Capecitabine Plus Aflibercept as Maintenance Therapy Following Capecitabine Plus Oxaliplatin Plus Aflibercept in Patients With Metastatic Colorectal Cancer (Drop and Go)
Primary Purpose
Colorectal Cancer Metastatic
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Capecitabine
Aflibercept AVE0005
Oxaliplatin SR96669
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer Metastatic
Eligibility Criteria
Inclusion criteria:
- Age ≥18 years of both sexes
- Histologically confirmed mCRC
- Unresectable metastatic colorectal cancer. (Patient with resectable metastases (liver or lung) is not eligible.)
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2
- A life expectancy of >3 months
- At least one measurable lesion according to RECIST (version 1.1)
- No prior chemotherapy for advanced disease. Patients with prior (neo)adjuvant chemotherapy completed more than 6 months prior metastatic relapse are eligible (adjuvant does not include the chemotherapy after resection of distant metastases).
- Adequate hematological profile (absolute neutrophil count >1.5 x 109/L, platelet count >100 x 109/L, hemoglobin >9 g/dL)
- Adequate liver function: AST, ALT <3.0 x ULN (or <5 xULN in the case of liver function abnormalities due to underlying liver metastases); Alkaline Phosphatase <3 x ULN (or <5 x ULN if due to underlying liver metastases); Total bilirubin <1.5 x ULN
- Serum creatinine < 1.5 x upper limit of normal (ULN). If creatinine 1.0-1.5 x ULN, creatinine clearance will be calculated according to the CKD-EPI formula and creatinine clearance < 60 mL/min will exclude the patient
- Proteinuria <2+ functions
- Signed patient informed consent before beginning specific protocol procedures
- Ability to comply with protocol requirements
Exclusion criteria:
- Less than 4 weeks from prior radiotherapy to the time of inclusion (less than 2 weeks in case of palliative RT on single bone lesion only)
- Less than 4 weeks following major surgery to the time of inclusion or until the surgical wound is fully healed whichever came later (48 hours in case of minor surgical procedure or until wound full healing observed)
- Treatment with any other investigational product within 28 days prior to inclusion
- Other prior neoplasm. Adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or any other cancer from which the patient has been disease-free for > 5 years are allowed
- History of brain metastases (unless adequately controlled, i.e. previously irradiated, inactive brain metastases not requiring active treatment like steroids or antiepileptics), active seizure disorder, uncontrolled spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease
- Any of the following within 6 months prior to inclusion: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, NYHA class III or IV congestive heart failure, stroke or transient ischemic attack
- Any of the following within 3 months prior to inclusion: Grade 3-4 gastrointestinal bleeding/hemorrhage (unless due to resected tumor), treatment resistant peptic ulcer disease, erosive oesophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism or other uncontrolled thromboembolic event
- Occurrence of deep vein thrombosis within 4 weeks, prior to inclusion
- Any severe acute or chronic medical condition, which could impair the ability of the patient to participate in the study or interfere with interpretation of study results. Known Acquired immunodeficiency syndrome (AIDS-related illnesses) or known human immunodeficiency virus (HIV) disease requiring antiretroviral treatment
- Pregnant or breast-feeding woman. Positive pregnancy test (serum or urine β-HCG) for women of reproductive potential
- Patient with reproductive potential (M/F) who do not agree to use accepted and effective method of contraception during the study treatment period and for at least 6 months after the completion of the study treatment. The definition of "effective method of contraception" will be based on the Investigator's judgment
- Patient on anticoagulant therapy with warfarin (coumarin-derivative). Anticoagulation with low molecular weight heparin (LWMH) is permitted
- Symptomatic peripheral sensory neuropathy grade ≥ 2 (NCI-CTCAE v4.03)
- Inability to take oral medications
- Prior history of chronic enteropathy, inflammatory enteropathy, chronic diarrhea, malabsorption syndrome, unresolved bowel obstruction/sub-obstruction, surgery more extensive than hemicolectomy, extensive small intestine resection with chronic diarrhea.
