Colorectal CancerPhase 1/2NCT01047293
RAD001, FOLFOX and Bevacizumab in Treatment of Colorectal Carcinoma
A Phase 1/2 study testing RAD001, FOLFOX and Bevacizumab in people with Colorectal Cancer, run by University of Utah at 2 sites in United States.
Trial summary
RAD001 (everolimus) is a novel oral derivative of rapamycin. RAD001 has been in clinical development since 1996 as an immunosuppressant in solid organ transplantation and has obtained marketing authorization (Certican®) for prophylaxis of rejection in renal and cardiac transplantation in a number of countries… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- RAD001, FOLFOX and Bevacizumab
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2010to Aug 2015
- Phase
- Phase 1/2
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with advanced or metastatic colorectal cancers for whom chemotherapy is indicated
- Patients must not have had prior chemotherapy for advanced or metastatic disease. Patients could have received adjuvant chemotherapy or adjuvant chemo-radiotherapy
- Patients must have at least one measurable site of disease according to RECIST (version 1.1) criteria that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation
- Age ≥ 18 years
- Minimum of four weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy (adequately recovered from the acute toxicities of any prior therapy)
- ECOG performance status £ 2
Show all 12Show fewer
- Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hgb > 9 g/dL
- Adequate liver function as shown by: serum bilirubin ≤ 1.5 x upper limit of normal (ULN), and serum AST and ALT ≤ 2.5 x ULN. With the exception of serum AST and ALT (< 5 x ULN) if the patient has liver metastases
- Adequate renal function, serum creatinine < 2 x ULN or creatinine clearance > 50 cc/hr
- Fasting serum cholesterol ≤300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In cases where one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication
- Signed informed consent
- INR and PTT < 1.5 (Anticoagulation is allowed if target INR < 1.5 on a stable dose of warfarin or on a stable dose of LMW heparin for > 2 weeks at time of randomization)
Who cannot join
- History of severe and uncontrolled allergic reactions to bevacizumab
- Symptomatic congestive heart failure of New York heart association Class III or IV
- Patients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus)
- DVT and hypertension controlled < 6 months
- Prior treatment with any investigational drug within the preceding 4 weeks
- Chronic treatment with systemic steroids or another immunosuppressive agent; topical or inhaled corticosteroids are allowed
Show all 23Show fewer
- Patients should not receive immunization with attenuated live vaccines during study period or within 1 week of study entry
- Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
- Other malignancies that are active at the time of enrollment/ treatment on the protocol
- Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
- unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤ 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
- severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air
- uncontrolled diabetes as defined by fasting serum glucose >1.5x ULN
- any active (acute or chronic) or uncontrolled infection/ disorders
- nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy
- known liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
- A known history of HIV seropositivity
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 in the judgment of the investigator (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
- Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose Coumadin)
- Women who are pregnant or breast feeding, or women/men able to conceive and unwilling to practice an effective method of birth control. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of RAD001). Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study.
- Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients
- History of noncompliance to medical regimens
- Patients unwilling to or unable to comply with the protocol
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
Utah Cancer Specialists
Salt Lake City, Utah
About this study
Official title: A Phase I/II Study of RAD001, FOLFOX and Bevacizumab in Treatment of Colorectal Carcinoma
RAD001 (everolimus) is a novel oral derivative of rapamycin. RAD001 has been in clinical development since 1996 as an immunosuppressant in solid organ transplantation and has obtained marketing authorization (Certican®) for prophylaxis of rejection in renal and cardiac transplantation in a number of countries, including the majority of the European Union. RAD001 has been in development for patients with various malignancies since 2002.
RAD001 is being investigated as an anticancer agent based on its potential to act:
Read more
- Directly on the tumor cells by inhibiting tumor cell growth and proliferation
- Indirectly by inhibiting angiogenesis leading to reduced tumor vascularity (via potent inhibition of tumor cell HIF-1 activity, VEGF production and VEGF-induced proliferation of endothelial cells). The role of angiogenesis in the maintenance of solid tumor growth is well established, and the mTOR pathway has been implicated in the regulation of tumor production of proangiogenic factors as well as modulation of VEGFR signaling in endothelial cells.
