Colorectal CancerPhase 2NCT00419159
Efficacy and Safety of Everolimus in Patients With Metastatic Colorectal Cancer Who Have Failed Prior Targeted Therapy and Chemotherapy
A Phase 2 study testing Everolimus (RAD001) in people with Colorectal Cancer, run by Novartis Pharmaceuticals at 1 site in United States.
Trial summary
To assess the safety and efficacy of weekly (70 mg per week) and daily (10 mg per day) everolimus in patients with metastatic colorectal cancer whose cancer has progressed despite prior treatment with targeted therapy and 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?
- Everolimus (RAD001)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 199 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2006to Mar 2009
- Phase
- Phase 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
- Age ≥ 18 years old.
- Patients with metastatic colorectal cancer (CRC).
- Patients must have sufficient and obtainable tumor tissue for biomarker analysis from original surgical resection.
- Patients with documented disease progression within 6 months of their most recent dose of chemotherapeutic regimens.
- Patients with at least one measurable lesion.
- Adequate bone marrow function.
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- Adequate liver function.
- Adequate renal function.
- Patients with a life expectancy of > 3 months.
- Patients with a World Health Organization (WHO) performance status of 0, 1, or 2.
- Women of childbearing potential must have had a negative serum pregnancy test 72 hours prior to the administration of the first study treatment.
- Patients who give a written informed consent obtained according to local guidelines.
Who cannot join
- Patients currently receiving anti-cancer agents or who have received these within 4 weeks prior to study entry.
- Patients who have previously received RAD001.
- Patients with a known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients.
- Chronic treatment with steroids or another immunosuppressive agent.
- Patients with untreated central nervous system (CNS) metastases or neurologically unstable CNS metastases.
- HIV seropositivity.
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- Patients with an active, bleeding diathesis. Patients may use enoxaparin.
- Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study.
- Patients who have a history of another primary malignancy < 3 years, with the exceptions of non-melanoma skin cancer, and carcinoma in situ of uterine cervix.
- Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods.
- Patients who are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to first study treatment.
- Patients unwilling to or unable to comply with the protocol.
- Other protocol defined inclusion/exclusion criteria may apply
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single Arm, Multicenter Phase II Study of Everolimus in Patients With Metastatic Colorectal Adenocarcinoma Whose Cancer Has Progressed Despite Prior Therapy With an Anti-EGFR Antibody (if Appropriate), Bevacizumab, Fluoropyrimidine, Oxaliplatin, and Irinotecan-based Regimens
To assess the safety and efficacy of weekly (70 mg per week) and daily (10 mg per day) everolimus in patients with metastatic colorectal cancer whose cancer has progressed despite prior treatment with targeted therapy and chemotherapy.
- Conditions
- Colorectal Cancer
- Being tested
- Everolimus (RAD001)
- Keywords
- Colorectal cancer, metastatic colorectal adenocarcinoma, anti-EGFR antibody
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Everolimus (RAD001)Drug
Also called Afinitor, Zortress, Certican
Everolimus was supplied in 5 mg tablets in blister packs.
| Study group | Role | What they receive |
|---|---|---|
| Everolimus (RAD001) 70 mg/week | Experimental | Not described Receives: Drug: Everolimus (RAD001) |
| Everolimus (RAD001) 10 mg/day | Experimental | Not described Receives: Drug: Everolimus (RAD001) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease Control Rate (DCR) and Objective Response Rate (ORR) According to the Response Evaluation Criteria in Solid Tumors (RECIST)
RECIST (Response Evaluation Criteria In Solid Tumors) is a set of published rules that define when cancer patients improve ("respond"), stay the same ("stable") or worsen ("progression") during treatments.
Disease Control Rate (DCR) defined as the percentage of participants with Disease Control best overall response (complete response, partial response or stable disease)and Objective Response Rate (ORR) defined as the percentage of participants with best overall Objective Response (complete response or partial response).
Measured: Imaging every 8 weeks
The Number of Participants With Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST)
RECIST (Response Evaluation Criteria In Solid Tumors) is a set of published rules that define when cancer patients improve ("respond"), stay the same ("stable") or worsen ("progression") during treatments.
