit compliance with study requirements
- Documented history of diabetes
- Corrected QT (QTc) interval > 450 msec at baseline
- Drugs with a Risk of Causing corrected QT interval Prolongation: Drugs that have a risk of causing QT interval prolongation are prohibited within 14 days prior to Day 1 dosing and while on study to avoid exacerbation of any OSI-906 potential side effects
- Known positive serology for the human immunodeficiency virus (HIV), Hepatitis B and/or Hepatitis C
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- Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
- Gastrointestinal tract disease (including peptic ulcer disease) or prior surgery resulting in an inability to take oral medications
- Patients may have had prior therapy, providing the following conditions are met:
- Chemotherapy: A minimum of 3 weeks (4 weeks for carboplatin or investigational anticancer agents and 6 weeks for nitrosoureas and mitomycin C) must have elapsed between the end of treatment and start of treatment. Patients must have recovered from any treatment-related toxicities (except for alopecia, fatigue, and grade 1 neurotoxicity) prior to start of treatment.
- Hormonal therapy: Patients may have had prior anticancer hormonal therapy provided it is discontinued prior to start of treatment. However, patients with prostate cancer with evidence of progressive disease may continue on therapy that produces medical castration (eg, goserelin or leuprorelin), provided this therapy was commenced at least 3 months earlier.
- Radiation: Patients may have had prior radiation therapy provided they have recovered from the acute, toxic effects of radiotherapy prior to start of treatment. A minimum of 21 days must have elapsed between the end of radiotherapy and start of treatment if the radiation affected more than 25% of bone marrow otherwise a 14 days wash out is required.
- Surgery: Previous surgery is permitted provided that wound healing has occurred prior to start of treatment.
- Laboratory results: international normalized ratio (INR) ≥ 1.5 X ULN and activated partial thromboplastin time (aPTT) ≥ 1.5 X ULN
- Fasting blood glucose of >125mg/dL at baseline and on Day 1 of dosing.
- Women who are pregnant or breast feeding because of teratogenic potential.
- Women of childbearing potential in whom pregnancy cannot be excluded or who are not using an adequate method of contraception because of teratogenic potential.
- Prior documented hypersensitivity to irinotecan
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Denver
Aurora, Colorado, 80045
About this study
Official title: A Phase I/IB Study of OSI-906 and Irinotecan in Patients With Advanced Cancer With Expanded Cohorts of Patients With Colorectal Cancer Stratified by the OSI-906 Integrated Classifier
This study plans to learn more about an investigational drug called OSI-906. OSI-906 is being looked at to see if it could be a treatment for advanced cancer. "The FDA is the U.S. government agency that reviews the results of research of drugs and decides if it can be sold in the U.S. OSI-906 has been given to over 185 people with cancer.
Read the detailed description
This study plans to learn more about an investigational drug called OSI-906. OSI-906 is being looked at to see if it could be a treatment for advanced cancer.
Subjects will also receive a drug called irinotecan (also called Camptosar®). This drug is FDA approved for the treatment of metastatic colon cancer and some other types of cancer. The study drug and irinotecan have never been tested together in humans. It is unknown if the combination will be safe and/or effective in the treatment of human cancers.
The purpose of this study is to find the answers to the following research questions:
- What is the highest dose of the study drug that can be given to subjects in combination with irinotecan without causing side effects that are too severe?
- How is the combination of the study drug and irinotecan handled in the blood of subjects with advanced cancer? Does either the study drug or irinotecan have an effect on how the other works?
- What are the most common side effects of the study drug and irinotecan when given together to subjects with advanced cancer?
- Is the combination of the study drug and irinotecan effective in stopping the growth or shrinking the size of your tumor?
