A Randomized, Double-Blind, Phase II Trial of CT-322 (BMS-844203) plus Irinotecan,5-FU and Leucovorin (FOLFIRI) versus Bevacizumab plus FOLFIRI as Second-LineTreatment for Metastatic Colorectal Cancer

Phase 1

Conditions: Second-Line Treatment for Metastatic Colorectal Cancer
MedDRA version: 9.1Level: LLTClassification code 10052362Term: Metastatic colorectal cancer

Registration Number: EUCTR2008-006561-89-FR

Lead Sponsor: Bristol Myers Squibb International Corporation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 135

Inclusion Criteria

1) Signed Written Informed Consent

2) Target Population
a) Histologically or cytologically confirmed, unresectable, metastatic adenocarcinoma of the colon or rectum that has progressed following first-line treatment which included each of the following agents:
i) A fluoropyrimidine (5-FU or capecitabine)
ii) Oxaliplatin (Subjects who are intolerant to oxaliplatin, defined as any toxicity
preventing treatment with oxaliplatin, are permitted if disease progression has
been documented following discontinuation of oxaliplatin)
iii) Bevacizumab (last dose of bevacizumab must be < 8 weeks from the start of
study therapy).
b) Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) = 1
c) Resolution of all prior therapy-related toxicities to = Grade 1 or baseline
d) Measurable disease as defined by RECIST criteria (at least 1 target lesion
= 20 mm by conventional techniques, or = 10 mm by spiral CT)
i) If the only measurable disease is located in a previously radiated area, lesions
must be documented as new lesions since the completion of radiotherapy.
3) Age and Sex
a) Men and women of = 18 years of age.
b) Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study (and for up to 4 weeks
after the last dose of investigational product) in such a manner that the risk of
pregnancy is minimized.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) Sex and Reproductive Status
a) WOCBP who are unwilling or unable to use an acceptable method to avoid
pregnancy for the entire study [and for up to 4 weeks after the last dose of
investigational product].
b) Women who are pregnant or breastfeeding
c) Women with a positive pregnancy test on enrollment or prior to investigational
product administration.
d) Sexually active fertile men not using effective birth control if their partners are
WOCBP.
2) Target Disease Exceptions
a) Known Central Nervous System (CNS) metastases.
3) Medical History and Concurrent Diseases
a) Excessive risk of bleeding such as history of clinically significant bleeding
diathesis or coagulopathy including platelet function disorder or acquired
bleeding disorder within 12 months.
b) Thrombotic or embolic cerebrovascular accident including transient ischemic
attacks within the past 12 months.
c) Uncontrolled hypertension (defined as systolic blood pressure > 150 mmHg or
diastolic > 90 mmHg, measured repeatedly at = 2 visits despite adequate
treatment with = 2 different antihypertensive drugs).
d) Clinically significant cardiovascular disease, including (but not limited to) the
following:
i) Myocardial infarction within the past 6 months
ii) Unstable angina
iii) New York Heart Association class II-IV congestive heart failure
iv) Serious cardiac arrhythmia (eg, ventricular arrhythmia, high-grade atrioventricular-block), not controlled by medication or requiring medication which might interfere with regularity of study treatment.
v) Left ventricular ejection fraction (LVEF) below institutional lower limit of
normal (LLN) as measured by 2-dimensional echocardiogram (ECHO) or cardiac MUGA scan.
e) History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months.
f) Serious non-healing wound, active peptic ulcer, non-healing bone fracture, or
bleeding skin metastases.
g) Active infection requiring IV antibiotics.
h) Glomerulonephritis or other protein-wasting glomerulopathy.
i) Gilbert’s disease.
j) Any concurrent malignancy other than non-melanoma skin cancer or carcinoma
in-situ of the cervix.
k) Dementia, altered mental status, or any psychiatric condition that would prohibit
the understanding or rendering of informed consent.
l) A serious uncontrolled medical disorder that, in the opinion of the investigator,
would impair the ability of the subject to receive study therapy.
4) Physical and Laboratory Test Findings
a) Hematology:
i) Hemoglobin < 9.0 g/dL, Absolute Neutrophil Count < 1500 /mm3, Platelets
< 100,000 /mm3
b) Chemistry:
i) Serum creatinine > 1.5 times the institutional upper limit of normal (ULN)
ii) Serum total bilirubin > 1.5 times ULN
iii) ALT or AST > 2.5 times ULN (> 5 times ULN for subjects with documented
liver metastases).
iv) Serum amylase and lipase > 1.5 times ULN.
c) Known UGT1A1*28 allele homozygosity.
5) Allergies and Adverse Drug Reactions
a) Known hypersensitivity to any of the study drugs or excipients.
6) Prohibited Treatments and/or Therapies
a) Any prior treatment with irinotecan, including treatment in the adjuvant setting.
b) Any prior treatment with VEGF or VEGFR inhibitors, with the exception of
bevacizumab.
c) Radiotherapy or major surgery within 4 weeks prior to study treatment.
d) Any investigational drug within 4 weeks prior to study treatment.
e) Use of full dose anticoagulants or thrombolytics.
f) St. John’s Wort should be discontinued at least 2 weeks prior to the first cycle

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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