Colorectal CancerPhase 2NCT01260415
A Study of Perioperative Chemotherapy Plus Panitumumab in Patients With Colorectal Cancer Liver Metastases
A Phase 2 study testing Panitumumab, Oxaliplatin, 5-FU in people with Colorectal Cancer and Liver Metastases, run by University Health Network, Toronto at 4 sites in Canada.
Trial summary
This is a phase II study to assess whether treatment with chemotherapy drugs FOLFOX (5-Fluorouracil (5FU), Oxaliplatin (Eloxatin) and Leucovorin (Folinic Acid)) or FOLFIRI (5-Fluorouracil (5FU), Irinotecan (Camptosar) and Leucovorin (Folinic Acid))and panitumumab before and after surgery can improve outcome in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Liver Metastases
- What is being tested?
- Panitumumab, Oxaliplatin, 5-FU
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 4 sitesCanada
- Study dates
- Aug 2010to Jun 2013
- 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
Who may be able to join
- Patients must have histologically or cytologically confirmed colorectal cancer with available tissue to test for K-RAS mutation. Biopsy is required if no archived tissue is available. K-RAS mutation status must be confirmed prior to registration. Only patients with K-RAS wild-type cancers are eligible.
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan.
- Patients must have resectable hepatic colorectal metastases.
- Patients may have synchronous unresected primary disease upon registration. Primary must be resectable, either at same laparotomy or at separate laparotomy from liver resection.
- Age >18 years.
- Patients must have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
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- Patients must have normal organ and marrow function as defined below:
- leukocytes > 3,000/mcL absolute neutrophil count >1,500/mcL platelets >100,000/mcL hemoglobin > 90 g/L total bilirubin < 2 x upper limit of normal (< 1.5 x ULN for FOLFIRI), AST(SGOT) and ALT(SGPT)< 5 x upper limit of normal (< 3 x ULN for FOLFIRI);creatinine within normal institutional limits OR- creatinine clearance >50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
- Appropriate imaging investigations, including CT or MRI of chest/abdomen/pelvis. Other scans if clinically indicated may be performed. All imaging studies must be performed within 28 days of study entry.
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study and for a period of six months after cessation of study therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients must have had no previous systemic treatment in the adjuvant or metastatic setting within 6 months of registration.
- Patients may not have had prior treatment with an EGFR antagonist.
- Patients may not have a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid malignancies curatively treated with no evidence of disease for ≥ 5 years.
- Patients may not have extrahepatic metastatic disease. Patients who have had prior surgical resection for hepatic metastases or extrahepatic disease (eg. pulmonary metastases) are also excluded from this study.
- Patients may not have pre-existing chronic hepatic disease (eg. cirrhosis, chronic active hepatitis B or C)
- History of allergic reactions, or intolerance, attributed to compounds of similar chemical or biologic composition to 5-fluorouracil, oxaliplatin, or panitumumab.
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- Patients being considered for irinotecan must not have a history of Gilbert's syndrome.
- Patients may not have uncontrolled inter-current illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
- HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the agents used in this study. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
- Patients with active cardiovascular disease, i.e., unstable angina, New York Heart Association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medications, or grade II or greater peripheral vascular disease. In addition, patients with arterial or venous thrombosis, myocardial infarction, and cerebral vascular accidents (stroke / transient ischemic attach (TIA)) within 6 months prior to study entry will be excluded.
- Patients with a history of interstitial pneumonitis or pulmonary fibrosis will be excluded.
- Organ allografts requiring immunosuppressive therapy.
Trial locations and contacts
4 sites in 1 country.