Best Over Response (BOR): Complete Response (CR, No lesions), Partial Response (PR, 30% decrease in lesions), and Stable Disease (SD, none of the above)
Measured: Imaging every 8 weeks
Secondary outcomes (11)
Progression-free Survival (PFS)
Duration in months from the date of first study treatment to the date of the first documented disease progression or death due to any cause.
Measured: Imaging every 8 weeks
Overall Survival (OS)
Overall survival defined as the time from date of first study treatment to the date of death due to any cause.
Measured: Every 3 months
Number of Patients Who Died, Had an Serious Adverse Event (SAE), Had Grade 3 to 4 Adverse Event (AE), Discontinued Due to an AE, or Had a Clinical Notable AE by Treatment (tr).
Toxicity assessed using the NIH-NCI Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAEv3.0). On treatment death defined as deaths occurring no more than 28 days after the discontinuation of study treatment.
Measured: From the first day of treatment until 28 days after discontinuation of study treatment
Biomarker Predictive of Clinical Benefit (DCR by KRAS) on Everolimus (RAD001) 70 mg/Week
The efficacy variable compared in this biomarker analysis is disease control rate (DCR) within the 70mg/week arm in the analysis not adjusted for prognostic factors: from archival tumor tissue (and additionally from a biopsy at a metastatic site, if available), collected during screening: KRAS gene mutation. From blood plasma, collected at screening then on day 1 at cycles 2, 3 and 4, and at the end of treatment: blood lactate dehydrogenase (LDH) isoenzyme fractionation and serum levels of sVEGFR2, bFGF, PLGF and VEGF.
Measured: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
Biomarker Predictive of Clinical Benefit (DCR by KRAS) on Everolimus (RAD001) 10 mg/Day
The efficacy variable compared in this biomarker analysis is disease control rate (DCR) within the 10mg/day arm in the analysis not adjusted for prognostic factors: from archival tumor tissue (and additionally from a biopsy at a metastatic site, if available), collected during screening: KRAS gene mutation. From blood plasma, collected at screening then on day 1 at cycles 2, 3 and 4, and at the end of treatment: blood lactate dehydrogenase (LDH) isoenzyme fractionation and serum levels of sVEGFR2, bFGF, PLGF and VEGF.
Measured: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
Biomarkers Predictive of Clinical Benefit (Median PFS and OS by KRAS ) on Everolimus (RAD001) 70mg/Week
The efficacy variable that was compared in the biomarker analysis are Median progression free survival (PFS) and overall survival (OS) within the Everolimus (RAD001) 70mg/week arm in the analysis not adjusted for prognostic factors: from archival tumor tissue (and additionally from a biopsy at a metastatic site, if available), collected during screening: KRAS gene mutation. From blood plasma, collected at screening then on day 1 at cycles 2, 3 and 4, and at the end of treatment: blood lactate dehydrogenase (LDH) isoenzyme fractionation and serum levels of sVEGFR2, bFGF, PLGF and VEGF.
Measured: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
Biomarkers Predictive of Clinical Benefit (Median PFS and OS by KRAS) on Everolimus (RAD001) 10mg/Day
The efficacy variable that was compared in the biomarker analysis are Median progression free survival (PFS) and overall survival (OS) within the Everolimus (RAD001) 10mg/day arm in the analysis not adjusted for prognostic factors: from archival tumor tissue (and additionally from a biopsy at a metastatic site, if available), collected during screening: KRAS gene mutation. From blood plasma, collected at screening then on day 1 at cycles 2, 3 and 4, and at the end of treatment: blood lactate dehydrogenase (LDH) isoenzyme fractionation and serum levels of sVEGFR2, bFGF, PLGF and VEGF.
