Colorectal CancerPhase 2PEPCOLNCT01375816
Liposome-encapsulated Irinotecan Hydrochloride PEP02 or Irinotecan Hydrochloride, Leucovorin Calcium, and Fluorouracil as Second-Line Therapy in Treating Patients With Metastatic Colorectal Cancer
A Phase 2 study testing FOLFIRI 1-Bevacizumab, fluorouracil and irinotecan hydrochloride in people with Colorectal Cancer, run by GERCOR - Multidisciplinary Oncology Cooperative Group at 1 site in France.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as liposome-encapsulated irinotecan hydrochloride PEP02, irinotecan hydrochloride, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- FOLFIRI 1-Bevacizumab, fluorouracil and irinotecan hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteFrance
- Study dates
- May 2011to Dec 2014
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS
- Histologically proven adenocarcinoma of colon or rectum
- Metastatic disease, exclusive of bone metastasis
- Not suitable for complete carcinological surgical resection
- Patients regardless KRAS status (wild type or mutated) or previous anti EGFR treatment or not.
- Measurable lesion (greater than 1 cm) as assessed by CT scan or MRI according to RECIST criteria (version 1.1)
- Must have received prior oxaliplatin-based chemotherapy for metastatic disease
- No symptomatic ascites or pleural effusion not evacuated prior to study entry
- No history or evidence of CNS metastasis
PATIENT CHARACTERISTICS:
- WHO or ECOG performance status 0-2
- Absolute neutrophil count greater than 1500 per mm3
- Platelet count greater than 100 000 per microL
- Hemoglobin greater than 9 g per dL (may be transfused to maintain or exceed this level)
- INR less or equal than 1.5. aPTT less than 1.5 ULN (exemption:patients on full anticoagulation due to VTE must have an in-range INR.
- Serum creatinine less than 150 micromol per L
- Calculated creatinine clearance greater than 30 mL per min
- Total bilirubin less than 1.5 times upper limit of normal
- Proteinuria less than 2 plus (dipstick urinalysis) or less than 1 g per 24 hours.
- Negative serum pregnancy test
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No severe arterial thromboembolic events within the past 6 months, including myocardial infarction and stroke
- No baseline diarrhea greater than grade 1
- No total or partial bowel obstruction
- No uncontrolled hypercalcemia
- No uncontrolled hypertension, or history of hypertensive crisis, or hypertensive encephalopathy
- No other prior or concurrent malignancy, except adequately treated in situ carcinoma of the uterine cervix, basal cell or squamous cell carcinoma of the skin, or cancer in complete remission for more than 5 years
- No other serious and uncontrolled non-malignant disease
- Major surgery or traumatic injury within the last 28 days.
- No known allergy to any excipients of study drugs
- Must be registered in a national health care system (CMU included)
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Prior anti-EGFR therapy allowed
- No prior irinotecan hydrochloride
- No concurrent agents known to have anticancer activity
- No concurrent radiotherapy
- No participation in another clinical trial with any investigational drug or treatments concurrently or within the past 30 days
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Phase II Study of PEP02 or Irinotecan in Combination With Leucovorin and 5-Fluorouracil in Second Line Therapy of Metastatic Colorectal Cancer
RATIONALE: Drugs used in chemotherapy, such as liposome-encapsulated irinotecan hydrochloride PEP02, irinotecan hydrochloride, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving liposome-encapsulated irinotecan hydrochloride PEP02 together with leucovorin calcium and fluorouracil is more effective than giving irinotecan hydrochloride together with leucovorin calcium and fluorouracil as second-line therapy in treating patients with metastatic colorectal cancer.
PURPOSE: This randomized phase II trial is studying liposome-encapsulated irinotecan hydrochloride PEP02 given together with leucovorin calcium and fluorouracil to see how well it works compared with giving irinotecan hydrochloride together with leucovorin calcium and fluorouracil as second-line therapy in treating patients with metastatic colorectal cancer.
Read the detailed description
OBJECTIVES:
Primary
- To evaluate the objective response rates (complete response and partial response) in patients with metastatic colorectal cancer treated with liposome-encapsulated irinotecan hydrochloride PEP02, leucovorin calcium, and fluorouracil (FUPEP) Versus irinotecan hydrochloride, leucovorin calcium, and fluorouracil (FOLFIRI 1) or leucovorin calcium, fluorouracil, and irinotecan hydrochloride-modified (FOLFIRI 3-modified).
Secondary
- To determine the safety of these regimens in these patients.
- To determine progression-free survival of these patients.
- To determine overall survival of these patients.
- To assess the quality of life of these patients.