- Conditions
- Colorectal Cancer
- Being tested
- OSI-906, irinotecan
- Keywords
- OSI-906, irinotecan, 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
Also called Linsitinib
OSI-906 will be given orally in tablets for one dose starting on Cycle 1 Day-3 then on Cycle 1 Day 2-4, 8-10 and 15-17. Cycle is 21 days. Subsequent cycles, dosing will start be Day 1-3, 8-10 and 15-17
irinotecanDrug
Also called Camptosar
Irinotecan will be administered IV over 90 minutes on Day 1 and 8 of a 21-day cycle
| Study group | Role | What they receive |
|---|---|---|
| OSI-906 and/or irinotecan | Experimental | Dose Escalation Phase: Treatment for Cycle 1 will commence on Day -3 of a 21-day cycle (3 weeks) when a single dose OSI-906 is given with full pharmacokinetics(PK) sampling at predetermined time points. Irinotecan will be administered intravenously over 90 minutes on Day 1 and Day 8 with full PK sampling on Day 1. The institution of oral dosing of OSI-906 2-4, 8-10, 15-17 (for cycle 1 only) will be given followed by full PK sampling of both drugs on Day 8. Pre-dose samples of OSI-906 will be drawn on Cycle 1 Days 8, 10, 15, 17 and Cycle 2 Days 1, 8, 10, 15 and 17. For Cycle 2 and thereafter, both drugs will be administered starting on Day 1. Receives: Drug: OSI-906; Drug: irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) and the recommend phase II dose (RP2D) for the combination of irinotecan and OSI-906 in patients with advanced cancer.
Measured: Up to 28 days of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2009 (estimated)
- Study startDec 2009
- Primary completionApr 2013
- Study completionApr 2013
Why it stopped: This study was discontinued due to a shown lack of efficacy in the investigational agent
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stephen Leong, M.D, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01016860
- Sponsor's protocol ID
- 09-0705.cc
- Other IDs
- NCI-2011-03204
- Status last verified
- Oct 2013
- First submitted
- 18 Nov 2009
- Last updated
- 21 Oct 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Davis SL, Eckhardt SG, Diamond JR, Messersmith WA, Dasari A, Weekes CD, Lieu CH, Kane M, Choon Tan A, Pitts TM, Leong S. A Phase I Dose-Escalation Study of Linsitinib (OSI-906), a Small-Molecule Dual Insulin-Like Growth Factor-1 Receptor/Insulin Receptor Kinase Inhibitor, in Combination with Irinotecan in Patients with Advanced Cancer. Oncologist. 2018 Dec;23(12):1409-e140. doi: 10.1634/theoncologist.2018-0315. Epub 2018 Aug 23.
PubMed 30139840
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IB Study of OSI-906 and Irinotecan in Patients With Advanced Cancer With Expanded Cohorts of Patients With Colorectal Cancer Stratified by the OSI-906 Integrated Classifier
- ClinicalTrials.gov ID
- NCT01016860
- Acronym / sponsor ID
- 09-0705.cc
- Conditions
- Colorectal Cancer
- Keywords
- OSI-906, irinotecan, colorectal cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study was discontinued due to a shown lack of efficacy in the investigational agent
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- Dec 2009
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 20 Nov 2009 (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 study plans to learn more about an investigational drug called OSI-906. OSI-906 is being looked at to see if it could be a treatment for advanced cancer. "The FDA is the U.S. government agency that reviews the results of research of drugs and decides if it can be sold in the U.S. OSI-906 has been given to over 185 people with cancer.
Detailed description
This study plans to learn more about an investigational drug called OSI-906. OSI-906 is being looked at to see if it could be a treatment for advanced cancer.
Subjects will also receive a drug called irinotecan (also called Camptosar®). This drug is FDA approved for the treatment of metastatic colon cancer and some other types of cancer. The study drug and irinotecan have never been tested together in humans. It is unknown if the combination will be safe and/or effective in the treatment of human cancers.
The purpose of this study is to find the answers to the following research questions:
- What is the highest dose of the study drug that can be given to subjects in combination with irinotecan without causing side effects that are too severe?
- How is the combination of the study drug and irinotecan handled in the blood of subjects with advanced cancer? Does either the study drug or irinotecan have an effect on how the other works?
- What are the most common side effects of the study drug and irinotecan when given together to subjects with advanced cancer?
- Is the combination of the study drug and irinotecan effective in stopping the growth or shrinking the size of your tumor?
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| OSI-906 and/or irinotecan | Experimental | Drug: OSI-906, Drug: irinotecanDose Escalation Phase: Treatment for Cycle 1 will commence on Day -3 of a 21-day cycle (3 weeks) when a single dose OSI-906 is given with full pharmacokinetics(PK) sampling at predetermined time points. Irinotecan will be administered intravenously over 90 minutes on Day 1 and Day 8 with full PK sampling on Day 1. The institution of oral dosing of OSI-906 2-4, 8-10, 15-17 (for cycle 1 only) will be given followed by full PK sampling of both drugs on Day 8. Pre-dose samples of OSI-906 will be drawn on Cycle 1 Days 8, 10, 15, 17 and Cycle 2 Days 1, 8, 10, 15 and 17. For Cycle 2 and thereafter, both drugs will be administered starting on Day 1. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Dose Escalation Phase: Histological or cytopathological diagnosis of an advanced cancer that is refractory to standard therapy or for which no standard therapy exists.