Measured: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
Biomarkers Predictive of Clinical Benefit (DCR by PTEN ) on Everolimus (RAD001) 70mg/Week
The efficacy variable that was compared in the biomarker analysis is DCR within the Everolimus (RAD001) 70mg/week arm in the analysis not adjusted for prognostic factors: from archival tumor tissue (and additionally from a biopsy at a metastatic site, if available), collected during screening: PTEN loss (imunohistochemistry, IHC), phosphoAKT (IHC), phosphoS6 (IHC), and p53 (IHC). From blood plasma, collected at screening then on day 1 at cycles 2, 3 and 4, and at the end of treatment: blood lactate dehydrogenase (LDH) isoenzyme fractionation and serum levels of sVEGFR2, bFGF, PLGF and VEGF.
Measured: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
Biomarkers Predictive of Clinical Benefit (DCR by PTEN ) on Everolimus (RAD001) 10mg/Day
The efficacy variable that was compared in the biomarker analysis is DCR within the Everolimus (RAD001) 10mg/day arm in the analysis not adjusted for prognostic factors: from archival tumor tissue (and additionally from a biopsy at a metastatic site, if available), collected during screening: PTEN loss (imunohistochemistry, IHC), phosphoAKT (IHC), phosphoS6 (IHC), and p53 (IHC). From blood plasma, collected at screening then on day 1 at cycles 2, 3 and 4, and at the end of treatment: blood lactate dehydrogenase (LDH) isoenzyme fractionation and serum levels of sVEGFR2, bFGF, PLGF and VEGF.
Measured: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
Biomarkers Predictive of Clinical Benefit (Median PFS and OS by PTEN ) on Everolimus (RAD001) 70mg/Week
The efficacy variable that was compared in the biomarker analysis are PFS \& OS within the Everolimus (RAD001) 70mg/Week arm in the analysis not adjusted for prognostic factors: from archival tumor tissue (and additionally from a biopsy at a metastatic site, if available), collected during screening: PTEN loss (imunohistochemistry, IHC), phosphoAKT (IHC), phosphoS6 (IHC), and p53 (IHC). From blood plasma, collected at screening then on day 1 at cycles 2, 3 and 4, and at the end of treatment: blood lactate dehydrogenase (LDH) isoenzyme fractionation and serum levels of sVEGFR2, bFGF, PLGF and VEGF.
Measured: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
Biomarkers Predictive of Clinical Benefit (Median PFS and OS by PTEN ) on Everolimus (RAD001) 10mg/Day
The efficacy variable that was compared in the biomarker analysis are PFS \& OS within the Everolimus (RAD001) 10mg/day arm in the analysis not adjusted for prognostic factors: from archival tumor tissue (and additionally from a biopsy at a metastatic site, if available), collected during screening: PTEN loss (imunohistochemistry, IHC), phosphoAKT (IHC), phosphoS6 (IHC), and p53 (IHC). From blood plasma, collected at screening then on day 1 at cycles 2, 3 and 4, and at the end of treatment: blood lactate dehydrogenase (LDH) isoenzyme fractionation and serum levels of sVEGFR2, bFGF, PLGF and VEGF.
Measured: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2007 (estimated)
- Study startDec 2006
- Primary completionMar 2009
- Study completionMar 2009
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.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 199 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00419159
- Sponsor's protocol ID
- CRAD001C2241
- Status last verified
- Apr 2019
- First submitted
- 4 Jan 2007
- Last updated
- 23 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm, Multicenter Phase II Study of Everolimus in Patients With Metastatic Colorectal Adenocarcinoma Whose Cancer Has Progressed Despite Prior Therapy With an Anti-EGFR Antibody (if Appropriate), Bevacizumab, Fluoropyrimidine, Oxaliplatin, and Irinotecan-based Regimens
- ClinicalTrials.gov ID
- NCT00419159
- Acronym / sponsor ID
- CRAD001C2241
- Conditions
- Colorectal Cancer
- Keywords
- Colorectal cancer, metastatic colorectal adenocarcinoma, anti-EGFR antibody
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 199 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Dec 2006
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 8 Jan 2007 (estimated)
- Results
- Posted 16 May 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To assess the safety and efficacy of weekly (70 mg per week) and daily (10 mg per day) everolimus in patients with metastatic colorectal cancer whose cancer has progressed despite prior treatment with targeted therapy and chemotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Everolimus (RAD001) 70 mg/week | Experimental | Drug: Everolimus (RAD001) |
| Everolimus (RAD001) 10 mg/day | Experimental | Drug: Everolimus (RAD001) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age ≥ 18 years old.