Canada4 sites
London Regional Cancer Centre
London, Ontario
The Ottawa Hospital Cancer Center
Ottawa, Ontario
Mount Sinai Hospital
Toronto, Ontario
Princess Margaret Hospital
Toronto, Ontario
About this study
Official title: A Phase II Study of Perioperative Chemotherapy Plus Panitumumab in Patients With Colorectal Cancer Liver Metastases
This is a phase II study to assess whether treatment with chemotherapy drugs FOLFOX (5-Fluorouracil (5FU), Oxaliplatin (Eloxatin) and Leucovorin (Folinic Acid)) or FOLFIRI (5-Fluorouracil (5FU), Irinotecan (Camptosar) and Leucovorin (Folinic Acid))and panitumumab before and after surgery can improve outcome in patients with liver metastases (the cancer has spread to other parts of the body such as the liver) that are resectable (can be surgically removed), from colorectal cancer that have a non mutant (wild-type) K-ras gene.
FOLFOX/FOLFIRI is an intravenous (given by vein) chemotherapy combination that is approved for colorectal cancer while panitumumab is also an intravenous drug and have been approved for treatment of refractory (not responding treatment) metastatic colorectal cancer whose cancers have the K-ras gene. These drugs are not approved for the treatment of colorectal cancer liver metastases (CRCLM) who can have surgery.
Read more
Patients will receive FOLFOX/FOLFIRI and panitumumab for four 2-week cycles before surgery. Surgery will be done no sooner than 4 weeks and no later than 8 weeks, after completion of the fourth cycle of chemotherapy.
If the liver metastases after the chemotherapy and surgery decreases or stops growing, then chemotherapy will be given after surgery. Treatments will start no sooner than 4 weeks, and no later than 12 weeks, after surgery. Patients will receive a maximum of 8 cycles of treatment with the combination of drugs and then receive panitumumab alone for a maximum of 12 cycles.
On treatment visits, patients will also have tests and procedures done. As part of the study, patients will provide archival tumor tissue and sample of tissue removed from surgery for K-ras testing. Patients will also be given the option of allowing the collected tissue for research (biomarker) studies and banking for future studies.
Read the detailed description
Emerging data suggests that KRAS mutation is a strong predictor for resistance to EGFR antagonist therapy. In the KRAS wild-type cohort, the addition of EGFR antagonists to chemotherapy has been shown to improve RR and PFS. Improved response rate to neoadjuvant chemotherapy would be expected to improve surgical outcomes for patients with CRCLM. We therefore wish to test the hypothesis that the combination of FOLFOX/FOLFIRI and panitumumab, given perioperatively to patients with wild-type KRAS CRCLM will improve outcome, compared to historical control, in optimally resectable patients. As this patient population remains at high risk for recurrence post-chemotherapy, we also wish to explore the tolerability and efficacy of continued panitumumab monotherapy for an additional 6 months.
As opposed to most clinical trials for advanced colorectal cancer where the majority are treated with palliative intent, patients in this trial will all be treated aggressively with curative intent at the outset. There is also the additional benefit of assessment of tumor tissue after treatment with a biologic agent.
- Conditions
- Colorectal Cancer, Liver Metastases
- Being tested
- Panitumumab, Oxaliplatin, 5-FU
- Keywords
- colorectal cancer, liver metastases, panitumumab, FOLFOX, Colorectal cancer with liver metastases
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Panitumumab, Oxaliplatin, 5-FUDrug
- Panitumumab 6 mg / kg, given over 60 minutes
- Oxaliplatin 85 mg / m2 combined with leucovorin 400 mg / m2, given over 2 hours OR
- Irinotecan 180 mg / m2 , given over 90 minutes, concurrent with leucovorin 400 mg / m2, given over 90 minutes
- 5FU 400 mg / m2, by bolus infusion
- 5FU 2400 mg / m2, given over 46 hours
| Study group | Role | What they receive |
|---|---|---|
| Folfox/Folfiri, Panitumumab | Experimental | Eligible patients will recieved chemotherapy/panitumumab for 2 months (4 cycles) pre-operatively and 4 months post-operatively, plus a further 6 months of pantimumab post-chemotherapy Receives: Drug: Panitumumab, Oxaliplatin, 5-FU |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the 2 year disease-free survival rate in patients with resectable colorectal liver metastases treated with FOLFOX/FOLFIRI + panitumumab for 2 months pre-operatively and 4 months post-operatively, followed by panitumumab alone for 6 months.
