A Phase 2, Open Label, Multicenter, Randomized Trial Comparing Tivozanib in Combination with mFOLFOX6 with Bevacizumab in Combination with mFOLFOX6 in Stage IV Metastatic Corectal Cancer (mCRC) Subjects
- Conditions
- Bowel cancerMetastatic colorectal cancer (CRC)10017991
- Registration Number
- NL-OMON39372
- Lead Sponsor
- Astellas Pharma
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 17
1. The subject is male or female, aged 18 years or older.
2. The subject has histologically or cytologically confirmed mCRC for which bevacizumab/ mFOLFOX6 chemotherapy regimen would be the appropriate treatment per the investigator.
3. The subject has at least one measurable lesion by RECIST Version 1.1. A lesion that has received prior radiotherapy may only be counted as
a target lesion if it has progressed since radiotherapy as determined by
PI or radiologist assessment.
4. The subject has had no prior systemic chemotherapy for advanced colorectal cancer; no fluorouracil containing adjuvant therapy in previous 6 months.
5. The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Female subject must be either:
-post-menopausal (defined as at least 1 year without any mensus) prior to Screening, or
- premenarchal prior to Screening, or
- documented surgically sterile or status post hysterectomy (at least 1 month prior to Screening), or
- if of childbearing potential, must have a negative serum or urine pregnancy test at Screening and must be using highly effective contraception
7. Male subject and their female spouses/partners who are of childbearing potential must be using highly effective contraception consisting of two forms of birth control (one of which must be a barrier method) starting Screening and continue throughout the study period and for 90 days after final study drug administration.
8) Female subject must not be breastfeeding at Screening or during the study period and for 90 days after final study drug administration.
9) Female subject must not donate ova starting at Screening and throughout the study period and for 90 days after final study drug administration.
10) Male subject must not donate sperm starting at Screening and throughout the study period and for 90 days after final study drug administration.
11) Subject agrees not to participate in another investigational study while on study treatment.
The subject has;
1.- had any prior VEGF-directed therapy including VEGF antibody or any other agent or investigational agent targeting the VEGF pathway.
2.- has primary CNS malignancies or CNS metastases; subjects with previously treated brain metastases will be allowed if the brain metastasis have been stable without steroid treatment for at least 3 months following prior treatment (radiotherapy or surgery).
3.- has any of the following hematologic abnormalities: • Hemoglobin >= 9.0 g/dL (90 g/L, 5.5854 mmol/L) • ANC <2000 per mm3 • Platelet count <100,000 per mm3 • PT or PTT > 1.5 X ULN
4.-has any of the following serum chemistry abnormalities: • Total bilirubin > 1.5 X ULN (or > 2.5 X ULN for subjects with Gilbert*s syndrome) • AST or ALT > 2.5 X ULN (or > 5 X ULN for subjects with liver metastasis) • Alkaline phosphatase > 2.5 X ULN (or > 5 X ULN for subjects with liver or bone metastasis) • Serum albumin < 2.0 g/dL • Creatinine > 1.5 X ULN (or calculated creatinine clearance < 60mL/min/1.73m2) • Proteinuria > 2+ by urine dipstick; protein greater than 2+ must have 24-hour urine collection that is less than 2 gm/24hr
5. The subject has significant cardiovascular disease
6. The subject has significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug.
7. The subject has a non-healing wound, bone fracture, or skin ulcer.
8. The subject has inadequate recovery from any prior surgical procedure or major surgical procedure within 4 weeks prior to administration of first dose of study drug, or anticipation of major surgical procedure during the course of the study.
9. The subject has history of significant gastrointestinal (GI) toxicity, diarrhea, or stomatitis within the last 6 weeks.
10. The subject has an active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal condition with increased risk of perforation.
11. The subject has history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug.
12. The subject has a serious/active infection or infection requiring antibiotics.
13. The subject has significant bleeding disorders within 6 months prior to administration of first dose of study drug.
14. The subject has currently active second primary malignancy, including hematologic malignancies, other than non-melanoma skin cancers, non-metastatic prostate cancer and in situ cervical cancer and ductal or lobular carcinoma in situ of the breast. Subject is not considered to have currently active malignancy if they have completed anti-cancer therapy and have been disease free for > 5 years.
15. The subject has history of allergic reactions, or intolerance, attributed to compounds of similar chemical or biologic composition to 5-fluorouracil, history of Grade 3 hypersensitivity to oxaliplatin, history of allergic reaction to folic acid.
The subject has a;
17.- known history of genetic or acquired immune suppression disease including HIV; subjects on immune suppressive therapy for organ transplant.
18. - an inability to swallow pills, malabsorption syndrome or gastrointestinal disease that would severely affect the absorption of tivozanib, major resection of the stomach or small bowel, or gastric bypass.
19.- uncontrolled neuro-psychiatric disorder or altered mental status precluding
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary efficacy analysis: median Progression Free Survival (PFS). PFS is<br /><br>defined as the time from randomization until radiological<br /><br>progression assessed by the investigator or death due to any cause. PFS will be<br /><br>compared between two treatment arms.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary efficacy analyses: objective response rate (ORR), progression free<br /><br>survival (PFS) based on independent radiological review (IRR), overall survival<br /><br>(OS), time to treatment failure (TTF), and the duration of the response (DoR)<br /><br>will be compared between two treatment arms.</p><br>