Colorectal CancerPhase 2NCT01110785
Simvastatin and Panitumumab in Treating Patients With Advanced or Metastatic Colorectal Cancer
A Phase 2 study testing panitumumab, simvastatin and laboratory biomarker analysis in people with Colorectal Cancer, run by Leiden University Medical Center at 4 sites in Netherlands.
Trial summary
RATIONALE: Simvastatin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. 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?
- panitumumab, simvastatin and laboratory biomarker analysis
- How many people
- 46 participants
- Where
- 4 sitesNetherlands
- Study dates
- Apr 2010to Apr 2012
- Phase
- Phase 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
DISEASE CHARACTERISTICS:
- Diagnosis of colorectal cancer
- Advanced or metastatic disease
- Failed prior fluorouracil-, oxaliplatin- and irinotecan-containing regimens
- In case of progressive disease within 6 months after start of adjuvant fluorouracil-, oxaliplatin-, and irinotecan-containing regimens, the adjuvant therapy is considered to be treatment for metastatic disease
- Mutant-type k-ras status (mutation in codon 12, 13, or 61) on tumor material
- Measurable disease according to RECIST criteria version 1.1
- Progressive disease in the past 3 months according to RECIST criteria version 1.1
- No symptomatic brain metastases, defined as any symptoms during the past 6 months
PATIENT CHARACTERISTICS:
- WHO performance status 0-2
- WBC ≥ 2.0 x 10^9/L
- ANC ≥ 1.5 x 10^9/L
- Platelet count ≥ 100 x 10^9/L
- Hemoglobin ≥ 9 g/dL
- Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST/ALT ≤ 3 times ULN (≤ 5 times ULN in case of liver metastases)
- Creatinine clearance ≥ 60 mL/min
- Magnesium normal
- Calcium normal
- Creatine phosphokinase ≤ 2.5 times ULN
- Not pregnant or nursing
- Not planning to become pregnant within 6 months after the end of study treatment
- Fertile patients must use highly effective contraception during and for 6 months after completion of study therapy
- No noncompliance in previous studies
- No alcohol use > 4 units/day or unwilling to abstain from use
- No history of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or signs of interstitial lung disease on baseline CT scan
- No clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, or serious uncontrolled cardiac arrhythmia) < 1 year prior to study
- No symptomatic hypothyroidism
- No history of toxicity during statin use
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior EGFr-therapy, including monoclonal antibodies (e.g., panitumumab or cetuximab)
- No concurrent verapamil, amiodarone, or dronedarone or unwilling to abstain from use
Trial locations and contacts
4 sites in 1 country.
Netherlands4 sites, 4 recruiting
- Recruiting
Reinier de Graaf Group - Delft
Delft, 2625 AD
Contact Person, 31-15-260-3060
- Recruiting
Leiden University Medical Center
Leiden, 2333 ZA
Contact Person, 31-71-526-3486
- Recruiting
Diaconessenhuis Leiden
Leiden, 2334 CK
Contact Person, 31-71-517-8178
- Recruiting
HagaZiekenhuis - Locatie Leyenburg
The Hague, 2545 CH
Contact Person, 31-70-210-0000
About this study
Official title: Safety and Efficacy of the Addition of Simvastatin to Panitumumab in K-ras Mutant Advanced or Metastatic Colorectal Cancer Patients. A Single-Arm, Multicenter, Phase II Study Using a Simon Two Stage Design.
RATIONALE: Simvastatin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving simvastatin together with panitumumab may kill more tumor cells.
PURPOSE: This phase II trial is studying how well simvastatin given together with panitumumab works in treating patients with advanced or metastatic colorectal cancer.
Read the detailed description
OBJECTIVES:
Primary
- To determine if the proportion (at least 40%) of patients with K-ras mutant-type advanced or metastatic colorectal cancer are free from progression and alive based on RECIST criteria version 1.1 at 11 weeks after the first administration of panitumumab (i.e., 12.5 weeks after the scan at baseline at start of simvastatin).
- To determine if these results are comparable with historical results of k-ras wild-type colorectal carcinoma patients treated with panitumumab.
- To evaluate clinical signs of progression (according to RECIST criteria) in patients treated with this regimen.
Secondary
- To evaluate the safety of this regimen in these patients who have failed prior treatment with fluorouracil-, oxaliplatin-, and irinotecan-containing regimens.
- To evaluate the overall survival of patients who are treated with this regimen and have failed prior fluorouracil-, oxaliplatin-, and irinotecan-containing regimens.
- To evaluate the progression-free survival (based on RECIST criteria version 1.1) of these patients.
- To evaluate the objective response rate (based on RECIST criteria version 1.1) in these patients.
- To evaluate the correlation between skin toxicity and anti-tumor response in these patients.
Tertiary (exploratory)
- To evaluate the role of serum cholesterol as a biomarker during treatment with panitumumab and simvastatin.
- To correlate levels of serum cholesterol with treatment response and other factors, until progression of disease occurs.
- To investigate whether PTEN, PIK3CA, b-raf, ERK, and MEK status correlate with response to panitumumab in these patients.
- To investigate the role of single nucleotide polymorphisms related to the efficacy and metabolism of panitumumab as a predictor for response to panitumumab.
- To investigate the role of proteomics (e.g., EGF) as potential predictive markers for response to panitumumab and as potential biomarkers during treatment with panitumumab.
OUTLINE: This is a multicenter study.
Patients receive oral simvastatin once daily on days 1-14 and panitumumab IV over 30-90 minutes on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically for biomarker and other analyses.
After completion of study treatment, patients are followed for 30 days and then every 3 months thereafter.
