A Study of Dulanermin Administered in Combination With Camptosar®/Erbitux® Chemotherapy or FOLFIRI (With or Without Bevacizumab) in Subjects With Previously Treated Metastatic Colorectal Cancer

Sponsor

Genentech, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00671372

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

4.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will assess the safety and pharmacokinetics of adding dulanermin to Camptosar®/Erbitux® or the FOLFIRI regimen (Camptosar®, 5-FU, and leucovorin) plus bevacizumab (only for Cohort 6 subjects who have not received prior bevacizumab therapy).

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: FOLFIRI regimen Drug: bevacizumab Drug: cetuximab Drug: dulanermin Drug: irinotecan	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

42 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of Multiple Doses of Dulanermin Administered Intravenously in Combination With Camptosar®/Erbitux® Chemotherapy or the Folfiri Regimen With or Without Bevacizumab in Subjects With Previously Treated Metastatic Colorectal Cancer

Study Start Date :

Jul 1, 2006

Actual Primary Completion Date :

Mar 1, 2012

Actual Study Completion Date :

Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohorts 1-5	Drug: cetuximab Intravenous repeating dose Drug: dulanermin Intravenous repeating dose Drug: irinotecan Intravenous repeating dose
Experimental: Cohorts 6, 6A, 7, 7A	Drug: FOLFIRI regimen Intravenous repeating dose Drug: bevacizumab Intravenous repeating dose (for Cohort 6 subjects not previously treated with bevacizumab) Drug: dulanermin Intravenous repeating dose

Arm

Intervention/Treatment

Experimental: Cohorts 1-5

Drug: cetuximab

Intravenous repeating dose

Drug: dulanermin

Intravenous repeating dose

Drug: irinotecan

Intravenous repeating dose

Experimental: Cohorts 6, 6A, 7, 7A

Drug: FOLFIRI regimen

Intravenous repeating dose

Drug: bevacizumab

Intravenous repeating dose (for Cohort 6 subjects not previously treated with bevacizumab)

Drug: dulanermin

Intravenous repeating dose

Outcome Measures

Primary Outcome Measures

The safety and tolerability of dulanermin administered in combination with Camptosar and Erbitux [Length of study]
The safety and tolerability of dulanermin administered in combination with FOLFIRI (with or without Bevacizumab) [Length of study]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed Informed Consent Form
Age >= 18 years
Histologically confirmed CRC with evidence of metastases and measurable tumor lesion(s)
Progression of disease following, or intolerance to, treatment with 5-fluorouracil-based therapy
Progression of disease during or within =< 6 months following the last dose of a prior first-line treatment with a fluoropyrimidine and oxaliplatin-based chemotherapy plus bevacizumab for metastatic disease
Use of an effective means of contraception for women of childbearing potential and men with partners of childbearing potential (use per institutional standard)
Life expectancy of > 3 months
Willingness and capability to be accessible for study follow-up

Exclusion Criteria:

Prior radiotherapy to a measurable, metastatic lesion(s) to be used to measure response
Radiation therapy to a peripheral lesion within 14 days prior to Day 1; Radiation therapy to a thoracic, abdominal or pelvic field within 28 days prior to Day 1
Chemotherapy, hormonal therapy, or immunology within 4 weeks prior to Day 1
Previous exposure to DR4-targeted therapy or DR5-targeted therapy
Evidence of clinically detectable ascites on Day
Other invasive malignancies within 5 years prior to Day 1 (other than basal cell carcinoma of the skin or in situ carcinoma of the cervix)
History or evidence upon physical examination of CNS disease
Active infection requiring parenteral antibiotics on Day 1
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study and fine needle aspirations within 7 days prior to Day 1
Pregnancy or lactation
Serious nonhealing wound, ulcer, or bone fracture
Current or recent participation in another experimental drug study
Clinically significant cardiovascular disease
History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk from treatment complications
Cohort 5 only: Subjects who have a Kras mutation will be excluded from enrollment
The following exclusion criteria apply only to subjects who have received prior bevacizumab and are enrolled in Cohort 6: four or more prior doses of bevacizumab therapy, inadequately controlled hypertension, history of hypertensive crisis or hypertensive encephalopathy, history of arterial thromboembolic event 6 months prior to Day 1, proteinuria, history of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	Los Angeles	California	United States	90095
2	Redlands	California	United States	92374
3	San Francisco	California	United States	94115
4	Fort Myers	Florida	United States	33916
5	Harvey	Illinois	United States	60426
6	Buffalo	New York	United States	14263
7	Durham	North Carolina	United States	27710
8	Hershey	Pennsylvania	United States	17033
9	Nashville	Tennessee	United States	37203
10	Tacoma	Washington	United States	98405