- Irinotecan must be listed in the Compendia for reimbursement, ie. colorectal cancer; lung cancer; gastric; esophageal, cervical and ovarian cancer.
- Cohort Expansion Phase: Histological or cytopathological diagnosis of advanced colorectal cancer with known Kirsten rat sarcoma (KRAS) mutation status. All patients must have received and progressed or be intolerable of first-line therapy with an oxaliplatin-containing regimen. Patients must be screened using the OSI-906 integrated classifier.
- Cohort 1 (12 patients): Window of opportunity cohort: Patients with a score of at least 4 out of 5 by the OSI-906 integrated classifier who are irinotecan-naive will receive OSI-906 as a single agent until disease progression. Patients must be non surgically resectable or not a surgical candidate because of comorbid conditions. At disease progression, if the patient had a best response of at least stable disease for 3 cycles (9 weeks), irinotecan may be added to OSI-906.
- Cohort 2: (16 patients: 8 KRAS wild-type (WT) and 8 KRAS Mutant(MT). Patients who have score of less than 4 by the OSI-906 integrated classifier will have OSI-906 added to irinotecan on disease progression to irinotecan (patients that are KRAS WT will have received cetuximab with irinotecan). Patients who are treated in the dose escalation phase at the recommended phase II dose of the combination and meet the criteria for Cohort 2 of the expanded phase may be counted towards the dose expansion patient numbers.
Key exclusion criteria (18 listed)
- Concurrent symptomatic central nervous system involvement, brain or meningeal metastases
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, uncontrolled diabetes, uncontrollable hypertension or psychiatric illness/social situations that would limit compliance with study requirements
- Documented history of diabetes
- Corrected QT (QTc) interval > 450 msec at baseline
- Drugs with a Risk of Causing corrected QT interval Prolongation: Drugs that have a risk of causing QT interval prolongation are prohibited within 14 days prior to Day 1 dosing and while on study to avoid exacerbation of any OSI-906 potential side effects
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-906Also: LinsitinibOSI-906 will be given orally in tablets for one dose starting on Cycle 1 Day-3 then on Cycle 1 Day 2-4, 8-10 and 15-17. Cycle is 21 days. Subsequent cycles, dosing will start be Day 1-3, 8-10 and 15-17 | Drug | OSI-906 and/or irinotecan |
| irinotecanAlso: CamptosarIrinotecan will be administered IV over 90 minutes on Day 1 and 8 of a 21-day cycle | Drug | OSI-906 and/or irinotecan |
Primary outcome
Maximum tolerated dose (MTD) and the recommend phase II dose (RP2D) for the combination of irinotecan and OSI-906 in patients with advanced cancer.
Time frame: Up to 28 days of treatment
Results and safety
The study was stopped early (reason given: This study was discontinued due to a shown lack of efficacy in the investigational agent). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2013.
- Derived from this study: PubMed 30139840Davis SL, Eckhardt SG, Diamond JR, Messersmith WA, Dasari A, Weekes CD, Lieu CH, Kane M, Choon Tan A, Pitts TM, Leong S. A Phase I Dose-Escalation Study of Linsitinib (OSI-906), a Small-Molecule Dual Insulin-Like Growth Factor-1 Receptor/Insulin Receptor Kinase Inhibitor, in Combination with Irinotecan in Patients with Advanced Cancer. Oncologist. 2018 Dec;23(12):1409-e140. doi: 10.1634/theoncologist.2018-0315. Epub 2018 Aug 23.
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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.
Stephen Leong, M.D principal investigator
University of Colorado, Denver
1 site 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 irinotecan in people with Colorectal Cancer, run by University of Colorado, Denver at 1 site 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 14 inclusion and 18 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 21 Oct 2013. 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 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?
The study was stopped early (reason given: This study was discontinued due to a shown lack of efficacy in the investigational agent). Results are not available in the source record.
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?
Maximum tolerated dose (MTD) and the recommend phase II dose (RP2D) for the combination of irinotecan and OSI-906 in patients with advanced cancer. (time frame: Up to 28 days of treatment). 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 NCT01016860, 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 21 Oct 2013.