Gastrointestinal CancerPhase 1/2NCT01058655
RAD001 and AV-951 in Patients With Refractory, Metastatic Colorectal Cancer
A Phase 1/2 study testing Everolimus and Tivozanib in people with Gastrointestinal Cancer, run by Dana-Farber Cancer Institute at 3 sites in United States.
Trial summary
Research has shown that anti-angiogenic agents can be effective therapies to treat cancer. Anti-angiogenic agents target the blood vessels required for tumors to grow. Vascular endothelial growth factor (VEGF) is one of the cell pathways used for this blood vessel growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Cancer
- What is being tested?
- Everolimus and Tivozanib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 3 sitesUnited States
- Study dates
- Feb 2010to Apr 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years of age or older
- Histologic confirmation of a gastrointestinal malignancy, limited to cancer of the esophagus, stomach, small bowel, liver, biliary tract, gallbladder, pancreas, large bowel, appendix, rectum and anus.
- Locally advanced or metastatic disease
- Disease that: a) has recurred or progressed following standard therapy, b) for which no standard therapy currently exists, or c) for which the subject is not a candidate for or unwilling to undergo standard therapy. There is no limit to the number of prior regimens received by the patient.
- ECOG Performance Status of 0, 1 or 2
- Life expectancy of at least 12 weeks
Show all 23Show fewer
- Adequate organ function as outlined in the protocol
- At least 4 weeks is required from : a) previous regimen of chemotherapy, b) immunotherapy or biological therapy, c) other investigational agents, and d) radiotherapy.
- At least 4 weeks is required from treatment of bevacizumab
- At least 4 weeks is required from prior systemic hormonal therapy or treatment with strong CYP3A4 inducers or inhibitors
- If female and of child bearing potential, documentation of negative pregnancy test prior to enrollment.
- 18 years of age or older
- Histologic confirmation of colorectal cancer
- Stage IV disease
- At least one site of disease measurable by RECIST criteria
- Receipt of or intolerance to a fluoropyrimidine (fluorouracil or capecitabine), irinotecan, oxaliplatin, bevacizumab, and a monoclonal antibody to epidermal growth factor receptor (cetuximab or panitumumab). If a patient's tumor was K-RAS mutation positive, then previous treatment with cetuximab or panitumumab is not required.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- Life expectancy of at least 12 weeks
- Adequate organ function as outlined in the protocol
- At least 3 weeks is required from: (a) previous regimen of chemotherapy, (b)immunotherapy or biological therapy, (c) other investigational agents, and (d) radiotherapy. Of note, concomitant radiotherapy is NOT allowed, while a patient is on protocol.
- At least 3 weeks is required from prior treatment with bevacizumab
- At least 3 weeks is required since prior systemic hormonal therapy or treatment with strong CYP3A4 inducers or inhibitors.
- Negative pregnancy test for women of child bearing potential
Who cannot join
- Prior therapy with inhibitors of mTOR or VEGFR (prior treatment with bevacizumab is allowed).
- Clinically apparent CNS metastases or carcinomatous meningitis
- Clinically significant cardiovascular disease
- Major surgery within 4 weeks of the start of study treatment or patients who have not recovered from the side effects of any major surgery.
- Active bleeding diathesis or history of Grade 2 or greater clinically significant bleeding within 3 months of enrollment
- Active infection requiring antibiotics
Show all 38Show fewer
- Participants with a known positive history of chronic Hepatitis B viral infection or known positive HBV-DNA test are excluded.
- History of interstitial pneumonitis or severely impaired lung function defined as 88% or less O2 saturation at rest in room air
- Immunocompromise or chronic use of immunosuppressant medications
- Uncontrolled serious medical or psychiatric illness
- Subjects with non-healing wounds, active peptic ulcers, or unhealed bone fractures
- Significant proteinuria, defined as urine dipstick protein of 3+ or greater
- Concurrent malignancy (other than non-melanoma skin cancer) diagnosed within the past 3 years or any currently active malignancy
- Elevated fasting levels of the following: serum cholesterol, serum triglycerides, and serum glucose
- Patients who are pregnant or lactating
- Malabsorption, uncontrolled vomiting or diarrhea, or any disease significantly affecting gastrointestinal function that could interfere with absorption of study drugs
- Inability to swallow pills
- For the phase II component, only patients with metastatic colorectal cancer will be enrolled.