At weekly and daily schedules and at various doses explored, RAD001 is generally well tolerated. The most frequent adverse events (rash, mucositis, fatigue and headache) associated with RAD001 therapy are manageable. Non-infectious pneumonitis has been reported with mTOR inhibitors but is commonly low-grade and reversible.
Both FOLFOX and bevacizumab are well established for treatment of metastatic colorectal carcinomas. FOLFOX-6 can be combined safely with Bevacizumab and is currently in phase 3 testing for adjuvant therapy and is commonly used as a first line treatment regimen for metastatic colorectal cancers 25. There is an enhanced interest in development of more effective regimens for colorectal cancers. RAD001 is a mTOR inhibitor that has preclinical and clinical activity in colorectal cancers. RAD001 downregulates the mTOR pathway which can lead to direct antiproliferative effects as well as decreased production of Vascular Endothelial Growth Factor. A combination of RAD001 at 10 mg per day in combination with Bevacizumab 10 mg/kg every 2 weeks has been shown to be efficacious and safe. In another trial, RAD001 was shown to have many patients with stable disease and clearly needs to be given in combination therapy.
Read the detailed description
Patient population Phase I portion: Metastatic colorectal cancer. A total of 3 patients on each cohort. Additional 3 patients on the tolerable cohort. Total patient number: Minimum 6, Maximum: 12 Phase II portion: Metastatic colorectal cancer: A total of 33 patients will be treated in this portion. This will include the patients treated on the tolerable dose level from the phase I trial. The statistical justification is indicated in the Statistics section 7.
Overall study design Phase I Study: A three cohort dose escalation will be used. Cycle length will be 28 days.
Bevacizumab FOLFOX-6 RAD001 Cohort 1: 5 mg/ kg Q 2weeks Standard Dose FOLFOX-6 2.5 mg PO qd Cohort 2: 5 mg/ kg Q 2weeks Standard Dose FOLFOX-6 5 mg PO qd Cohort 3: 5mg/kg Q 2 weeks Standard Dose FOLFOX-6 10 mg PO qd
Phase II Study:
For the Phase II portion the primary endpoint is Progression Free Survival at 6 months.
Study Objectives Primary
- To evaluate the progression free survival (PFS) for a combination of FOLFOX+ Bevacizumab + RAD001 in previously untreated metastatic or advanced colorectal cancers
- To evaluate the safety of the combination at a daily dosing of 2.5mg RAD001, 5 mg RAD001 or 10 mg RAD001 (Phase 1 part) Secondary
- To study the toxicity profile of the combination 2. To study the Response Rate (RR) of the combination 3. To determine the serum proteomic profiles of patients treated with combination therapy (Both phase I and II portions)
Dose selection for RAD001 In phase 1 clinical studies of RAD001 as a monotherapy agent in oncology patients, the side-effect profile is essentially mild to moderate adverse events with a low frequency of DLT at the daily dose of 10 mg/d. Based on the PK/PD model, a daily dose of 10mg RAD001 is assumed to provide a persistently high degree of target inhibition in the tumor [Investigators' Brochure-Section 4.1.1.3]. In addition, preliminary data from phase 1 studies, in which changes in molecular characteristics of tumor induced by treatment with RAD001 at the doses of 5 and 10 mg/d were investigated, confirm the pharmacodynamic activity predicted previously by PK/PD modeling [Investigators' Brochure-Section 4.1.1.3]. Therefore, a dose of 10 mg/d should ensure adequate drug target inhibition for most patients, taking into consideration the known inter-patient variability in drug levels (CV of approx 50%). In this study, we will begin with a RAD001 dose of 2.5 mg which is the lowest dose that can be administered on a daily basis. If the dose is tolerable (<1/6 DLTs), we will escalate to the dose of RAD001 (5 mg) and a third cohort of 10 mg. If cohort 1 is intolerable, study will be closed without any further expansion. On any dose level, 3 patients would be enrolled. If there are 0/3 DLTs, we would be able to escalate the dose level. If 1/3 DLTs are observed, 3 additional patients will be enrolled on the same dose level. The intent is to escalate dose levels only if < 1/6 DLTs are observed. In case 2 or more DLTs are observed on a particular dose level, no further dose escalation is possible. This dose level would be deemed intolerable and the lower dose level would be expanded. The definition of the Maximum Tolerated Dose (MTD) is the highest dose level at which RAD001 can be combined with FOLFOX/ Bevacizumab with < 1/6 DLTs.
