Adenocarcinoma of the ColonPhase 2NCT02046538
Phase II Study of Zaltrap and Chemotherapy for Advanced Resectable Colorectal Cancer
A Phase 2 study testing Leucovorin, Oxaliplatin and 5-FU in people with Adenocarcinoma of the Colon and Adenocarcinoma of the Rectum, run by Weill Medical College of Cornell University at 1 site in United States.
Trial summary
The purpose of this study is to establish the safety of Zaltrap in patients who undergo pre-operative chemotherapy with Zaltrap. The investigators hypothesize that Zaltrap my impact colorectal cancer growth and metastasis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenocarcinoma of the Colon, Adenocarcinoma of the Rectum
- What is being tested?
- Leucovorin, Oxaliplatin and 5-FU
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2014to Feb 2018
- 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 pathologically confirmed adenocarcinoma of the colon or rectum.
- In patients with liver-limited metastatic colorectal cancer, a curative approach is indicated following evaluation by hepatobiliary surgeon as part of multidisciplinary management. Select patients requiring two stage procedure are also eligible following evaluation by hepatobiliary surgeon as part of multidisciplinary management.
- In patients with rectal cancer, primary tumor that is clinically T3-4 or N + (evaluation by colorectal surgery is required as part of multidisciplinary approach).
- No prior chemotherapy for metastatic disease is allowed for patients with CRC-liver mets. (adjuvant FOLFOX is permitted)
- No prior chemotherapy for proximal rectal cancer is allowed
- ECOG Performance status ≤ 2.
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- Age >18 years old.
- Patients must have adequate bone marrow, kidney, and liver function as assessed by laboratory parameters.
- WBC ≥ 3,000/uL
- Total Bilirubin ≤ 1.5 x upper limits of normal
- AST (SGOT) ≤ 3 x upper limits of normal
- ALT (SGPT) ≤ 3 x upper limits of normal
- Hemoglobin ≥ 9.0 g/dl (without transfusion within 7 d)
- ANC ≥ 1500 /ml
- Platelets ≥100 K/ml (without transfusion)
- Calculated CrCL > 50 ml/min
- Ability to understand and the willingness to sign a written informed consent document.
- 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 and for the duration of study participation.
Who cannot join
- Patients with untreated CNS metastases.
- Significant medical co-morbidity that would preclude safe administration of cytotoxic therapy, including but not limited to:
- Cardiovascular disease
- Unstable angina
- Myocardial infarction/ CABG < 3 months prior to study initiation
- Untreated coronary artery disease
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- NYHA class III or IV heart failure
- Ongoing serious infection
- Bacteremia or sepsis requiring intravenous antibiotics
- HIV with AIDS defining illness
- Inadequate oral nutritional intake: Requirement for daily intravenous fluids or total parenteral nutrition.
- Neurological: Stroke ≤ 6 months
- Psychiatric illness/social situations that would limit compliance with study requirement
- Patients may not receive another investigational agent.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Ziv-aflibercept.
- Pregnant (positive pregnancy test) and lactating women are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown.
- Major surgical procedure ≤ 4 weeks from starting therapy.
- Grade 3-4 hemorrhage, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, or diverticulits ≤ 3 months from starting therapy.
- Patients with known DPD deficiency
- Patients with known Gilbert's syndrome
- Patients with ≥ 2g/24 hour urine protein. If urine protein on random UA is ≤ 300 mg/dl, a 24 hour urine protein is not required.
- Symptomatic peripheral sensory neuropathy grade ≥ 2.
- Other malignancy within the last 5 years from study entry, except for basal /squamous cell skin cancer, in situ cervical cancer, or non-metastatic prostate cancer.
Trial locations and contacts
1 site in 1 country.
United States1 site
Weill Cornell Medical College
New York, New York, 10065
About this study
Official title: Phase II Study of Preoperative Chemotherapy With Ziv-aflibercept (Zaltrap) Followed by Postoperative Chemotherapy With or Without Ziv-aflibercept (Zaltrap) in Patients With Advanced Resectable Colorectal Cancer
The purpose of this study is to establish the safety of Zaltrap in patients who undergo pre-operative chemotherapy with Zaltrap. The investigators hypothesize that Zaltrap my impact colorectal cancer growth and metastasis.