- To assess the correlation of UGT1A family polymorphism and the toxicity of liposome-encapsulated irinotecan hydrochloride PEP02 or irinotecan hydrochloride.
OUTLINE: This is a multicenter study. Patients are stratified, in terms of prognosis, according to treatment center, prognostic score (ECOG performance status [PS] 0 and normal LDH value vs ECOG PS > 1 and/or LDH > 1 times upper limit of normal), and time to progression after first-line therapy (≥ 9 months vs < 9 months). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients are assigned to either the FOLFIRI 1 or Modified FOLFIRI 3 treatment groups according to the investigator's discretion in combination with bevacizumab
- FOLFIRI 1 in combination with bevacizumab: Patients receive bevacizumab over 30-90 minutes,irinotecan hydrochloride over 1 hour and leucovorin calcium IV over 2 hours on day 1 and a bolus of fluorouracil followed by fluorouracil IV over 46 hours beginning on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity
- Modified FOLFIRI 3 in combination with bevacizumab: Patients receive bevacizumab,irinotecan hydrochloride, leucovorin calcium, and fluorouracil as in FOLFIRI 1. Patients also receive irinotecan hydrochloride IV over 1 hour on day 3. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
- Arm II (FUPEP)in combination with bevacizumab: Patients receive bevacizumab over 30-90 minutes liposome-encapsulated irinotecan hydrochloride PEP02 IV over 60-90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically for pharmacogenetic analysis of UGT1A family polymorphisms. Quality of life is assessed by using a generic scale EQ-5D and the QLQ-C30 questionnaire at baseline and after courses 4 and 8.
After completion of study treatment, patients are followed up at day 30 and then every 2-3 months thereafter.
- Conditions
- Colorectal Cancer
- Being tested
- FOLFIRI 1-Bevacizumab, fluorouracil, irinotecan hydrochloride, leucovorin calcium, liposome-encapsulated irinotecan hydrochloride PEP02
- Keywords
- adenocarcinoma of the colon, recurrent colon cancer, stage IV colon cancer, adenocarcinoma of the rectum, recurrent 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.
FOLFIRI 1-BevacizumabDrug
fluorouracilDrug
liposome-encapsulated irinotecan hydrochloride PEP02Drug
BevacizumabDrug
| Study group | Role | What they receive |
|---|---|---|
| FOLFIRI 1 or m FOLFIRI3-Bevacizumab | Active comparator | FOLFIRI 1-Bevacizumab:
Day 1 H0 : Bevacizumab 5 mg/kg, 30-90 min infusion H+1: Irinotecan 180 mg/m² in 250 ml NaCl 0.9%, 1h infusion Folinic Acid 400 mg/m² (l + d racemic form, or l form 200 mg/m²) over 2h H + 3: 5-FU bolus 400 mg/m², 15 min infusion H + 3.5: 5-FU continuous infusion 2400 mg/m² 46-h infusion End of cycle: day 14
modified FOLFIRI3-Bevacizumab H0 :Bevacizumab 5 mg/kg, 30-90 min infusion H+1:Irinotecan 90 mg/m² in 250 ml NaCl 0.9%, 1h infusion H+1: Folinic Acid 400 mg/m² (l + d racemic form, or l form 200 mg/m²) 2-h infusion H + 3: 5-FU continuous infusion 2400 mg/m² 46-h infusion Day 3 (H+49) H0 Irinotecan 90 mg/m² in 250 ml NaCl 0.9%, 1h infusion End of cycle: day 14 Receives: Drug: FOLFIRI 1-Bevacizumab; Drug: fluorouracil; Drug: irinotecan hydrochloride; Drug: leucovorin calcium; Drug: Bevacizumab |
| FUPEP-Bevacizumab | Experimental | Day 1 H0 :Bevacizumab 5 mg/kg, 30-90 min infusion H +1 :PEP02 80 mg/m² , 1h30 infusion. The infusion time could be reduced to 1h from cycle 2 if no acute infusion reaction has occured in cycle 1.