FOLFOX/ Bevacizumab: FOLFOX6 and Bevacizumab will be given as previously described 28. mFOLFOX6 (oxaliplatin 85 mg/m2 IV with LV 350 mg IV over 2 hours plus FU 400 mg/m2 IV bolus and 2,400 mg/m2continuous infusion over 46 hours every 2 weeks) will be combined with Bevacizumab given at 5 mg/kg every 2 weeks. Dose modifications will be carried out for chemotherapy as per the label for oxaliplatin, fluorouracil and bevacizumab.
- Conditions
- Colorectal Cancer
- Being tested
- RAD001, FOLFOX, Bevacizumab
- Keywords
- 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.
RAD001Drug
Also called everlomius
RAD001 (everolimus) is a novel oral derivative of rapamycin.
RAD001 is being investigated as an anticancer agent based on its potential to act:
- Directly on the tumor cells by inhibiting tumor cell growth and proliferation
- Indirectly by inhibiting angiogenesis leading to reduced tumor vascularity (via potent inhibition of tumor cell HIF-1 activity, VEGF production and VEGF-induced proliferation of endothelial cells). The role of angiogenesis in the maintenance of solid tumor growth is well established, and the mTOR pathway has been implicated in the regulation of tumor production of proangiogenic factors as well as modulation of VEGFR signaling in endothelial cells.
FOLFOXDrug
Also called oxaliplatin + 5 FU + leucovorin
FOLFOX regimens combine oxaliplatin and leucovorin with bolus and infusional 5-fluorouracil (5-FU). 1 Oxaliplatin is a DNA cross-linking agent consisting of a platinum ion chelated with1, 2-diaminocyclohexane (DACH) and an oxalate ligand. It undergoes spontaneous activation in aqueous solutions via displacement of the labile oxalate ligand by water. The activated compounds bind with DNA, resulting in inter- and intra-strand platinum-DNA crosslinks. 5-FU is an anti-metabolite that blocks the methylation reaction of deoxyuridylic acid to thymidylic acid, causing thymidine-less cell death in rapidly growing cells. Leucovorin is reduced folic acid that modulates the activity of 5-FU by stabilizing the ternary 5-FdUMP/ thymidylate synthetase complex. Side effects associated with FOLFOX include neuropathy including pharyngo-laryngodysesthesia, diarrhea, nausea, vomiting, and mild myelosuppression.
BevacizumabDrug
Also called Avastin
Bevacizumab, a monoclonal antibody directed against VEGF (vascular endothelial growth factor) has been studied in a multitude of Phase I, II, and III clinical trials in more than 5000 patients in multiple tumor types. Phase III data in metastatic cancers
| Study group | Role | What they receive |
|---|---|---|
| All patients | Experimental | All participants enrolled. Receives: Drug: RAD001; Drug: FOLFOX; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival at Six Months
Measured: 6 months
Evaluate Safety of the Combination at a Daily Dosing of 2.5mg RAD001, 5 mg RAD001 or 10 mg RAD001 (Phase 1 Part)
Number of patients who experienced a Dose Limiting Toxicity (DLT). DLT will be assessed in the first 28 days of dosing. Patients need to get dosed with 2 rounds/sessions of all chemotherapy agents in the first 28 days in order to be evaluable for DLT assessment. The primary endpoint is safety as summarized by dose limiting toxicity (DLT).