Read the detailed description
Eligible patients will receive 3 months of chemotherapy consisting of either FOLFOX or FOLFIRI (in the case of liver limited CRC) or FOLFOX (in the case of rectal cancer). The FOLFOX regimen consists of Oxaliplatin, Leucovorin, and 5-FU. The FOLFIRI regimen consists of Irinotecan, Leucovorin, and 5-FU. Zaltrap will be administered with chemotherapy every 2 weeks for the first 5 out of 6 planned treatment cycles. After a standard 3-4 week recovery period (i.e. 5-6 week's from the last Zaltrap dose), patients will undergo standard resection. At the time of resection, the tumor will be collected for biomarker discovery.
Following resection, patients will be randomly assigned (1:1) to receive chemotherapy with or without zaltrap for 3 additional months. Patients assigned to Zaltrap may continue zaltrap (without chemotherapy) until disease recurrence or up to an additional 15 months. Patients will have research blood draws periodically both in the preoperative and postoperative period.
The investigators plan to demonstrate that pre-operative chemotherapy with Zaltrap is not associated with any safety signals that would preclude further drug development in this patient population. The investigators also plan to perform correlative studies to identify potential biomarkers for Zaltrap activity.
The investigators hypothesize that antiangiogenic therapy may specifically target the micrometastatis niche of patients with liver limited metastatic colorectal cancer to significantly increase the chance of cure for these patients.
- Being tested
- Leucovorin, Oxaliplatin, 5-FU, Irinotecan
- Medical subject headings
- Colonic Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LeucovorinDrug
Also called Wellcovorin
400 mg/m2 IV over two hours (or administered concurrently with oxaliplatin or irinotecan, depending on the assigned regimen)
OxaliplatinDrug
Also called Eloxatin
85 mg/m2 IV over two hours
5-FUDrug
Also called Adrucil, fluorouracil
400 mg/m2 IV bolus, then 2400 mg/m2 continuous IV infusion over 46-48 hours
IrinotecanDrug
Also called Camptosar
180 mg/m2 IV over 90 minutes
| Study group | Role | What they receive |
|---|---|---|
| Postoperative Chemo WITH Zaltrap | Experimental | Subjects will receive 3 months of chemotherapy consisting of either FOLFOX (oxaliplatin, leucovorin, 5-FU) or FOLFIRI (Irinotecan, leucovorin, 5-FU) in the case of liver limited CRC, or FOLFOX (in the case of rectal cancer). Zaltrap will be administered with chemotherapy every 2 weeks for the first 5 out of 6 planned treatment cycles. After a standard 3-4 week recovery period (i.e. 5-6 weeks from the last Zaltrap dose), patients will undergo standard resection. At the time of resection, the tumor will be collected for biomarker discovery.
Following resection, patients will receive chemotherapy with zaltrap for 3 additional months. Patients may continue zaltrap (without chemotherapy) until disease recurrence or up to an additional 15 months. Receives: Drug: Leucovorin; Drug: Oxaliplatin; Drug: 5-FU; Drug: Irinotecan |
| Postoperative chemo WITHOUT zaltrap | Active comparator | Subjects will receive 3 months of chemotherapy consisting of either FOLFOX (oxaliplatin, leucovorin, 5-FU) or FOLFIRI (Irinotecan, leucovorin, 5-FU) in the case of liver limited CRC, or FOLFOX (in the case of rectal cancer). Zaltrap will be administered with chemotherapy every 2 weeks for the first 5 out of 6 planned treatment cycles. After a standard 3-4 week recovery period (i.e. 5-6 weeks from the last Zaltrap dose), patients will undergo standard resection. At the time of resection, the tumor will be collected for biomarker discovery.
