Safety of AMG 706 Plus Panitumumab Plus Chemotherapy in the Treatment of Subjects With Metastatic Colorectal Cancer

Rectal Cancer Clinical Trial

Official title:

An Open-Label, Dose-Finding Study to Evaluate the Safety of AMG 706 Plus Panitumumab Plus Chemotherapy in the Treatment of Subjects With Metastatic Colorectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00101894
• Other study ID #: 20040205
• Status: Completed
• Phase: Phase 1
• First received: January 18, 2005
• Last updated: September 13, 2012
• Start date: December 2004
• Est. completion date: December 2011

Study information

• Verified date: September 2012
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to characterize the safety and tolerability of AMG 706 plus panitumumab when administered with either FOLFIRI or FOLFOX4 chemotherapy regimens. This is a Phase 1b clinical study.

Other known NCT identifiers

• NCT00107328

Recruitment information / eligibility

• Status: Completed
• Enrollment: 119
• Est. completion date: December 2011
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

For complete inclusion and exclusion criteria, please refer to the investigator. Inclusion Criteria

1. Competent to comprehend, sign, and date an Institutional Review Board (IRB) approved informed consent form

2. Diagnosis of metastatic colorectal adenocarcinoma (may have received 1 prior chemotherapy regimen for metastatic CRC)

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

4. Adequate hematological function

5. Adequate renal function

6. Adequate hepatic function

7. Life expectancy of greater than or equal to 3 months as documented by the investigator

Exclusion Criteria:

1. More than 1 prior chemotherapy regimen for metastatic CRC

2. Central nervous system (CNS) metastases

3. History of venous thrombosis

4. Myocardial infarction, cerebrovascular accident, transient ischemic attack, grade 2 or greater peripheral vascular disease, congestive heart failure, ongoing arrhythmias requiring medication, or unstable angina within 1 year before study enrollment

5. History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on screening chest computed tomograph (CT) scan

6. Average systolic blood pressure > 150mm Hg or average diastolic blood pressure of > 90mm Hg

7. Radiotherapy within 28 days of study enrollment or within 14 days of study enrollment for peripheral lesions

8. Prior AMG 706, oral inhibitors of AMG706, panitumumab, or another anti-EGFr monoclonal antibody (mAb) (e.g., cetuximab [Erbitux®] or EMD 72000)

9. Systemic chemotherapy within 28 days before study enrollment

10. Major surgery within 28 days or minor surgery within 7days of study enrollment

11. History of life threatening ventricular arrhythmia (eg, sustained ventricular tachycardia)

12. Female and male subjects of childbearing potential not using adequate contraceptive precautions

13. Participation in therapeutic clinical trials within 30 days before study enrollment

14. Not recovered from all previous therapies

15. Clinically significant open would, ulcer or fracture

16. Any co-morbid medical condition that would increase the risk of toxicity

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colon Cancer
• Colorectal Neoplasms
• Rectal Cancer

Intervention

Drug:
• FOLFOX-4
The FOLFOX-4 regimen will be administered every 2 weeks as follows: Day 1: oxaliplatin (ELOXATIN™) 85 mg/m2 IV infusion and leucovorin racemate 200 mg/m2 (or 100 mg/m2 l-LV) IV infusion given over 120 ± 10 minutes at the same time in separate bags using a Y-line, followed by 5-FU 400 mg/m2 IV bolus given over 2 to 4 minutes, followed by 5-FU 600 mg/m2 IV infusion as a 22-hour ± 2 hours continuous infusion Day 2: leucovorin racemate 200 mg/m2 (or 100 mg/m2 l-LV) IV infusion over 120 ± 10 minutes, followed by 5-FU 400 mg/m2 IV bolus given over 2 to 4 minutes, followed
• AMG 706
AMG 706 is a small organic molecule that has been shown in preclinical pharmacology studies to be a potent, oral, multi-kinase inhibitor with anti-angiogenic and anti-tumor activity achieved by selectively inhibiting all known VEGF receptors, PDGF receptor, and Kit.