Measured: December 2011
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2010 (estimated)
- Study startMay 2010
- Primary completionAug 2015
- Study completionAug 2015
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 Colorectal CancerStudies of the same condition, open and under way.
- More trials run by University of UtahThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Sunil Sharma, MD, Principal investigator, Huntsman Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01047293
- Sponsor's protocol ID
- HCI38815
- Status last verified
- Mar 2017
- First submitted
- 8 Jan 2010
- Last updated
- 4 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Weldon Gilcrease G, Stenehjem DD, Wade ML, Weis J, McGregor K, Whisenant J, Boucher KM, Thorne K, Orgain N, Garrido-Laguna I, Sharma S. Phase I/II study of everolimus combined with mFOLFOX-6 and bevacizumab for first-line treatment of metastatic colorectal cancer. Invest New Drugs. 2019 Jun;37(3):482-489. doi: 10.1007/s10637-018-0645-2. Epub 2018 Oct 10.
PubMed 30302599
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of RAD001, FOLFOX and Bevacizumab in Treatment of Colorectal Carcinoma
- ClinicalTrials.gov ID
- NCT01047293
- Acronym / sponsor ID
- HCI38815
- Conditions
- Colorectal Cancer
- Keywords
- colorectal cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- May 2010
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 12 Jan 2010 (estimated)
- Results
- Posted 6 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RAD001 (everolimus) is a novel oral derivative of rapamycin. RAD001 has been in clinical development since 1996 as an immunosuppressant in solid organ transplantation and has obtained marketing authorization (Certican®) for prophylaxis of rejection in renal and cardiac transplantation in a number of countries, including the majority of the European Union. RAD001 has been in development for patients with various malignancies since 2002.
RAD001 is being investigated as an anticancer agent based on its potential to act:
- Directly on the tumor cells by inhibiting tumor cell growth and proliferation
- Indirectly by inhibiting angiogenesis leading to reduced tumor vascularity (via potent inhibition of tumor cell HIF-1 activity, VEGF production and VEGF-induced proliferation of endothelial cells). The role of angiogenesis in the maintenance of solid tumor growth is well established, and the mTOR pathway has been implicated in the regulation of tumor production of proangiogenic factors as well as modulation of VEGFR signaling in endothelial cells.
At weekly and daily schedules and at various doses explored, RAD001 is generally well tolerated. The most frequent adverse events (rash, mucositis, fatigue and headache) associated with RAD001 therapy are manageable. Non-infectious pneumonitis has been reported with mTOR inhibitors but is commonly low-grade and reversible.
Both FOLFOX and bevacizumab are well established for treatment of metastatic colorectal carcinomas. FOLFOX-6 can be combined safely with Bevacizumab and is currently in phase 3 testing for adjuvant therapy and is commonly used as a first line treatment regimen for metastatic colorectal cancers 25. There is an enhanced interest in development of more effective regimens for colorectal cancers. RAD001 is a mTOR inhibitor that has preclinical and clinical activity in colorectal cancers. RAD001 downregulates the mTOR pathway which can lead to direct antiproliferative effects as well as decreased production of Vascular Endothelial Growth Factor. A combination of RAD001 at 10 mg per day in combination with Bevacizumab 10 mg/kg every 2 weeks has been shown to be efficacious and safe. In another trial, RAD001 was shown to have many patients with stable disease and clearly needs to be given in combination therapy.
Detailed description
Patient population Phase I portion: Metastatic colorectal cancer. A total of 3 patients on each cohort. Additional 3 patients on the tolerable cohort. Total patient number: Minimum 6, Maximum: 12 Phase II portion: Metastatic colorectal cancer: A total of 33 patients will be treated in this portion. This will include the patients treated on the tolerable dose level from the phase I trial. The statistical justification is indicated in the Statistics section 7.
