Colorectal CancerPhase 1/2NCT00522665
Phase I/Randomized Phase II Study of Second Line Therapy With Irinotecan + Cetuximab +/- RAD001 for Colorectal Cancer
A Phase 1/2 study testing Irinotecan, Cetuximab and RAD001 in people with Colorectal Cancer, run by Hoosier Cancer Research Network at 14 sites in United States.
Trial summary
The addition of RAD001, an mTOR inhibitor, to irinotecan and anti-EGFR antibody cetuximab may increase efficacy for patients with metastatic colorectal cancer who progressed on prior chemotherapy. 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?
- Irinotecan, Cetuximab and RAD001
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 14 sitesUnited States
- Study dates
- Aug 2007to Feb 2015
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histological or cytological proof of colon or rectal adenocarcinoma
- Measurable site of disease according to RECIST that has not been previously irradiated
- Must have metastatic colorectal cancer which progressed after first line chemotherapy +/- bevacizumab
- Blood sample collected within 21 days prior to being registered for protocol therapy for UTG1A1 genotype analysis. (Patients with the UGT1A1 *28 7/7 genotype (homozygosity for the TA7 allele) will be excluded from the Phase I stage of the study. During the Phase II stage of the study, subjects will be allowed to participate but must begin treatment at dose level -1 of irinotecan.)
- A history of other malignancies (non-colorectal) is allowed, provided it has been curatively treated and demonstrates no evidence for recurrence of that cancer
- Prior radiation therapy allowed to < 25% of the bone marrow
Show all 10Show fewer
- Age ≥ 18 years at the time of consent
- Written informed consent and HIPAA authorization for release of personal health information
- Females of childbearing potential and males must be willing to use an effective method of contraception
- Females of childbearing potential must have a negative pregnancy test within 7 days of being registered for protocol therapy
Who cannot join
- No more than one prior chemotherapy regimen for metastatic colorectal cancer, at least 28 days prior to being registered for protocol therapy
- No prior treatment with cetuximab
- No prior treatment with an mTOR inhibitor
- No known hypersensitivity to cetuximab, RAD001 (everolimus), other rapamycins (sirolimus, temsirolimus) or to its excipients
- No treatment with any investigational agent within 28 days prior to being registered for protocol therapy
- No symptomatic brain metastasis
Show all 17Show fewer
- No uncontrolled diabetes as defined by a fasting serum glucose >1.5 x ULN
- No chronic treatment with systemic steroids or another immuno-suppressive agent
- No serious non-healing wound, ulcer, bone fracture, major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to being registered for protocol therapy
- No liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
- No active bleeding or a pathological condition that is associated with a high risk of bleeding
- No uncontrolled systemic disease including active infections or uncontrolled hypertension
- No known history of HIV seropositivity
- No impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
- No nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with protocol therapy
- No planned immunization with attenuated live viruses during the study period
- Females must not be breastfeeding
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
Cancer Care Center of Southern Indiana
Bloomington, Indiana, 47403
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
Oncology Hematology Associates of SW Indiana
Evansville, Indiana, 47714
Medical & Surgical Specialists, LLC
Galesburg, Illinois, 61401
IN Onc/Hem Associates
Indianapolis, Indiana, 46202
Indiana University Simon Cancer Center
Indianapolis, Indiana, 46202
St. Vincent Hospital & Health Centers
Indianapolis, Indiana, 46206
Community Regional Cancer Center
Indianapolis, Indiana, 46256
Arnett Cancer Care
Lafayette, Indiana, 47904
Horizon Oncology Center
Lafayette, Indiana, 47905
Monroe Medical Associates
Munster, Indiana, 46321
Center for Cancer Care, Inc., P.C.
New Albany, Indiana, 47150
Northern Indiana Cancer Research Consortium
South Bend, Indiana, 46601
Siteman Cancer Center
St Louis, Missouri, 63110
About this study
Official title: Phase I / Randomized Phase II Study of Second Line Therapy With Irinotecan and Cetuximab With or Without RAD001, an Oral mTOR Inhibitor for Patients With Metastatic Colorectal Cancer: Hoosier Oncology Group GI05-102
The addition of RAD001, an mTOR inhibitor, to irinotecan and anti-EGFR antibody cetuximab may increase efficacy for patients with metastatic colorectal cancer who progressed on prior chemotherapy. This approach is biologically directed to overall target the cancer cell at multiple levels, and potentially preventing chemotherapy and EGFR-therapy resistance.