- History of hypersensitivity to fluoropyrimidines or known/suspected allergy to any agent given during the study or to any excipient to study drugs
- Known dihydropyrimidine dehydrogenase deficiency
- Any contraindication to administer oxaliplatin, 5-FU, folinic acid or capecitabine as per package insert of each drug
- Uncontrolled hypertension (defined as BP > 140/90 mmHg or systolic BP >160 mmHg when diastolic BP < 90 mmHg, on at least 2 repeated determinations on separate days, or upon clinical judgment) within 3 months prior to study inclusion
- Evidence of clinically significant bleeding diathesis or underlying coagulopathy (e.g. INR>1.5 without vitamine K antagonist therapy), non-healing wound
- History of hypersensitivity to Aflibercept (in case of prior administration for an indication other than cancer, i.e. ophthalmic indication)
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Aflibercept
Arm Description
Intravenous (IV) infusion on Day 1 every 3 weeks, followed by CAPOX (capecitabine by oral administration on Day 1 to Day 14 and oxaliplatin intravenous (IV) infusion on Day 1 every 3 weeks) for the induction treatment period (6 cycles) after which the patient may enter the maintenance period during which the treatment is Aflibercept + Capecitabine
Outcomes
Primary Outcome Measures
Progression Free Survival rate at 10 months (PFS@10m)
Secondary Outcome Measures
Progression Free Survival (PFS) - Time
Overall Survival (OS) - Time
Assessment of Objective Response Rate (ORR)
Total Score as a measure of Health Related Quality of Life
Number of participants with adverse events
Full Information
NCT ID
NCT02085005
First Posted
March 10, 2014
Last Updated
November 17, 2014
Sponsor
Sanofi
Collaborators
Regeneron Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT02085005
Brief Title
Capecitabine Plus Aflibercept as Maintenance Therapy Following Capecitabine Plus Oxaliplatin Plus Aflibercept in Patients With Metastatic Colorectal Cancer
Acronym
Drop and Go
Official Title
Phase II Study of First-line Capecitabine Plus Oxaliplatin Plus Aflibercept for 6 Cycles Followed by Capecitabine Plus Aflibercept as Maintenance Therapy in Patients With Metastatic Colorectal Cancer: DROP and GO Trial
Study Type
Interventional
2. Study Status
Record Verification Date
November 2014
Overall Recruitment Status
Withdrawn
Study Start Date
March 2014 (undefined)
Primary Completion Date
August 2016 (Anticipated)
Study Completion Date
August 2016 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
Collaborators
Regeneron Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Primary Objective:
Efficacy: To assess the progression-free survival rate at 10 months in patients on maintenance therapy with capecitabine plus aflibercept.
Secondary Objectives:
To evaluate:
Efficacy: Progression Free Survival (PFS)
Efficacy: Overall Survival (OS)
Efficacy: Objective Response Rate (ORR) as per Response Evaluation Criteria In Solid Tumors (RECIST version 1.1) criteria
Health related Quality of Life (HRQL): EORTC QLQ-C30 scores and EQ5D-3L
Safety
Exploratory Objective:
To collect blood and tumor samples to perform investigations for potential biomarker testing.
Detailed Description
Total study duration for a participant can be up to 28 months.
This trial is being conducted in countries where the INN designation for the study molecule is "aflibercept" and this term is therefore used throughout the synopsis. In the US, the US proper name is "ziv-aflibercept".
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer Metastatic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Aflibercept
Arm Type
Experimental
Arm Description
Intravenous (IV) infusion on Day 1 every 3 weeks, followed by CAPOX (capecitabine by oral administration on Day 1 to Day 14 and oxaliplatin intravenous (IV) infusion on Day 1 every 3 weeks) for the induction treatment period (6 cycles) after which the patient may enter the maintenance period during which the treatment is Aflibercept + Capecitabine
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
Pharmaceutical form:tablet Route of administration: oral
Intervention Type
Drug
Intervention Name(s)
Aflibercept AVE0005
Intervention Description
Pharmaceutical form:concentrate for infusion Route of administration: intravenous
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin SR96669
Intervention Description
Pharmaceutical form:solution for infusion Route of administration: intravenous
Primary Outcome Measure Information:
Title
Progression Free Survival rate at 10 months (PFS@10m)
Time Frame
every 9 weeks, up to 28 months
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS) - Time
Time Frame
every 9 weeks, up to 28 months
Title
Overall Survival (OS) - Time
Time Frame
every 9 weeks, up to 28 months
Title
Assessment of Objective Response Rate (ORR)
Time Frame
every 9 weeks, up to 28 months
Title
Total Score as a measure of Health Related Quality of Life
Time Frame
every 3 weeks, up to end of treatment
Title
Number of participants with adverse events
Time Frame
up to 30 days after last treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Age ≥18 years of both sexes
Histologically confirmed mCRC
Unresectable metastatic colorectal cancer. (Patient with resectable metastases (liver or lung) is not eligible.)