Overall study design Phase I Study: A three cohort dose escalation will be used. Cycle length will be 28 days.
Bevacizumab FOLFOX-6 RAD001 Cohort 1: 5 mg/ kg Q 2weeks Standard Dose FOLFOX-6 2.5 mg PO qd Cohort 2: 5 mg/ kg Q 2weeks Standard Dose FOLFOX-6 5 mg PO qd Cohort 3: 5mg/kg Q 2 weeks Standard Dose FOLFOX-6 10 mg PO qd
Phase II Study:
For the Phase II portion the primary endpoint is Progression Free Survival at 6 months.
Study Objectives Primary
- To evaluate the progression free survival (PFS) for a combination of FOLFOX+ Bevacizumab + RAD001 in previously untreated metastatic or advanced colorectal cancers
- To evaluate the safety of the combination at a daily dosing of 2.5mg RAD001, 5 mg RAD001 or 10 mg RAD001 (Phase 1 part) Secondary
- To study the toxicity profile of the combination 2. To study the Response Rate (RR) of the combination 3. To determine the serum proteomic profiles of patients treated with combination therapy (Both phase I and II portions)
Dose selection for RAD001 In phase 1 clinical studies of RAD001 as a monotherapy agent in oncology patients, the side-effect profile is essentially mild to moderate adverse events with a low frequency of DLT at the daily dose of 10 mg/d. Based on the PK/PD model, a daily dose of 10mg RAD001 is assumed to provide a persistently high degree of target inhibition in the tumor [Investigators' Brochure-Section 4.1.1.3]. In addition, preliminary data from phase 1 studies, in which changes in molecular characteristics of tumor induced by treatment with RAD001 at the doses of 5 and 10 mg/d were investigated, confirm the pharmacodynamic activity predicted previously by PK/PD modeling [Investigators' Brochure-Section 4.1.1.3]. Therefore, a dose of 10 mg/d should ensure adequate drug target inhibition for most patients, taking into consideration the known inter-patient variability in drug levels (CV of approx 50%). In this study, we will begin with a RAD001 dose of 2.5 mg which is the lowest dose that can be administered on a daily basis. If the dose is tolerable (<1/6 DLTs), we will escalate to the dose of RAD001 (5 mg) and a third cohort of 10 mg. If cohort 1 is intolerable, study will be closed without any further expansion. On any dose level, 3 patients would be enrolled. If there are 0/3 DLTs, we would be able to escalate the dose level. If 1/3 DLTs are observed, 3 additional patients will be enrolled on the same dose level. The intent is to escalate dose levels only if < 1/6 DLTs are observed. In case 2 or more DLTs are observed on a particular dose level, no further dose escalation is possible. This dose level would be deemed intolerable and the lower dose level would be expanded. The definition of the Maximum Tolerated Dose (MTD) is the highest dose level at which RAD001 can be combined with FOLFOX/ Bevacizumab with < 1/6 DLTs.