- For the Phase II component:
- Prior therapy with inhibitors of mTOR or VEGFR (prior treatment with bevacizumab is allowed)
- Clinically apparent CNS metastases or carcinomatous meningitis, as determined by physical examination and imaging studies
- Clinically significant cardiovascular disease, defined as follows:
- (A)Symptomatic congestive heart failure, (B)Symptomatic coronary artery disease or myocardial infarction within 3 months of enrollment, (C)Cardiac arrhythmias not controlled with medication, (D)Deep venous thrombosis or pulmonary embolus within the last 6 months, (E) Cerebrovascular accident within the last 12 months, (F)Poorly controlled hypertension, defined as systolic pressure > 150 mmHg or diastolic pressure > 100 mmHg documented on 2 consecutive measurements taken at least 24 hours apart, (G)Symptomatic peripheral vascular disease, defined as claudication on walking ≤
- 1 block
- Major surgery within 4 weeks of the start of study treatment or patients who have not recovered from the side effects of any major surgery. Major surgery defined as those surgeries that require general anesthesia
- Active bleeding diathesis or history of grade 2 or higher clinically significant bleeding (hemoptysis, hematemesis, hematochezia, or melena) within 3 months of enrollment
- Active infection requiring antibiotics
- Participants with a known positive history of chronic Hepatitis B viral infection or known positive HBV-DNA test are excluded.
- History of interstitial pneumonitis or severely impaired lung function defined as less than or equal to 88% O2 saturation at rest in room air.
- Immunocompromise or chronic use of immunosuppressant medications (prednisone ≤ 10 mg daily or the equivalent of a comparable steroid is allowed, if deemed necessary by a study investigator)
- Uncontrolled serious medical or psychiatric illness
- Subjects with non-healing wounds, active peptic ulcers, or unhealed bone fractures
- Significant proteinuria, defined as urine dipstick protein 3+ or greater
- Concurrent malignancy (other than non-melanoma skin cancer) diagnosed within the past 3 years or any currently active malignancy.
- Elevated fasting levels of the following: serum cholesterol, serum triglycerides, and serum glucose.
- Patients who are pregnant or lactating
- Malabsorption, uncontrolled vomiting or diarrhea, or any disease significantly affecting gastrointestinal function that could interfere with absorption of study drugs
- Inability to swallow pills
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: A Phase I/II Study of RAD001 and AV-951 in Patients With Refractory, Metastatic Colorectal Cancer
Research has shown that anti-angiogenic agents can be effective therapies to treat cancer. Anti-angiogenic agents target the blood vessels required for tumors to grow. Vascular endothelial growth factor (VEGF) is one of the cell pathways used for this blood vessel growth. When the investigators interfere with the VEGF pathway, the investigators inhibit this blood vessel growth which is required by tumors. One of the study drugs being used, tivozanib (AV-951), selectively interferes with the VEGF pathway. The second study drug being used, everolimus (RAD001) interferes with the mTOR pathway. The mTOR pathway is another pathway involved in blood vessel and tumor cell growth. By combining these two drugs the investigators hope to slow or reverse tumor cell growth in patients whose tumors have become resistant to other therapies for their disease.
Read the detailed description
Primary Objective
Phase I
- To determine the safety, tolerability, and maximally tolerated dose (MTD) of everolimus and tivozanib administered in combination to patients with advanced gastrointestinal tumors.
Phase II
- At the MTD, to assess progression-free survival associated with everolimus and tivozanib in patients with refractory, metastatic colorectal cancer.
Secondary Objectives
Phase II
- To assess tumor response rate.
- To assess overall survival.
- Conditions
- Gastrointestinal Cancer
- Being tested
- Everolimus, Tivozanib
- Keywords
- Colorectal Cancer
- Medical subject headings
- Gastrointestinal Neoplasms, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called RAD001, Afinitor
TivozanibDrug
Also called AV-951
| Study group | Role | What they receive |
|---|---|---|
| Phase I Cohort 1: Everolimus 5 mg + Tivozanib 1 mg | Experimental | Patients received oral everolimus daily continuously and oral tivozanib daily for 3 of a 4 weeks cycle. Patients are treated until disease progression, unacceptable toxicity or withdrawal of consent. Receives: Drug: Everolimus; Drug: Tivozanib |
| Phase I Cohort 2: Everolimus 10 mg + Tivozanib 1 mg | Experimental | Patients received oral everolimus daily continuously and oral tivozanib daily for 3 of a 4 weeks cycle. Patients are treated until disease progression, unacceptable toxicity or withdrawal of consent. Receives: Drug: Everolimus; Drug: Tivozanib |
| Phase I Cohort 3: Everolimus 10 mg + Tivozanib 1.5 mg | Experimental | Patients received oral everolimus daily continuously and oral tivozanib daily for 3 of a 4 weeks cycle. Patients are treated until disease progression, unacceptable toxicity or withdrawal of consent. Receives: Drug: Everolimus; Drug: Tivozanib |
| Phase II: Everolimus 10 mg + Tivozanib 1 mg | Experimental | Patients received oral everolimus daily continuously and oral tivozanib daily for 3 of a 4 weeks cycle. Patients are treated until disease progression, unacceptable toxicity or withdrawal of consent. Receives: Drug: Everolimus; Drug: Tivozanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Everolimus Maximum Tolerated Dose (MTD) [Phase I]
The everolimus MTD in combination with tivozanib is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If no DLTs are observed, the MTD is not reached.