Read the detailed description
OUTLINE: This is a multi-center study.
PHASE I:
- UGT1A1 *28 7/7 genotype IS NOT present
- Cetuximab 250 mg/m2 IV days 1, 8, and 15
- Irinotecan 125 mg/m2 IV days 1 and 8
- RAD001 PO QD (dose determined at the time of registration; subjects will remain at this dose level until treatment discontinuation)
PHASE II:
- Randomization based on UGT1A1 *28 7/7 Genotype or Prior Irinotecan Exposure
ARM A:
- Cetuximab 250 mg/m2 IV days 1, 8, and 15
- Irinotecan 125 mg/m2 IV days 1 and 8
AT TIME OF PROGRESSIVE DISEASE, ARM A TREATMENT WILL CROSSOVER:
- Cetuximab 250 mg/m2 IV days 1, 8, and 15
- Irinotecan 125 mg/m2 IV days 1 and 8
- RAD001 PO QD (maximum tolerated dose)
ARM B:
- Cetuximab 250 mg/m2 IV days 1, 8, and 15
- Irinotecan 125 mg/m2 IV days 1 and 8
- RAD001 PO QD (maximum tolerated dose)
AT TIME OF PROGRESSIVE DISEASE, ARM B TREATMENT WILL BE DISCONTINUED
ECOG performance status 0-2
Life Expectancy: Not specified
Hematopoietic:
- Absolute neutrophil count (ANC) ≥ 1,500 mm3
- Platelets ≥ 100,000 mm3
- Hemoglobin (Hgb) ≥ 9 g/dL
- White blood cell count (WBC) ≥ 2,000 mm3
- INR < 1.5 x upper limit of normal (ULN) if not on anticoagulation (if on anticoagulation must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin)
- PTT < 1.5 x ULN
Hepatic:
- Bilirubin ≤ 1.5 x ULN
- Aspartate aminotransferase (AST, SGOT) ≤ 2.5 x ULN
- Alanine aminotransferase (ALT, SGPT) ≤ 2.5 x ULN
- Albumin ≥ 3.0 g/dL
Renal:
- Calculated creatinine clearance of ≥ 60 cc/min using the Cockcroft-Gault formula
Cardiovascular:
- No uncontrolled cardiac arrhythmia requiring medication, transient ischemic attack (TIA), or cerebrovascular accident (CVA) within 6 months prior to being registered for protocol therapy
- No uncontrolled congestive heart failure, myocardial infarction, or unstable angina within 6 months prior to being registered for protocol therapy
Pulmonary:
- No severely impaired lung function as demonstrated by pulse O2 saturation ≤ 90% at rest on room air, or pulmonary function test FEV1 ≤ 2L
- No history of prior chronic lung infection such as tuberculosis, atypical tuberculosis, or histoplasmosis as evidenced by a chest CT or x-ray within 21 days prior to being registered for protocol therapy
- Conditions
- Colorectal Cancer
- Being tested
- Irinotecan, Cetuximab, RAD001
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IrinotecanDrug
Irinotecan 125 mg/m2 IV days 1 and 8
CetuximabBiological
Cetuximab 250mg/m2 IV days 1, 8 and 15
RAD001Biological
Patients on Arm A will crossover and receive RAD001 at disease progression
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Irinotecan + Cetuximab +/- RAD001 | Active comparator | Not described Receives: Drug: Irinotecan; Biological: Cetuximab; Biological: RAD001 |
| Arm B: Ironotecan + Cetuximab | Active comparator | Not described Receives: Drug: Irinotecan; Biological: Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the MTD of RAD001 in combination with irinotecan and cetuximab as second line therapy in patients with metastatic colorectal cancer
Measured: Phase I
To evaluate the objective response (CR or PR) rates of patients treated with irinotecan and cetuximab with or without RAD001 in patients with metastatic colorectal cancer
Measured: Phase II
Secondary outcomes (2)
To evaluate the pharmacokinetic (PK) profile for RAD001 after one cycle of therapy, on cycle 2 day 1
Measured: Phase I
To evaluate the time to progression, duration of objective response (CR or PR) and overall survival of patients treated with irinotecan and cetuximab with or without RAD001
Measured: Phase II
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2007 (estimated)
- Study startAug 2007
- Primary completionMay 2011
- Study completionFeb 2015
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.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoosier Cancer Research Network
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals, Pfizer
- Responsible party
- Sponsor
- Investigators
- Gabriela Chiorean, M.D., Study chair, Hoosier Oncology Group, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00522665
- Sponsor's protocol ID
- GI05-102
- Status last verified
- May 2015
- First submitted
- 28 Aug 2007
- Last updated
- 15 May 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Chiorean EG, Picus J, Breen T, Ansari RH, Harb WA, Burns M, Spittler AJ, Loehrer PJ. Phase I/II study of everolimus (E) with irinotecan (Iri) and cetuximab (C) in 2nd line metastatic colorectal cancer (mCRC): Hoosier Cancer Research Network GI05-102. J Clin Oncol 33:5s, 2015 (suppl; abstr 3618)
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I / Randomized Phase II Study of Second Line Therapy With Irinotecan and Cetuximab With or Without RAD001, an Oral mTOR Inhibitor for Patients With Metastatic Colorectal Cancer: Hoosier Oncology Group GI05-102
- ClinicalTrials.gov ID
- NCT00522665
- Acronym / sponsor ID
- GI05-102
- Conditions
- Colorectal Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Hoosier Cancer Research NetworkUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals, Pfizer
- Study start
- Aug 2007
- Primary completion
- May 2011 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 30 Aug 2007 (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.