FOLFOX/ Bevacizumab: FOLFOX6 and Bevacizumab will be given as previously described 28. mFOLFOX6 (oxaliplatin 85 mg/m2 IV with LV 350 mg IV over 2 hours plus FU 400 mg/m2 IV bolus and 2,400 mg/m2continuous infusion over 46 hours every 2 weeks) will be combined with Bevacizumab given at 5 mg/kg every 2 weeks. Dose modifications will be carried out for chemotherapy as per the label for oxaliplatin, fluorouracil and bevacizumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All patients | Experimental | Drug: RAD001, Drug: FOLFOX, Drug: BevacizumabAll participants enrolled. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- Patients with advanced or metastatic colorectal cancers for whom chemotherapy is indicated
- Patients must not have had prior chemotherapy for advanced or metastatic disease. Patients could have received adjuvant chemotherapy or adjuvant chemo-radiotherapy
- Patients must have at least one measurable site of disease according to RECIST (version 1.1) criteria that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation
- Age ≥ 18 years
- Minimum of four weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy (adequately recovered from the acute toxicities of any prior therapy)
Key exclusion criteria (23 listed)
- History of severe and uncontrolled allergic reactions to bevacizumab
- Symptomatic congestive heart failure of New York heart association Class III or IV
- Patients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus)
- DVT and hypertension controlled < 6 months
- Prior treatment with any investigational drug within the preceding 4 weeks
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 |
|---|---|---|
| RAD001Also: everlomiusRAD001 (everolimus) is a novel oral derivative of rapamycin. RAD001 is being investigated as an anticancer agent based on its potential to act: * Directly on the tumor cells by inhibiting tumor cell growth and proliferation * Indirectly by inhibiting angiogenesis leading to reduced tumor vascularity (via potent inhibition of tumor cell HIF-1 activity, VEGF production and VEGF-induced proliferation of endothelial cells). The role of angiogenesis in the maintenance of solid tumor growth is well established, and the mTOR pathway has been implicated in the regulation of tumor production of proangiogenic factors as well as modulation of VEGFR signaling in endothelial cells. | Drug | All patients |
| FOLFOXAlso: oxaliplatin + 5 FU + leucovorinFOLFOX regimens combine oxaliplatin and leucovorin with bolus and infusional 5-fluorouracil (5-FU). 1 Oxaliplatin is a DNA cross-linking agent consisting of a platinum ion chelated with1, 2-diaminocyclohexane (DACH) and an oxalate ligand. It undergoes spontaneous activation in aqueous solutions via displacement of the labile oxalate ligand by water. The activated compounds bind with DNA, resulting in inter- and intra-strand platinum-DNA crosslinks. 5-FU is an anti-metabolite that blocks the methylation reaction of deoxyuridylic acid to thymidylic acid, causing thymidine-less cell death in rapidly growing cells. Leucovorin is reduced folic acid that modulates the activity of 5-FU by stabilizing the ternary 5-FdUMP/ thymidylate synthetase complex. Side effects associated with FOLFOX include neuropathy including pharyngo-laryngodysesthesia, diarrhea, nausea, vomiting, and mild myelosuppression. | Drug | All patients |
| BevacizumabAlso: AvastinBevacizumab, a monoclonal antibody directed against VEGF (vascular endothelial growth factor) has been studied in a multitude of Phase I, II, and III clinical trials in more than 5000 patients in multiple tumor types. Phase III data in metastatic cancers | Drug | All patients |
Primary outcome
Progression Free Survival at Six Months
Time frame: 6 months
Evaluate Safety of the Combination at a Daily Dosing of 2.5mg RAD001, 5 mg RAD001 or 10 mg RAD001 (Phase 1 Part)
Time frame: December 2011
Number of patients who experienced a Dose Limiting Toxicity (DLT). DLT will be assessed in the first 28 days of dosing. Patients need to get dosed with 2 rounds/sessions of all chemotherapy agents in the first 28 days in order to be evaluable for DLT assessment. The primary endpoint is safety as summarized by dose limiting toxicity (DLT).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30302599Weldon Gilcrease G, Stenehjem DD, Wade ML, Weis J, McGregor K, Whisenant J, Boucher KM, Thorne K, Orgain N, Garrido-Laguna I, Sharma S. Phase I/II study of everolimus combined with mFOLFOX-6 and bevacizumab for first-line treatment of metastatic colorectal cancer. Invest New Drugs. 2019 Jun;37(3):482-489. doi: 10.1007/s10637-018-0645-2. Epub 2018 Oct 10.
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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.
Sunil Sharma, MD principal investigator
Huntsman Cancer Institute
2 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 RAD001, FOLFOX and Bevacizumab in people with Colorectal Cancer, run by University of Utah 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 23 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 4 Apr 2017. 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 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?
Yes. Results are posted in the registry (first posted 6 Mar 2017). 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?
Progression Free Survival at Six Months (time frame: 6 months). 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 NCT01047293, 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 4 Apr 2017.