Measured: Patients were assessed continuously for toxicity while on study. The observation period for MTD evaluation was the first 28 days (cycle 1) of treatment.
Tivozanib Maximum Tolerated Dose (MTD) [Phase I]
The tivozanib MTD in combination with everolimus is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If no DLTs are observed, the MTD is not reached.
Measured: Patients were assessed continuously for toxicity while on study. The observation period for MTD evaluation was the first 28 days (cycle 1) of treatment.
Dose Limiting Toxicity (DLT) [Phase I]
A DLT was defined as a treatment-related (attribution possible, probable, definite) adverse event that meets any of the following criteria: Grade 3 (G3) or higher non-hematologic toxicity (excluding, nausea, vomiting, diarrhea, alopecia, hypertension, hypercholesterolemia, or hypertriglyceridemia); G3 diarrhea, nausea or vomiting lasting > 48 hours or leading to hospitalization, despite aggressive anti-diarrheal or anti-emetic medications; G4 diarrhea, despite aggressive anti-diarrheal medications; G4 vomiting, despite aggressive anti-emetic medications; G3 hypertension, for which blood pressure cannot be reduced to <150/100 with anti-hypertensive therapies; G4 hypertension or severe hypertension, as defined by systolic blood pressure >180 mmHg or diastolic blood pressure > 110 mmHg; G4 hypercholesterolemia or hypertriglyceridemia lasting > 7 days, despite appropriate use of anti-hyperlipidemic medications; G4 hematologic toxicity lasting for >5 days, including leukopenia, neutropen
Measured: Patients were assessed continuously for toxicity while on study. The observation period for DLT evaluation was the first 28 days (cycle 1) of treatment.
Progression-Free Survival (PFS) [Phase II]
PFS based on the Kaplan-Meier method is defined as the time from study entry to the earliest documentation of disease progression (PD) or death. Participants alive without evidence of PD were censored at the earliest date of last disease assessment. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
Measured: Disease was assessed radiographically to document clinical progression every 2 cycles on treatment. Participants were followed for up to 16 months since study entry.
Secondary outcomes (2)
Disease Control Rate (DCR) [Phase II]
Disease Control Rate is defined as the percentage of patients who achieve confirmed stable disease (SD) or better on treatment based on RECIST 1.0 criteria. Per RECIST 1.0 for target lesions, complete response (CR) is disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. Progressive disease (PD) is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started. SD is neither PR nor PD. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Measured: Disease was assessed every 2 cycles on treatment. Median treatment duration on this study cohort was 2 months (range 1-16).
Overall Survival (OS) [Phase II]
OS based on the Kaplan-Meier method is defined as the time from study entry to death or date last known alive.
Measured: Long-term follow-up for survival was not specified per protocol. Participants were followed for up to 20 months on this study.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2010 (estimated)
- Study startFeb 2010
- Primary completionSep 2013
- Study completionApr 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 Gastrointestinal CancerStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Brigham and Women's Hospital, Massachusetts General Hospital, Beth Israel Deaconess Medical Center, Novartis, AVEO Pharmaceuticals, Inc.
- Responsible party
- Principal investigator, Brian Wolpin, MD, MPH, Dana-Farber Cancer Institute
- Investigators
- Brian Wolpin, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01058655
- Sponsor's protocol ID
- 09-276
- Status last verified
- Feb 2017
- First submitted
- 29 Oct 2009
- Last updated
- 13 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Wolpin BM, Ng K, Zhu AX, Abrams T, Enzinger PC, McCleary NJ, Schrag D, Kwak EL, Allen JN, Bhargava P, Chan JA, Goessling W, Blaszkowsky LS, Supko JG, Elliot M, Sato K, Regan E, Meyerhardt JA, Fuchs CS. Multicenter phase II study of tivozanib (AV-951) and everolimus (RAD001) for patients with refractory, metastatic colorectal cancer. Oncologist. 2013;18(4):377-8. doi: 10.1634/theoncologist.2012-0378. Epub 2013 Apr 11.