Following resection, patients will receive chemotherapy (without zaltrap) for 3 additional months. Receives: Drug: Leucovorin; Drug: Oxaliplatin; Drug: 5-FU; Drug: Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of adverse events experienced
Capture the number of adverse events experienced by advanced resectable colorectal cancer subjects treated with pre-operative chemotherapy and Zaltrap
Measured: Approximately 24 months per patient
Number of subjects who demonstrate a response to pre-operative chemotherapy and zaltrap
Capture the number of subjects who demonstrate an improvement (response) in colorectal cancer status after being treated with pre-operative chemotherapy and zaltrap.
Measured: Approximately 24 months per patient
Secondary outcomes (1)
Survival duration without disease progression
Calculate rate of progression-free survival for subjects following treatment chemotherapy and Zaltrap
Measured: 2 years per patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2014 (estimated)
- Study startFeb 2014
- Primary completionFeb 2016 (estimated)
- Study completionFeb 2018 (estimated)
Why it stopped: Investigator terminated due to funding issues
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adenocarcinoma of the ColonStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi
- Responsible party
- Sponsor
- Investigators
- Manish A. Shah, MD, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02046538
- Sponsor's protocol ID
- 1309014302
- Other IDs
- 2012-AFL-18
- Status last verified
- Jan 2017
- First submitted
- 23 Jan 2014
- Last updated
- 25 Jan 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Preoperative Chemotherapy With Ziv-aflibercept (Zaltrap) Followed by Postoperative Chemotherapy With or Without Ziv-aflibercept (Zaltrap) in Patients With Advanced Resectable Colorectal Cancer
- ClinicalTrials.gov ID
- NCT02046538
- Acronym / sponsor ID
- 1309014302
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Investigator terminated due to funding issues
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- Sanofi
- Study start
- Feb 2014
- Primary completion
- Feb 2016 (estimated)
- Study completion
- Feb 2018 (estimated)
- First posted
- 27 Jan 2014 (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.
The purpose of this study is to establish the safety of Zaltrap in patients who undergo pre-operative chemotherapy with Zaltrap. The investigators hypothesize that Zaltrap my impact colorectal cancer growth and metastasis.
Detailed description
Eligible patients will receive 3 months of chemotherapy consisting of either FOLFOX or FOLFIRI (in the case of liver limited CRC) or FOLFOX (in the case of rectal cancer). The FOLFOX regimen consists of Oxaliplatin, Leucovorin, and 5-FU. The FOLFIRI regimen consists of Irinotecan, Leucovorin, and 5-FU. Zaltrap will be administered with chemotherapy every 2 weeks for the first 5 out of 6 planned treatment cycles. After a standard 3-4 week recovery period (i.e. 5-6 week's from the last Zaltrap dose), patients will undergo standard resection. At the time of resection, the tumor will be collected for biomarker discovery.
Following resection, patients will be randomly assigned (1:1) to receive chemotherapy with or without zaltrap for 3 additional months. Patients assigned to Zaltrap may continue zaltrap (without chemotherapy) until disease recurrence or up to an additional 15 months. Patients will have research blood draws periodically both in the preoperative and postoperative period.
The investigators plan to demonstrate that pre-operative chemotherapy with Zaltrap is not associated with any safety signals that would preclude further drug development in this patient population. The investigators also plan to perform correlative studies to identify potential biomarkers for Zaltrap activity.