The addition of RAD001, an mTOR inhibitor, to irinotecan and anti-EGFR antibody cetuximab may increase efficacy for patients with metastatic colorectal cancer who progressed on prior chemotherapy. This approach is biologically directed to overall target the cancer cell at multiple levels, and potentially preventing chemotherapy and EGFR-therapy resistance.
Detailed description
OUTLINE: This is a multi-center study.
PHASE I:
- UGT1A1 *28 7/7 genotype IS NOT present
- Cetuximab 250 mg/m2 IV days 1, 8, and 15
- Irinotecan 125 mg/m2 IV days 1 and 8
- RAD001 PO QD (dose determined at the time of registration; subjects will remain at this dose level until treatment discontinuation)
PHASE II:
- Randomization based on UGT1A1 *28 7/7 Genotype or Prior Irinotecan Exposure
ARM A:
- Cetuximab 250 mg/m2 IV days 1, 8, and 15
- Irinotecan 125 mg/m2 IV days 1 and 8
AT TIME OF PROGRESSIVE DISEASE, ARM A TREATMENT WILL CROSSOVER:
- Cetuximab 250 mg/m2 IV days 1, 8, and 15
- Irinotecan 125 mg/m2 IV days 1 and 8
- RAD001 PO QD (maximum tolerated dose)
ARM B:
- Cetuximab 250 mg/m2 IV days 1, 8, and 15
- Irinotecan 125 mg/m2 IV days 1 and 8
- RAD001 PO QD (maximum tolerated dose)
AT TIME OF PROGRESSIVE DISEASE, ARM B TREATMENT WILL BE DISCONTINUED
ECOG performance status 0-2
Life Expectancy: Not specified
Hematopoietic:
- Absolute neutrophil count (ANC) ≥ 1,500 mm3
- Platelets ≥ 100,000 mm3
- Hemoglobin (Hgb) ≥ 9 g/dL
- White blood cell count (WBC) ≥ 2,000 mm3
- INR < 1.5 x upper limit of normal (ULN) if not on anticoagulation (if on anticoagulation must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin)
- PTT < 1.5 x ULN
Hepatic:
- Bilirubin ≤ 1.5 x ULN
- Aspartate aminotransferase (AST, SGOT) ≤ 2.5 x ULN
- Alanine aminotransferase (ALT, SGPT) ≤ 2.5 x ULN
- Albumin ≥ 3.0 g/dL
Renal:
- Calculated creatinine clearance of ≥ 60 cc/min using the Cockcroft-Gault formula
Cardiovascular:
- No uncontrolled cardiac arrhythmia requiring medication, transient ischemic attack (TIA), or cerebrovascular accident (CVA) within 6 months prior to being registered for protocol therapy
- No uncontrolled congestive heart failure, myocardial infarction, or unstable angina within 6 months prior to being registered for protocol therapy
Pulmonary:
- No severely impaired lung function as demonstrated by pulse O2 saturation ≤ 90% at rest on room air, or pulmonary function test FEV1 ≤ 2L
- No history of prior chronic lung infection such as tuberculosis, atypical tuberculosis, or histoplasmosis as evidenced by a chest CT or x-ray within 21 days prior to being registered for protocol therapy
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: Irinotecan + Cetuximab +/- RAD001 | Active comparator | Drug: Irinotecan, Biological: Cetuximab, Biological: RAD001 |
| Arm B: Ironotecan + Cetuximab | Active comparator | Drug: Irinotecan, Biological: Cetuximab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Histological or cytological proof of colon or rectal adenocarcinoma
- Measurable site of disease according to RECIST that has not been previously irradiated
- Must have metastatic colorectal cancer which progressed after first line chemotherapy +/- bevacizumab
- Blood sample collected within 21 days prior to being registered for protocol therapy for UTG1A1 genotype analysis. (Patients with the UGT1A1 *28 7/7 genotype (homozygosity for the TA7 allele) will be excluded from the Phase I stage of the study. During the Phase II stage of the study, subjects will be allowed to participate but must begin treatment at dose level -1 of irinotecan.)
