NCT01154335

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
18

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Jul 2010

Typical duration for phase_1

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 29, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 30, 2010

Completed
1 day until next milestone

Study Start

First participant enrolled

July 1, 2010

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2013

Completed
1.7 years until next milestone

Results Posted

Study results publicly available

January 14, 2015

Completed
Last Updated

May 3, 2022

Status Verified

April 1, 2022

Enrollment Period

2.8 years

First QC Date

June 29, 2010

Results QC Date

January 6, 2015

Last Update Submit

April 5, 2022

Conditions

Metastatic Colorectal Cancer

Keywords

refractory metastatic colorectal cancer

Outcome Measures

Primary Outcomes (1)

  • 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

    18 Months

Secondary Outcomes (3)

  • Progression-Free Survival (PFS)

    18 Months

  • Overall Survival (OS)

    18 months

  • Response Rate

    18 months

Study Arms (3)

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

Drug: OSI-906Drug: 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

Drug: OSI-906Drug: 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

Drug: OSI-906Drug: Everolimus

Interventions

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

Dose Level 1Dose Level 2Dose Level 2a
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

Dose Level 1Dose Level 2Dose Level 2a

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • 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

You may not qualify if:

  • 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
  • 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
  • +14 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Florida Cancer Specialists

Fort Myers, Florida, 33916, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Related Publications (1)

  • 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.

    PMID: 25335932DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

3-(8-amino-1-(2-phenylquinolin-7-yl)imidazo(1,5-a)pyrazin-3-yl)-1-methylcyclobutanolEverolimus

Condition Hierarchy (Ancestors)

Intestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

SirolimusMacrolidesLactonesOrganic Chemicals

Results Point of Contact

Title
John D Hainsworth, MD
Organization
Sarah Cannon Research Institute
asksarah@scresearch.net
1-877-691-7274

Study Officials

  • Johanna Bendell, MD

    SCRI Development Innovations, LLC

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 29, 2010

First Posted

June 30, 2010

Study Start

July 1, 2010

Primary Completion

May 1, 2013

Study Completion

May 1, 2013

Last Updated

May 3, 2022

Results First Posted

January 14, 2015

Record last verified: 2022-04

Locations

US(2)