- Conditions
- Colorectal Cancer
- Being tested
- panitumumab, simvastatin, laboratory biomarker analysis
- Keywords
- recurrent colon cancer, stage III colon cancer, stage IV colon cancer, recurrent rectal cancer, stage III rectal cancer, stage IV rectal cancer
- Medical subject headings
- Colorectal Neoplasms, Colonic Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
panitumumabBiological
simvastatinDrug
laboratory biomarker analysisOther
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients free from progression and alive at 11 weeks after the first dose of panitumumab measured by RECIST v 1.1
Secondary outcomes (9)
Toxicity measured by NCICTC v 3.0
Median and mean overall survival
Median and mean progression-free survival
Objective response rate
Correlation between skin toxicity and response to treatment
Serum cholesterol and subsequent treatment response
Correlation between PTEN, PIK3CA, b-raf, ERK, and MEK status and objective response rate
Correlation between single nucleotide polymorphisms and objective response rate
Correlation between proteomics and objective response rate
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2010 (estimated)
- Study startApr 2010
- Primary completionApr 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe 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
- Masking
- None (open label)
- Enrolment
- 46 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Investigators
- Hans Gelderblom, MD, PhD, Principal investigator, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01110785
- Sponsor's protocol ID
- CDR0000671002
- Other IDs
- DUT-LUMC-30012009, EUDRACT-2009-014452-30, EU-21033, DUT-LUMC-RASTAT-P, NL-29611-058-09
- Status last verified
- Apr 2011
- First submitted
- 23 Apr 2010
- Last updated
- 17 Sep 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of the Addition of Simvastatin to Panitumumab in K-ras Mutant Advanced or Metastatic Colorectal Cancer Patients. A Single-Arm, Multicenter, Phase II Study Using a Simon Two Stage Design.
- ClinicalTrials.gov ID
- NCT01110785
- Acronym / sponsor ID
- CDR0000671002
- Conditions
- Colorectal Cancer
- Keywords
- recurrent colon cancer, stage III colon cancer, stage IV colon cancer, recurrent rectal cancer, stage III rectal cancer, stage IV rectal cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 46 participants (estimated)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Study start
- Apr 2010
- Primary completion
- Apr 2012 (estimated)
- First posted
- 27 Apr 2010 (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.
RATIONALE: Simvastatin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving simvastatin together with panitumumab may kill more tumor cells.
PURPOSE: This phase II trial is studying how well simvastatin given together with panitumumab works in treating patients with advanced or metastatic colorectal cancer.
Detailed description
OBJECTIVES:
Primary
- To determine if the proportion (at least 40%) of patients with K-ras mutant-type advanced or metastatic colorectal cancer are free from progression and alive based on RECIST criteria version 1.1 at 11 weeks after the first administration of panitumumab (i.e., 12.5 weeks after the scan at baseline at start of simvastatin).
- To determine if these results are comparable with historical results of k-ras wild-type colorectal carcinoma patients treated with panitumumab.
- To evaluate clinical signs of progression (according to RECIST criteria) in patients treated with this regimen.
Secondary
- To evaluate the safety of this regimen in these patients who have failed prior treatment with fluorouracil-, oxaliplatin-, and irinotecan-containing regimens.
- To evaluate the overall survival of patients who are treated with this regimen and have failed prior fluorouracil-, oxaliplatin-, and irinotecan-containing regimens.
- To evaluate the progression-free survival (based on RECIST criteria version 1.1) of these patients.
- To evaluate the objective response rate (based on RECIST criteria version 1.1) in these patients.
- To evaluate the correlation between skin toxicity and anti-tumor response in these patients.
Tertiary (exploratory)
- To evaluate the role of serum cholesterol as a biomarker during treatment with panitumumab and simvastatin.
- To correlate levels of serum cholesterol with treatment response and other factors, until progression of disease occurs.
- To investigate whether PTEN, PIK3CA, b-raf, ERK, and MEK status correlate with response to panitumumab in these patients.
- To investigate the role of single nucleotide polymorphisms related to the efficacy and metabolism of panitumumab as a predictor for response to panitumumab.
- To investigate the role of proteomics (e.g., EGF) as potential predictive markers for response to panitumumab and as potential biomarkers during treatment with panitumumab.
OUTLINE: This is a multicenter study.
Patients receive oral simvastatin once daily on days 1-14 and panitumumab IV over 30-90 minutes on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically for biomarker and other analyses.
After completion of study treatment, patients are followed for 30 days and then every 3 months thereafter.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| panitumumab | Biological | – |
| simvastatin | Drug | – |
| laboratory biomarker analysis | Other | – |
Primary outcome
Percentage of patients free from progression and alive at 11 weeks after the first dose of panitumumab measured by RECIST v 1.1
9 secondary outcomes
Toxicity measured by NCICTC v 3.0
Median and mean overall survival
Median and mean progression-free survival
Objective response rate
Correlation between skin toxicity and response to treatment
Serum cholesterol and subsequent treatment response
Correlation between PTEN, PIK3CA, b-raf, ERK, and MEK status and objective response rate
Correlation between single nucleotide polymorphisms and objective response rate
Correlation between proteomics and objective response rate
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2013.
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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.
Hans Gelderblom, MD, PhD principal investigator
Leiden University Medical Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing panitumumab, simvastatin and laboratory biomarker analysis in people with Colorectal Cancer, run by Leiden University Medical Center at 4 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: status not confirmed, as of the sponsor's last update on 17 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Netherlands. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of patients free from progression and alive at 11 weeks after the first dose of panitumumab measured by RECIST v 1.1. 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 17 Sep 2013.