- A history of other malignancies (non-colorectal) is allowed, provided it has been curatively treated and demonstrates no evidence for recurrence of that cancer
Key exclusion criteria (17 listed)
- No more than one prior chemotherapy regimen for metastatic colorectal cancer, at least 28 days prior to being registered for protocol therapy
- No prior treatment with cetuximab
- No prior treatment with an mTOR inhibitor
- No known hypersensitivity to cetuximab, RAD001 (everolimus), other rapamycins (sirolimus, temsirolimus) or to its excipients
- No treatment with any investigational agent within 28 days prior to being registered for protocol 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 |
|---|---|---|
| IrinotecanIrinotecan 125 mg/m2 IV days 1 and 8 | Drug | Arm A: Irinotecan + Cetuximab +/- RAD001, Arm B: Ironotecan + Cetuximab |
| CetuximabCetuximab 250mg/m2 IV days 1, 8 and 15 | Biological | Arm A: Irinotecan + Cetuximab +/- RAD001, Arm B: Ironotecan + Cetuximab |
| RAD001Patients on Arm A will crossover and receive RAD001 at disease progression | Biological | Arm A: Irinotecan + Cetuximab +/- RAD001 |
Primary outcome
To determine the MTD of RAD001 in combination with irinotecan and cetuximab as second line therapy in patients with metastatic colorectal cancer
Time frame: Phase I
To evaluate the objective response (CR or PR) rates of patients treated with irinotecan and cetuximab with or without RAD001 in patients with metastatic colorectal cancer
Time frame: Phase II
2 secondary outcomes
To evaluate the pharmacokinetic (PK) profile for RAD001 after one cycle of therapy, on cycle 2 day 1
Time frame: Phase I
To evaluate the time to progression, duration of objective response (CR or PR) and overall survival of patients treated with irinotecan and cetuximab with or without RAD001
Time frame: Phase II
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 15 May 2015.
- Results publicationChiorean EG, Picus J, Breen T, Ansari RH, Harb WA, Burns M, Spittler AJ, Loehrer PJ. Phase I/II study of everolimus (E) with irinotecan (Iri) and cetuximab (C) in 2nd line metastatic colorectal cancer (mCRC): Hoosier Cancer Research Network GI05-102. J Clin Oncol 33:5s, 2015 (suppl; abstr 3618)
- Hoosier Cancer Research Network HomepageLink provided by the sponsor.
Related trials for Colorectal Cancer
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
RecruitingPhase 1
A Study of MGC030 in Participants With Advanced Solid Tumors
Urothelial Cancer, GastroEsophageal Cancer
Active, not recruitingObservational study
The IMPACT Study - Identification of Men With a Genetic Predisposition to ProstAte Cancer
Prostate Cancer, BRCA Mutation
RecruitingObservational study
ABCSG R07 Rectal Cancer Registry
Rectal Cancer, Adenocarcinoma of Rectum
Recruiting
Mainstreaming Genetics: Evaluation of a Digital Application to Scale and Spread Oncologist-initiated Genetic Testing
Cancer, Breast Cancer
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.
Gabriela Chiorean, M.D. study chair
Hoosier Oncology Group, Inc.
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Irinotecan, Cetuximab and RAD001 in people with Colorectal Cancer, run by Hoosier Cancer Research Network at 14 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 10 inclusion and 17 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 15 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 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 combined 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.
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?
To determine the MTD of RAD001 in combination with irinotecan and cetuximab as second line therapy in patients with metastatic colorectal cancer (time frame: Phase I). The study lists 2 primary outcomes in all. 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 NCT00522665, 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 15 May 2015.