H +1 : Folinic Acid 400 mg/m² (l + d racemic form, or l form 200 mg/m²) , 2-h infusion H +3 : 5-FU continuous infusion 2400 mg/m² 46-h infusion End of cycle: day 14 Receives: Drug: fluorouracil; Drug: leucovorin calcium; Drug: liposome-encapsulated irinotecan hydrochloride PEP02; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor response
Assessment of tumor response at 2 month after randomization by RECIST 1.1
Measured: at 2 months
Secondary outcomes (5)
Safety
assessment of adverse events and toxicity according NCI CTC v4.0
Measured: before each 2-weeks cycles
Progression-free survival
Measured: the time from the date of randomization to the date of progressive disease (RECIST criteria) or death (any cause)
Overall survival
Measured: from the date of randomization to the date of patient death, due to any cause, or to the last date the patient was known to be alive
Quality of life
Quality of life will be assessed by using a generic scale EQ-5D and the QLQ-C30 questionnaire
Measured: at baseline, cycle 4, and cycle 8
Correlation of UGT1A family polymorphism and the toxicity of liposome-encapsulated irinotecan hydrochloride PEP02 or irinotecan hydrochloride
Measured: at baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2011 (estimated)
- Study startMay 2011
- Primary completionJun 2014
- Study completionDec 2014
Why it stopped: efficacy interim analysis as per protocol
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.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- GERCOR - Multidisciplinary Oncology Cooperative Group
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Frederique Maindrault-Goebel, MD, Principal investigator, Hopital Saint Antoine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01375816
- Sponsor's protocol ID
- CDR0000701454
- Other IDs
- FRE-GERCOR-PEPCOL-C10-1, EU-21115, EUDRACT-2010-020468-39, PHARMAENGINE-FRE-GERCOR-PEPCOL
- Acronym
- PEPCOL
- Status last verified
- Nov 2013
- First submitted
- 16 Jun 2011
- Last updated
- 4 Jun 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Study of PEP02 or Irinotecan in Combination With Leucovorin and 5-Fluorouracil in Second Line Therapy of Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT01375816
- Acronym / sponsor ID
- PEPCOL / CDR0000701454
- Conditions
- Colorectal Cancer
- Keywords
- adenocarcinoma of the colon, recurrent colon cancer, stage IV colon cancer, adenocarcinoma of the rectum, recurrent rectal cancer, stage IV rectal cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: efficacy interim analysis as per protocol
- Enrolment
- 55 participants (actual)
- Lead sponsor
- GERCOR - Multidisciplinary Oncology Cooperative GroupUniversity, hospital or other
- Study start
- May 2011
- Primary completion
- Jun 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 17 Jun 2011 (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: Drugs used in chemotherapy, such as liposome-encapsulated irinotecan hydrochloride PEP02, irinotecan hydrochloride, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving liposome-encapsulated irinotecan hydrochloride PEP02 together with leucovorin calcium and fluorouracil is more effective than giving irinotecan hydrochloride together with leucovorin calcium and fluorouracil as second-line therapy in treating patients with metastatic colorectal cancer.
PURPOSE: This randomized phase II trial is studying liposome-encapsulated irinotecan hydrochloride PEP02 given together with leucovorin calcium and fluorouracil to see how well it works compared with giving irinotecan hydrochloride together with leucovorin calcium and fluorouracil as second-line therapy in treating patients with metastatic colorectal cancer.
Detailed description
OBJECTIVES:
Primary
- To evaluate the objective response rates (complete response and partial response) in patients with metastatic colorectal cancer treated with liposome-encapsulated irinotecan hydrochloride PEP02, leucovorin calcium, and fluorouracil (FUPEP) Versus irinotecan hydrochloride, leucovorin calcium, and fluorouracil (FOLFIRI 1) or leucovorin calcium, fluorouracil, and irinotecan hydrochloride-modified (FOLFIRI 3-modified).
Secondary
- To determine the safety of these regimens in these patients.
- To determine progression-free survival of these patients.
- To determine overall survival of these patients.
- To assess the quality of life of these patients.
- To assess the correlation of UGT1A family polymorphism and the toxicity of liposome-encapsulated irinotecan hydrochloride PEP02 or irinotecan hydrochloride.
OUTLINE: This is a multicenter study. Patients are stratified, in terms of prognosis, according to treatment center, prognostic score (ECOG performance status [PS] 0 and normal LDH value vs ECOG PS > 1 and/or LDH > 1 times upper limit of normal), and time to progression after first-line therapy (≥ 9 months vs < 9 months). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients are assigned to either the FOLFIRI 1 or Modified FOLFIRI 3 treatment groups according to the investigator's discretion in combination with bevacizumab
- FOLFIRI 1 in combination with bevacizumab: Patients receive bevacizumab over 30-90 minutes,irinotecan hydrochloride over 1 hour and leucovorin calcium IV over 2 hours on day 1 and a bolus of fluorouracil followed by fluorouracil IV over 46 hours beginning on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity
- Modified FOLFIRI 3 in combination with bevacizumab: Patients receive bevacizumab,irinotecan hydrochloride, leucovorin calcium, and fluorouracil as in FOLFIRI 1. Patients also receive irinotecan hydrochloride IV over 1 hour on day 3. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
- Arm II (FUPEP)in combination with bevacizumab: Patients receive bevacizumab over 30-90 minutes liposome-encapsulated irinotecan hydrochloride PEP02 IV over 60-90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically for pharmacogenetic analysis of UGT1A family polymorphisms. Quality of life is assessed by using a generic scale EQ-5D and the QLQ-C30 questionnaire at baseline and after courses 4 and 8.