Measured: 2-years post-therapy
Secondary outcomes (6)
To evaluate the objective response rate (ORR) to preoperative FOLFOX/FOLFIRI plus panitumumab (by RECIST criteria) in patients with wild type KRAS.
Measured: until relapse
To evaluate the pathologic complete response rate.
Measured: until relapse
To determine overall survival and toxicity.
Measured: until death
To explore correlative biomarkers of clinical response (EGFR, PTEN, MET, BRAF and PI3KCA).
Measured: pre/post surgery
To explore for correlation between available tissue from biopsy, primary tumor and metastatic lesion with regards to aforementioned pathologic biomarkers.
Measured: pre/post surgery
To determine the incidence of hepatocellular damage (fibrosis, steatosis) in normal liver tissue induced by preoperative chemotherapy.
Measured: pre-surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2010 (estimated)
- Study startAug 2010
- Primary completionJun 2013
- Study completionJun 2013
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 University Health Network, TorontoThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stephen Welch, MD, Study chair, London Regional Cancer CenterSean Cleary, MD, Principal investigator, Toronto General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01260415
- Sponsor's protocol ID
- PMH DDP - CRCLM1
- Status last verified
- May 2019
- First submitted
- 13 Dec 2010
- Last updated
- 14 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Perioperative Chemotherapy Plus Panitumumab in Patients With Colorectal Cancer Liver Metastases
- ClinicalTrials.gov ID
- NCT01260415
- Acronym / sponsor ID
- PMH DDP - CRCLM1
- Conditions
- Colorectal Cancer, Liver Metastases
- Keywords
- colorectal cancer, liver metastases, panitumumab, FOLFOX, Colorectal cancer with liver metastases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- Aug 2010 (actual)
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 15 Dec 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.
This is a phase II study to assess whether treatment with chemotherapy drugs FOLFOX (5-Fluorouracil (5FU), Oxaliplatin (Eloxatin) and Leucovorin (Folinic Acid)) or FOLFIRI (5-Fluorouracil (5FU), Irinotecan (Camptosar) and Leucovorin (Folinic Acid))and panitumumab before and after surgery can improve outcome in patients with liver metastases (the cancer has spread to other parts of the body such as the liver) that are resectable (can be surgically removed), from colorectal cancer that have a non mutant (wild-type) K-ras gene.
FOLFOX/FOLFIRI is an intravenous (given by vein) chemotherapy combination that is approved for colorectal cancer while panitumumab is also an intravenous drug and have been approved for treatment of refractory (not responding treatment) metastatic colorectal cancer whose cancers have the K-ras gene. These drugs are not approved for the treatment of colorectal cancer liver metastases (CRCLM) who can have surgery.
Patients will receive FOLFOX/FOLFIRI and panitumumab for four 2-week cycles before surgery. Surgery will be done no sooner than 4 weeks and no later than 8 weeks, after completion of the fourth cycle of chemotherapy.
If the liver metastases after the chemotherapy and surgery decreases or stops growing, then chemotherapy will be given after surgery. Treatments will start no sooner than 4 weeks, and no later than 12 weeks, after surgery. Patients will receive a maximum of 8 cycles of treatment with the combination of drugs and then receive panitumumab alone for a maximum of 12 cycles.
On treatment visits, patients will also have tests and procedures done. As part of the study, patients will provide archival tumor tissue and sample of tissue removed from surgery for K-ras testing. Patients will also be given the option of allowing the collected tissue for research (biomarker) studies and banking for future studies.
Detailed description
Emerging data suggests that KRAS mutation is a strong predictor for resistance to EGFR antagonist therapy. In the KRAS wild-type cohort, the addition of EGFR antagonists to chemotherapy has been shown to improve RR and PFS. Improved response rate to neoadjuvant chemotherapy would be expected to improve surgical outcomes for patients with CRCLM. We therefore wish to test the hypothesis that the combination of FOLFOX/FOLFIRI and panitumumab, given perioperatively to patients with wild-type KRAS CRCLM will improve outcome, compared to historical control, in optimally resectable patients. As this patient population remains at high risk for recurrence post-chemotherapy, we also wish to explore the tolerability and efficacy of continued panitumumab monotherapy for an additional 6 months.