- Patients with metastatic colorectal cancer (CRC).
- Patients must have sufficient and obtainable tumor tissue for biomarker analysis from original surgical resection.
- Patients with documented disease progression within 6 months of their most recent dose of chemotherapeutic regimens.
- Patients with at least one measurable lesion.
Key exclusion criteria (13 listed)
- Patients currently receiving anti-cancer agents or who have received these within 4 weeks prior to study entry.
- Patients who have previously received RAD001.
- Patients with a known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients.
- Chronic treatment with steroids or another immunosuppressive agent.
- Patients with untreated central nervous system (CNS) metastases or neurologically unstable CNS metastases.
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 |
|---|---|---|
| Everolimus (RAD001)Also: Afinitor, Zortress, CerticanEverolimus was supplied in 5 mg tablets in blister packs. | Drug | Everolimus (RAD001) 10 mg/day, Everolimus (RAD001) 70 mg/week |
Primary outcome
Disease Control Rate (DCR) and Objective Response Rate (ORR) According to the Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: Imaging every 8 weeks
RECIST (Response Evaluation Criteria In Solid Tumors) is a set of published rules that define when cancer patients improve ("respond"), stay the same ("stable") or worsen ("progression") during treatments. Disease Control Rate (DCR) defined as the percentage of participants with Disease Control best overall response (complete response, partial response or stable disease)and Objective Response Rate (ORR) defined as the percentage of participants with best overall Objective Response (complete response or partial response).
The Number of Participants With Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: Imaging every 8 weeks
RECIST (Response Evaluation Criteria In Solid Tumors) is a set of published rules that define when cancer patients improve ("respond"), stay the same ("stable") or worsen ("progression") during treatments. Best Over Response (BOR): Complete Response (CR, No lesions), Partial Response (PR, 30% decrease in lesions), and Stable Disease (SD, none of the above)
11 secondary outcomes
Progression-free Survival (PFS)
Time frame: Imaging every 8 weeks
Overall Survival (OS)
Time frame: Every 3 months
Number of Patients Who Died, Had an Serious Adverse Event (SAE), Had Grade 3 to 4 Adverse Event (AE), Discontinued Due to an AE, or Had a Clinical Notable AE by Treatment (tr).
Time frame: From the first day of treatment until 28 days after discontinuation of study treatment
Biomarker Predictive of Clinical Benefit (DCR by KRAS) on Everolimus (RAD001) 70 mg/Week
Time frame: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
Biomarker Predictive of Clinical Benefit (DCR by KRAS) on Everolimus (RAD001) 10 mg/Day
Time frame: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
Biomarkers Predictive of Clinical Benefit (Median PFS and OS by KRAS ) on Everolimus (RAD001) 70mg/Week
Time frame: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
Biomarkers Predictive of Clinical Benefit (Median PFS and OS by KRAS) on Everolimus (RAD001) 10mg/Day
Time frame: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
Biomarkers Predictive of Clinical Benefit (DCR by PTEN ) on Everolimus (RAD001) 70mg/Week
Time frame: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
Biomarkers Predictive of Clinical Benefit (DCR by PTEN ) on Everolimus (RAD001) 10mg/Day
Time frame: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
Biomarkers Predictive of Clinical Benefit (Median PFS and OS by PTEN ) on Everolimus (RAD001) 70mg/Week
Time frame: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
Biomarkers Predictive of Clinical Benefit (Median PFS and OS by PTEN ) on Everolimus (RAD001) 10mg/Day
Time frame: Screening and Day 1 of cycles 2, 3, 4 and end of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.Link provided by the sponsor.
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Everolimus (RAD001) in people with Colorectal Cancer, run by Novartis Pharmaceuticals at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 13 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 23 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 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 16 May 2011). 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?
Disease Control Rate (DCR) and Objective Response Rate (ORR) According to the Response Evaluation Criteria in Solid Tumors (RECIST) (time frame: Imaging every 8 weeks). 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?
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 23 Apr 2019.