After completion of study treatment, patients are followed up at day 30 and then every 2-3 months thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FOLFIRI 1 or m FOLFIRI3-Bevacizumab | Active comparator | Drug: FOLFIRI 1-Bevacizumab, Drug: fluorouracil, Drug: irinotecan hydrochloride, Drug: leucovorin calcium, Drug: BevacizumabFOLFIRI 1-Bevacizumab: Day 1 H0 : Bevacizumab 5 mg/kg, 30-90 min infusion H+1: Irinotecan 180 mg/m² in 250 ml NaCl 0.9%, 1h infusion Folinic Acid 400 mg/m² (l + d racemic form, or l form 200 mg/m²) over 2h H + 3: 5-FU bolus 400 mg/m², 15 min infusion H + 3.5: 5-FU continuous infusion 2400 mg/m² 46-h infusion End of cycle: day 14 modified FOLFIRI3-Bevacizumab H0 :Bevacizumab 5 mg/kg, 30-90 min infusion H+1:Irinotecan 90 mg/m² in 250 ml NaCl 0.9%, 1h infusion H+1: Folinic Acid 400 mg/m² (l + d racemic form, or l form 200 mg/m²) 2-h infusion H + 3: 5-FU continuous infusion 2400 mg/m² 46-h infusion Day 3 (H+49) H0 Irinotecan 90 mg/m² in 250 ml NaCl 0.9%, 1h infusion End of cycle: day 14 |
| FUPEP-Bevacizumab | Experimental | Drug: fluorouracil, Drug: leucovorin calcium, Drug: liposome-encapsulated irinotecan hydrochloride PEP02, Drug: BevacizumabDay 1 H0 :Bevacizumab 5 mg/kg, 30-90 min infusion H +1 :PEP02 80 mg/m² , 1h30 infusion. The infusion time could be reduced to 1h from cycle 2 if no acute infusion reaction has occured in cycle 1. H +1 : Folinic Acid 400 mg/m² (l + d racemic form, or l form 200 mg/m²) , 2-h infusion H +3 : 5-FU continuous infusion 2400 mg/m² 46-h infusion End of cycle: day 14 |
Who may qualify
- Ages
- 18 to 75 years
- 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 |
|---|---|---|
| FOLFIRI 1-Bevacizumab | Drug | FOLFIRI 1 or m FOLFIRI3-Bevacizumab |
| fluorouracil | Drug | FOLFIRI 1 or m FOLFIRI3-Bevacizumab, FUPEP-Bevacizumab |
| irinotecan hydrochloride | Drug | FOLFIRI 1 or m FOLFIRI3-Bevacizumab |
| leucovorin calcium | Drug | FOLFIRI 1 or m FOLFIRI3-Bevacizumab, FUPEP-Bevacizumab |
| liposome-encapsulated irinotecan hydrochloride PEP02 | Drug | FUPEP-Bevacizumab |
| Bevacizumab | Drug | FOLFIRI 1 or m FOLFIRI3-Bevacizumab, FUPEP-Bevacizumab |
Primary outcome
Tumor response
Time frame: at 2 months
Assessment of tumor response at 2 month after randomization by RECIST 1.1
5 secondary outcomes
Safety
Time frame: before each 2-weeks cycles
Progression-free survival
Time frame: the time from the date of randomization to the date of progressive disease (RECIST criteria) or death (any cause)
Overall survival
Time frame: from the date of randomization to the date of patient death, due to any cause, or to the last date the patient was known to be alive
Quality of life
Time frame: at baseline, cycle 4, and cycle 8
Correlation of UGT1A family polymorphism and the toxicity of liposome-encapsulated irinotecan hydrochloride PEP02 or irinotecan hydrochloride
Time frame: at baseline
Results and safety
The study was stopped early (reason given: efficacy interim analysis as per protocol). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2015.
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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.
Frederique Maindrault-Goebel, MD principal investigator
Hopital Saint Antoine
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 FOLFIRI 1-Bevacizumab, fluorouracil and irinotecan hydrochloride in people with Colorectal Cancer, run by GERCOR - Multidisciplinary Oncology Cooperative Group at 1 site in France.
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: stopped early, as of the sponsor's last update on 4 Jun 2015. 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 France. 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 was stopped early (reason given: efficacy interim analysis as per protocol). Results are not available in the source record.
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?
Tumor response (time frame: at 2 months). 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 4 Jun 2015.