An Open-Label, Randomized Phase 2 Study of ABT-869 in Combination With mFOLFOX6 (Oxaliplatin, 5-Fluorouracil, and Folinic Acid) Versus Bevacizumab in Combination With mFOLFOX6 as Second-line Treatment of Subjects With Advanced Colorectal Cancer

• Conditions: Advanced colorectal cancer; MedDRA version: 13.1Level: PTClassification code 10010030Term: Colorectal cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 13.1Level: PTClassification code 10052358Term: Colorectal cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 13.1Level: PTClassification code 10061451Term: Colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 13.1Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 13.1Level: PTClassification code 10010035Term: Colorectal cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2007-007081-38-BE
• Lead Sponsor: Abbott GmbH & Co KG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-01-13
• Last Update Posted: 15 July 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 135

Inclusion Criteria

1. The subject must be = 18 years of age.
2. The subject must be diagnosed with adenocarcinoma of the colon or rectum.
3. The subject must have metastatic disease or locally recurrent disease that is not
amenable to surgical resection with curative intent.
4. The subject must have received one prior chemotherapy regimen containing
irinotecan or a fluoropyrimidine for locally recurrent or metastatic colorectal
cancer. The subject has experienced progressive disease during or following the
prior chemotherapy treatment.
5. The subject may have received prior adjuvant treatment for colorectal cancer.
6. The subject has measurable disease, defined as at least 1 unidimensionally
measurable lesion on a CT scan as defined by RECIST version 1.1 (for subjects in
the randomized portion only).
7. The subject has an Eastern Cooperative Oncology Group (ECOG) performance
score of 0-1.
8. The subject must have adequate bone marrow, renal and hepatic function as
follows:
a. Bone Marrow: absolute neutrophil count (ANC) = 1,500/mm3
(1.5 × 109/L); platelets = 100,000/mm3 (100 × 109/L); hemoglobin
= 9.0 g/dL (1.4 mmol/L);
b. Renal function: serum creatinine = 2.0 mg/dL (0.177 mmol/L);
c. Hepatic function: AST and ALT = 1.5 × ULN unless liver metastases are present, then AST and ALT = 5.0 × ULN; bilirubin = 1.5 mg/dL (0.026 mmol/L).
9. The subject must have PTT = 1.5 × ULN and INR = 1.5.
10. Female subjects of childbearing potential must have a negative urine pregnancy
test within 7 days prior to initiation of treatment, must be surgically sterile and/or
post menopausal women must be amenorrheic for at least 12 months to be
considered of non-childbearing potential. Female subjects of childbearing
potential and male subjects must agree to use adequate contraception (one of the following listed below) prior to study entry, for the duration of study participation
and up to two months following completion of therapy.
? Total abstinence from sexual intercourse (minimum one complete menstrual
cycle);
? A vasectomized partner;
? Hormonal contraceptives (oral, parenteral or transdermal) for at least
3 months prior to study drug administration;
? Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal
ring with spermicidal jellies or cream).
11. The subject is capable of understanding and complying with parameters as
outlined in the protocol and able to sign and date the informed consent, approved
by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB),
prior to the initiation of any screening or study-specific procedures.
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. The subject has received more than one prior therapy in the metastatic setting.
Lead-in Cohort only: The subject may have received more than one prior therapy
in the metastatic setting.
2. The subject has received cytotoxic chemotherapy (i.e. alkylating agents,
microtubule inhibitors, anti-metabolites) within 21 days prior to Study Day 1.
3. The subject has received non-cytotoxic, anti-cancer therapy within 21 days or
within a period defined by 5 half lives whichever is shorter, prior to study drug
administration. Anti-cancer therapies include, but are not limited to:
investigational agents (any agent not approved for use in humans),
immunotherapy, anti-cancer traditional Chinese medicine/herbal remedies,
hormonal, targeted agents (i.e., erlotinib, imatinib, sorafenib) or biologic
therapy.
4. The subject has not recovered to less than or equal to Grade 1 clinically significant
adverse effects/toxicities of the previous therapy.
5. The subject has received prior treatment with a tyrosine kinase inhibitor targeting
VEGF or PDGF.
6. The subject has received prior treatment for colorectal cancer with oxaliplatin in
the metastatic setting. Lead-in cohort only: Prior treatment with oxaliplatin will
be allowed provided that any neuropathy as a result of the oxaliplatin treatment has
resolved to less than or equal to Grade 1.
7. The subject has had major surgery within 28 days of Study Day 1.
8. The subject has had radiotherapy within 14 days of Study Day 1.
9. The subject has symptomatic or untreated brain or meningeal metastases. CT
scans are not required to rule out brain or meningeal metastases unless there is a
clinical suspicion of central nervous system disease. Subjects with treated brain
metastases that are radiographically or clinically stable for at least 4 weeks after
therapy and have no evidence of cavitation or hemorrhage in the brain lesion are
eligible providing that they are asymptomatic and do not require corticosteroids
(must have discontinued steroids at least 1 week prior to study drug
administration).
10. The subject has a history of hypersensitivity to recombinant murine monoclonal
antibodies, oxaliplatin or other platinum-containing compounds, 5-fluorouracil, or
folinic acid.
11. The subject has proteinuria CTC grade > 1 at baseline as measured by a urine
dipstick and confirmed by a 24-hour urine collection.
12. The subject is receiving therapeutic anticoagulation therapy. Low dose
anticoagulation (e.g., low dose warfarin) for catheter prophylaxis will be
permitted.
13. The subject has a history of, or currently exhibits, clinically significant cancer
related events of bleeding (e.g., gross hemoptysis defined as bright red blood of at
least ½ teaspoon or 2.5 mL per episode within three months prior to Study Day 1
unless definitively treated with surgery or radiation) or the subject has a recent
history of (within four weeks of Study Day 1) or currently exhibits other clinically
significant signs of bleeding.
14. The subject currently exhibits symptomatic or persistent, uncontrolled
hypertension defined as diastolic blood pressure (BP) > 90 mmHg; or systolic
blood pressure (BP) > 140 mmHg. Subjects may be re-screened if blood pressure
is shown to be controlled with or without intervention.
15. The subject has a history of myocardial infarction, stroke, or transient ischemic
attack (TIA) within six months of Study Day 1.
16. The subject has a history of abdominal fist

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess if the addition of oral ABT-869 to mFOLFOX6 (5-fluorouracil, folinic acid, and oxaliplatin) can prolong progression-free survival (PFS) compared to bevacizumab plus mFOLFOX6 as second-line treatment in subjects with advanced colorectal cancer. ;Secondary Objective: To evaluate overall survival and additional efficacy endpoints (listed in Section 8.1.6 of the study protocol), as well as the safety and tolerability of the combination. <br><br>The tertiary objectives are to evaluate quality of life and performance status.;Primary end point(s): The primary endpoint of the study is progression free survival. The secondary endpoints of the study will be overall survival, 12-month survival rate, time to disease progression, objective response rate, best response rate, best percent change in tumor size, duration of response, as well as the safety and tolerability of the combination. The tertiary endpoints are quality of life and performance status.