PubMed 23580238
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of RAD001 and AV-951 in Patients With Refractory, Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT01058655
- Acronym / sponsor ID
- 09-276
- Conditions
- Gastrointestinal Cancer
- Keywords
- Colorectal Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Brigham and Women's Hospital, Massachusetts General Hospital, Beth Israel Deaconess Medical Center, Novartis, AVEO Pharmaceuticals, Inc.
- Study start
- Feb 2010
- Primary completion
- Sep 2013 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 29 Jan 2010 (estimated)
- Results
- Posted 7 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Research has shown that anti-angiogenic agents can be effective therapies to treat cancer. Anti-angiogenic agents target the blood vessels required for tumors to grow. Vascular endothelial growth factor (VEGF) is one of the cell pathways used for this blood vessel growth. When the investigators interfere with the VEGF pathway, the investigators inhibit this blood vessel growth which is required by tumors. One of the study drugs being used, tivozanib (AV-951), selectively interferes with the VEGF pathway. The second study drug being used, everolimus (RAD001) interferes with the mTOR pathway. The mTOR pathway is another pathway involved in blood vessel and tumor cell growth. By combining these two drugs the investigators hope to slow or reverse tumor cell growth in patients whose tumors have become resistant to other therapies for their disease.
Detailed description
Primary Objective
Phase I
- To determine the safety, tolerability, and maximally tolerated dose (MTD) of everolimus and tivozanib administered in combination to patients with advanced gastrointestinal tumors.
Phase II
- At the MTD, to assess progression-free survival associated with everolimus and tivozanib in patients with refractory, metastatic colorectal cancer.
Secondary Objectives
Phase II
- To assess tumor response rate.
- To assess overall survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Phase I Cohort 1: Everolimus 5 mg + Tivozanib 1 mg | Experimental | Drug: Everolimus, Drug: TivozanibPatients received oral everolimus daily continuously and oral tivozanib daily for 3 of a 4 weeks cycle. Patients are treated until disease progression, unacceptable toxicity or withdrawal of consent. |
| Phase I Cohort 2: Everolimus 10 mg + Tivozanib 1 mg | Experimental | Drug: Everolimus, Drug: TivozanibPatients received oral everolimus daily continuously and oral tivozanib daily for 3 of a 4 weeks cycle. Patients are treated until disease progression, unacceptable toxicity or withdrawal of consent. |
| Phase I Cohort 3: Everolimus 10 mg + Tivozanib 1.5 mg | Experimental | Drug: Everolimus, Drug: TivozanibPatients received oral everolimus daily continuously and oral tivozanib daily for 3 of a 4 weeks cycle. Patients are treated until disease progression, unacceptable toxicity or withdrawal of consent. |
| Phase II: Everolimus 10 mg + Tivozanib 1 mg | Experimental | Drug: Everolimus, Drug: TivozanibPatients received oral everolimus daily continuously and oral tivozanib daily for 3 of a 4 weeks cycle. Patients are treated until disease progression, unacceptable toxicity or withdrawal of consent. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 18 years of age or older
- Histologic confirmation of a gastrointestinal malignancy, limited to cancer of the esophagus, stomach, small bowel, liver, biliary tract, gallbladder, pancreas, large bowel, appendix, rectum and anus.
- Locally advanced or metastatic disease
- Disease that: a) has recurred or progressed following standard therapy, b) for which no standard therapy currently exists, or c) for which the subject is not a candidate for or unwilling to undergo standard therapy. There is no limit to the number of prior regimens received by the patient.
- ECOG Performance Status of 0, 1 or 2
Key exclusion criteria (38 listed)
- Prior therapy with inhibitors of mTOR or VEGFR (prior treatment with bevacizumab is allowed).
- Clinically apparent CNS metastases or carcinomatous meningitis
- Clinically significant cardiovascular disease
- Major surgery within 4 weeks of the start of study treatment or patients who have not recovered from the side effects of any major surgery.