The investigators hypothesize that antiangiogenic therapy may specifically target the micrometastatis niche of patients with liver limited metastatic colorectal cancer to significantly increase the chance of cure for these patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Postoperative Chemo WITH Zaltrap | Experimental | Drug: Leucovorin, Drug: Oxaliplatin, Drug: 5-FU, Drug: IrinotecanSubjects will receive 3 months of chemotherapy consisting of either FOLFOX (oxaliplatin, leucovorin, 5-FU) or FOLFIRI (Irinotecan, leucovorin, 5-FU) in the case of liver limited CRC, or FOLFOX (in the case of rectal cancer). Zaltrap will be administered with chemotherapy every 2 weeks for the first 5 out of 6 planned treatment cycles. After a standard 3-4 week recovery period (i.e. 5-6 weeks from the last Zaltrap dose), patients will undergo standard resection. At the time of resection, the tumor will be collected for biomarker discovery. Following resection, patients will receive chemotherapy with zaltrap for 3 additional months. Patients may continue zaltrap (without chemotherapy) until disease recurrence or up to an additional 15 months. |
| Postoperative chemo WITHOUT zaltrap | Active comparator | Drug: Leucovorin, Drug: Oxaliplatin, Drug: 5-FU, Drug: IrinotecanSubjects will receive 3 months of chemotherapy consisting of either FOLFOX (oxaliplatin, leucovorin, 5-FU) or FOLFIRI (Irinotecan, leucovorin, 5-FU) in the case of liver limited CRC, or FOLFOX (in the case of rectal cancer). Zaltrap will be administered with chemotherapy every 2 weeks for the first 5 out of 6 planned treatment cycles. After a standard 3-4 week recovery period (i.e. 5-6 weeks from the last Zaltrap dose), patients will undergo standard resection. At the time of resection, the tumor will be collected for biomarker discovery. Following resection, patients will receive chemotherapy (without zaltrap) for 3 additional months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patients must have pathologically confirmed adenocarcinoma of the colon or rectum.
- In patients with liver-limited metastatic colorectal cancer, a curative approach is indicated following evaluation by hepatobiliary surgeon as part of multidisciplinary management. Select patients requiring two stage procedure are also eligible following evaluation by hepatobiliary surgeon as part of multidisciplinary management.
- In patients with rectal cancer, primary tumor that is clinically T3-4 or N + (evaluation by colorectal surgery is required as part of multidisciplinary approach).
- No prior chemotherapy for metastatic disease is allowed for patients with CRC-liver mets. (adjuvant FOLFOX is permitted)
- No prior chemotherapy for proximal rectal cancer is allowed
Key exclusion criteria (23 listed)
- Patients with untreated CNS metastases.
- Significant medical co-morbidity that would preclude safe administration of cytotoxic therapy, including but not limited to:
- Patients may not receive another investigational agent.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Ziv-aflibercept.
- Pregnant (positive pregnancy test) and lactating women are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown.
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 |
|---|---|---|
| LeucovorinAlso: Wellcovorin400 mg/m2 IV over two hours (or administered concurrently with oxaliplatin or irinotecan, depending on the assigned regimen) | Drug | Postoperative Chemo WITH Zaltrap, Postoperative chemo WITHOUT zaltrap |
| OxaliplatinAlso: Eloxatin85 mg/m2 IV over two hours | Drug | Postoperative Chemo WITH Zaltrap, Postoperative chemo WITHOUT zaltrap |
| 5-FUAlso: Adrucil, fluorouracil400 mg/m2 IV bolus, then 2400 mg/m2 continuous IV infusion over 46-48 hours | Drug | Postoperative Chemo WITH Zaltrap, Postoperative chemo WITHOUT zaltrap |
| IrinotecanAlso: Camptosar180 mg/m2 IV over 90 minutes | Drug | Postoperative Chemo WITH Zaltrap, Postoperative chemo WITHOUT zaltrap |
Primary outcome
Number of adverse events experienced
Time frame: Approximately 24 months per patient
Capture the number of adverse events experienced by advanced resectable colorectal cancer subjects treated with pre-operative chemotherapy and Zaltrap
Number of subjects who demonstrate a response to pre-operative chemotherapy and zaltrap
Time frame: Approximately 24 months per patient
Capture the number of subjects who demonstrate an improvement (response) in colorectal cancer status after being treated with pre-operative chemotherapy and zaltrap.
1 secondary outcome
Survival duration without disease progression
Time frame: 2 years per patient
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2017.
- 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.
Manish A. Shah, MD principal investigator
Weill Medical College of Cornell University
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 Leucovorin, Oxaliplatin and 5-FU in people with Adenocarcinoma of the Colon and Adenocarcinoma of the Rectum, run by Weill Medical College of Cornell University 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 18 inclusion and 23 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: withdrawn, as of the sponsor's last update on 25 Jan 2017. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Number of adverse events experienced (time frame: Approximately 24 months per patient). 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 25 Jan 2017.