Eastern Cooperative Oncology Group (ECOG) performance status ≤2
A life expectancy of >3 months
At least one measurable lesion according to RECIST (version 1.1)
No prior chemotherapy for advanced disease. Patients with prior (neo)adjuvant chemotherapy completed more than 6 months prior metastatic relapse are eligible (adjuvant does not include the chemotherapy after resection of distant metastases).
Adequate hematological profile (absolute neutrophil count >1.5 x 109/L, platelet count >100 x 109/L, hemoglobin >9 g/dL)
Adequate liver function: AST, ALT <3.0 x ULN (or <5 xULN in the case of liver function abnormalities due to underlying liver metastases); Alkaline Phosphatase <3 x ULN (or <5 x ULN if due to underlying liver metastases); Total bilirubin <1.5 x ULN
Serum creatinine < 1.5 x upper limit of normal (ULN). If creatinine 1.0-1.5 x ULN, creatinine clearance will be calculated according to the CKD-EPI formula and creatinine clearance < 60 mL/min will exclude the patient
Proteinuria <2+ functions
Signed patient informed consent before beginning specific protocol procedures
Ability to comply with protocol requirements
Exclusion criteria:
Less than 4 weeks from prior radiotherapy to the time of inclusion (less than 2 weeks in case of palliative RT on single bone lesion only)
Less than 4 weeks following major surgery to the time of inclusion or until the surgical wound is fully healed whichever came later (48 hours in case of minor surgical procedure or until wound full healing observed)
Treatment with any other investigational product within 28 days prior to inclusion
Other prior neoplasm. Adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or any other cancer from which the patient has been disease-free for > 5 years are allowed
History of brain metastases (unless adequately controlled, i.e. previously irradiated, inactive brain metastases not requiring active treatment like steroids or antiepileptics), active seizure disorder, uncontrolled spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease
Any of the following within 6 months prior to inclusion: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, NYHA class III or IV congestive heart failure, stroke or transient ischemic attack
Any of the following within 3 months prior to inclusion: Grade 3-4 gastrointestinal bleeding/hemorrhage (unless due to resected tumor), treatment resistant peptic ulcer disease, erosive oesophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism or other uncontrolled thromboembolic event
Occurrence of deep vein thrombosis within 4 weeks, prior to inclusion
Any severe acute or chronic medical condition, which could impair the ability of the patient to participate in the study or interfere with interpretation of study results. Known Acquired immunodeficiency syndrome (AIDS-related illnesses) or known human immunodeficiency virus (HIV) disease requiring antiretroviral treatment
Pregnant or breast-feeding woman. Positive pregnancy test (serum or urine β-HCG) for women of reproductive potential
Patient with reproductive potential (M/F) who do not agree to use accepted and effective method of contraception during the study treatment period and for at least 6 months after the completion of the study treatment. The definition of "effective method of contraception" will be based on the Investigator's judgment
Patient on anticoagulant therapy with warfarin (coumarin-derivative). Anticoagulation with low molecular weight heparin (LWMH) is permitted
Symptomatic peripheral sensory neuropathy grade ≥ 2 (NCI-CTCAE v4.03)
Inability to take oral medications
Prior history of chronic enteropathy, inflammatory enteropathy, chronic diarrhea, malabsorption syndrome, unresolved bowel obstruction/sub-obstruction, surgery more extensive than hemicolectomy, extensive small intestine resection with chronic diarrhea.
History of hypersensitivity to fluoropyrimidines or known/suspected allergy to any agent given during the study or to any excipient to study drugs
Known dihydropyrimidine dehydrogenase deficiency
Any contraindication to administer oxaliplatin, 5-FU, folinic acid or capecitabine as per package insert of each drug
Uncontrolled hypertension (defined as BP > 140/90 mmHg or systolic BP >160 mmHg when diastolic BP < 90 mmHg, on at least 2 repeated determinations on separate days, or upon clinical judgment) within 3 months prior to study inclusion
Evidence of clinically significant bleeding diathesis or underlying coagulopathy (e.g. INR>1.5 without vitamine K antagonist therapy), non-healing wound
History of hypersensitivity to Aflibercept (in case of prior administration for an indication other than cancer, i.e. ophthalmic indication)
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
Capecitabine Plus Aflibercept as Maintenance Therapy Following Capecitabine Plus Oxaliplatin Plus Aflibercept in Patients With Metastatic Colorectal Cancer
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