As opposed to most clinical trials for advanced colorectal cancer where the majority are treated with palliative intent, patients in this trial will all be treated aggressively with curative intent at the outset. There is also the additional benefit of assessment of tumor tissue after treatment with a biologic agent.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Folfox/Folfiri, Panitumumab | Experimental | Drug: Panitumumab, Oxaliplatin, 5-FUEligible patients will recieved chemotherapy/panitumumab for 2 months (4 cycles) pre-operatively and 4 months post-operatively, plus a further 6 months of pantimumab post-chemotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients must have histologically or cytologically confirmed colorectal cancer with available tissue to test for K-RAS mutation. Biopsy is required if no archived tissue is available. K-RAS mutation status must be confirmed prior to registration. Only patients with K-RAS wild-type cancers are eligible.
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan.
- Patients must have resectable hepatic colorectal metastases.
- Patients may have synchronous unresected primary disease upon registration. Primary must be resectable, either at same laparotomy or at separate laparotomy from liver resection.
- Age >18 years.
Key exclusion criteria (12 listed)
- Patients must have had no previous systemic treatment in the adjuvant or metastatic setting within 6 months of registration.
- Patients may not have had prior treatment with an EGFR antagonist.
- Patients may not have a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid malignancies curatively treated with no evidence of disease for ≥ 5 years.
- Patients may not have extrahepatic metastatic disease. Patients who have had prior surgical resection for hepatic metastases or extrahepatic disease (eg. pulmonary metastases) are also excluded from this study.
- Patients may not have pre-existing chronic hepatic disease (eg. cirrhosis, chronic active hepatitis B or C)
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, Oxaliplatin, 5-FU* Panitumumab 6 mg / kg, given over 60 minutes * Oxaliplatin 85 mg / m2 combined with leucovorin 400 mg / m2, given over 2 hours OR * Irinotecan 180 mg / m2 , given over 90 minutes, concurrent with leucovorin 400 mg / m2, given over 90 minutes * 5FU 400 mg / m2, by bolus infusion * 5FU 2400 mg / m2, given over 46 hours | Drug | Folfox/Folfiri, Panitumumab |
Primary outcome
To determine the 2 year disease-free survival rate in patients with resectable colorectal liver metastases treated with FOLFOX/FOLFIRI + panitumumab for 2 months pre-operatively and 4 months post-operatively, followed by panitumumab alone for 6 months.
Time frame: 2-years post-therapy
6 secondary outcomes
To evaluate the objective response rate (ORR) to preoperative FOLFOX/FOLFIRI plus panitumumab (by RECIST criteria) in patients with wild type KRAS.
Time frame: until relapse
To evaluate the pathologic complete response rate.
Time frame: until relapse
To determine overall survival and toxicity.
Time frame: until death
To explore correlative biomarkers of clinical response (EGFR, PTEN, MET, BRAF and PI3KCA).
Time frame: pre/post surgery
To explore for correlation between available tissue from biopsy, primary tumor and metastatic lesion with regards to aforementioned pathologic biomarkers.
Time frame: pre/post surgery
To determine the incidence of hepatocellular damage (fibrosis, steatosis) in normal liver tissue induced by preoperative chemotherapy.
Time frame: pre-surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2019.
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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.
Stephen Welch, MD study chair
London Regional Cancer Center
Sean Cleary, MD principal investigator
Toronto General Hospital
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, Oxaliplatin, 5-FU in people with Colorectal Cancer and Liver Metastases, run by University Health Network, Toronto at 4 sites in Canada.
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 11 inclusion and 12 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 14 May 2019. 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 Canada. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the 2 year disease-free survival rate in patients with resectable colorectal liver metastases treated with FOLFOX/FOLFIRI + panitumumab for 2 months pre-operatively and 4 months post-operatively, followed by panitumumab alone for 6 months. (time frame: 2-years post-therapy). 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 14 May 2019.