- Active bleeding diathesis or history of Grade 2 or greater clinically significant bleeding within 3 months of enrollment
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 |
|---|---|---|
| EverolimusAlso: RAD001, Afinitor | Drug | Phase I Cohort 1: Everolimus 5 mg + Tivozanib 1 mg, Phase I Cohort 2: Everolimus 10 mg + Tivozanib 1 mg, Phase I Cohort 3: Everolimus 10 mg + Tivozanib 1.5 mg, Phase II: Everolimus 10 mg + Tivozanib 1 mg |
| TivozanibAlso: AV-951 | Drug | Phase I Cohort 1: Everolimus 5 mg + Tivozanib 1 mg, Phase I Cohort 2: Everolimus 10 mg + Tivozanib 1 mg, Phase I Cohort 3: Everolimus 10 mg + Tivozanib 1.5 mg, Phase II: Everolimus 10 mg + Tivozanib 1 mg |
Primary outcome
Everolimus Maximum Tolerated Dose (MTD) [Phase I]
Time frame: Patients were assessed continuously for toxicity while on study. The observation period for MTD evaluation was the first 28 days (cycle 1) of treatment.
The everolimus MTD in combination with tivozanib is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If no DLTs are observed, the MTD is not reached.
Tivozanib Maximum Tolerated Dose (MTD) [Phase I]
Time frame: Patients were assessed continuously for toxicity while on study. The observation period for MTD evaluation was the first 28 days (cycle 1) of treatment.
The tivozanib MTD in combination with everolimus is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If no DLTs are observed, the MTD is not reached.
Dose Limiting Toxicity (DLT) [Phase I]
Time frame: Patients were assessed continuously for toxicity while on study. The observation period for DLT evaluation was the first 28 days (cycle 1) of treatment.
A DLT was defined as a treatment-related (attribution possible, probable, definite) adverse event that meets any of the following criteria: Grade 3 (G3) or higher non-hematologic toxicity (excluding, nausea, vomiting, diarrhea, alopecia, hypertension, hypercholesterolemia, or hypertriglyceridemia); G3 diarrhea, nausea or vomiting lasting > 48 hours or leading to hospitalization, despite aggressive anti-diarrheal or anti-emetic medications; G4 diarrhea, despite aggressive anti-diarrheal medications; G4 vomiting, despite aggressive anti-emetic medications; G3 hypertension, for which blood pressure cannot be reduced to <150/100 with anti-hypertensive therapies; G4 hypertension or severe hypertension, as defined by systolic blood pressure >180 mmHg or diastolic blood pressure > 110 mmHg; G4 hypercholesterolemia or hypertriglyceridemia lasting > 7 days, despite appropriate use of anti-hyperlipidemic medications; G4 hematologic toxicity lasting for >5 days, including leukopenia, neutropen
Progression-Free Survival (PFS) [Phase II]
Time frame: Disease was assessed radiographically to document clinical progression every 2 cycles on treatment. Participants were followed for up to 16 months since study entry.
PFS based on the Kaplan-Meier method is defined as the time from study entry to the earliest documentation of disease progression (PD) or death. Participants alive without evidence of PD were censored at the earliest date of last disease assessment. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
2 secondary outcomes
Disease Control Rate (DCR) [Phase II]
Time frame: Disease was assessed every 2 cycles on treatment. Median treatment duration on this study cohort was 2 months (range 1-16).
Overall Survival (OS) [Phase II]
Time frame: Long-term follow-up for survival was not specified per protocol. Participants were followed for up to 20 months on this study.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23580238Wolpin BM, Ng K, Zhu AX, Abrams T, Enzinger PC, McCleary NJ, Schrag D, Kwak EL, Allen JN, Bhargava P, Chan JA, Goessling W, Blaszkowsky LS, Supko JG, Elliot M, Sato K, Regan E, Meyerhardt JA, Fuchs CS. Multicenter phase II study of tivozanib (AV-951) and everolimus (RAD001) for patients with refractory, metastatic colorectal cancer. Oncologist. 2013;18(4):377-8. doi: 10.1634/theoncologist.2012-0378. Epub 2013 Apr 11.
- Individual participant dataSharing planned: No
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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.
Brian Wolpin, MD principal investigator
Dana-Farber Cancer Institute
3 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 Everolimus and Tivozanib in people with Gastrointestinal Cancer, run by Dana-Farber Cancer Institute at 3 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 23 inclusion and 38 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 13 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 3 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 7 Apr 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?
Everolimus Maximum Tolerated Dose (MTD) [Phase I] (time frame: Patients were assessed continuously for toxicity while on study. The observation period for MTD evaluation was the first 28 days (cycle 1) of treatment.). The study lists 4 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 NCT01058655, 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 13 Apr 2017.