Biological:
• Panitumumab (Part 1a only)
Panitumumab will be administered by IV infusion at a dose of 6 mg/kg on day 1 of each 2-week cycle.

Drug:
• FOLFIRI
Irinotecan will be administered over 90 minutes ± 15 minutes on day 1 of each 2-week cycle. Leucovorin will be administered over 2 hours ± 15 minutes during the irinotecan infusion but without mixing, immediately followed by a 5-FU bolus and a 5-FU 46-hour ± 2-hour continuous intravenous infusion.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1a - The incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicities		First 2 cycles	Yes
Primary	Part 1b - The incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicities		First 2 cycles	Yes
Primary	Part 2 - The overall objective tumor response rate (complete and partial response) in subjects treated with AMG 706 (at the dose determined in Part 1b), with either the FOLFIRI or FOLFOX-4 chemotherapy regimen		Every 8 weeks (+/- 7 days)	No
Secondary	Part 1a - The PK of irinotecan (and its active metabolite SN38) when administered as a part of the FOLFIRI regimen with panitumumab and AMG 706		Cycle 1 and 2 (Days 1, 2, 3)	No
Secondary	Part 1a - The PK of oxaliplatin when administered as a part of the FOLFOX-4 regimen with panitumumab and AMG 706		Cycle 1 and 2 (Day 1)	No
Secondary	Part 1a - The objective tumor response rate (complete and partial response) throughout the study		Every 6 to 8 weeks	No
Secondary	Part 1b - The incidence of adverse events and clinical laboratory abnormalities not defined as dose-limiting toxicities		Every visit	Yes
Secondary	Part 1b - The PK of AMG 706 when administered with either the FOLFIRI or FOLFOX-4 chemotherapy regimen		Cycle 2 (Day 1-2), Cycle 3 (Day 1)	No
Secondary	Part 1b - The PK of 5-FU when administered as a part of the FOLFIRI or FOLFOX-4 regimen with AMG 706		Cycle 1 and 2 (Day 3)	No
Secondary	Part 2 - Duration of response: (Calculated for only those subjects who respond)		Time from first objective tumor response (subsequently confirmed at least 4 weeks later) to objective disease progression or death.	No
Secondary	Part 2 - Time-to-progression		Time from first dose of investigational product to objective disease progression or death due to disease progression.	No
Secondary	Part 1b - The PK of irinotecan (and its active metabolite SN38) when administered as a part of the FOLFIRI regimen with AMG 706		Cycle 1 and 2 (Days 1, 2, 3)	No
Secondary	Part 1b- The PK of oxaliplatin when administered as a part of the FOLFOX-4 regimen with AMG 706		Cycle 1 and 2 (Day 1)	No
Secondary	Part 1b - The objective tumor response rate (complete and partial response) throughout the study		Every 8 weeks (+/- 7 days)	No
Secondary	Part 2 - Overall survival		Time from first dose of investigational product to death. Subjects who have not died while on study or are lost to follow-up will be censored at their last contact date. (Time on study plus 36 months of long term follow-up)	No
Secondary	Part 2 - The incidence of adverse events and clinical laboratory abnormalities		Every visit	Yes
Secondary	Part 2 - The PK of AMG 706 when administered with either the FOLFIRI or FOLFOX-4 chemotherapy regimen (at a subset of the study centers with the capabilities to draw, ship and process PK samples)		Cycles 2, 4, 7, and every 3 subsequent cycles (Day 1)	No
Secondary	Exploratory - Potential biomarker development based on assessment of blood cells, tumor cells, and urine and the proposed mechanism of action of study drugs, and response		Day 1 of cycles 1 and 2, and within 7 days of a radiographic assessment	No
Secondary	Exploratory - The effects of genetic variation in drug metabolism genes, cancer genes, and drug target genes on subject response to investigational products (separate informed consent)		Day 1 of cycles 1 and 2, and within 7 days of a radiographic assessment	No
Secondary	Part 2 - Progression-free survival time		Time from first dose of investigational product to objective disease progression or death, subjects who have not progressed or died while on study will be censored at their last evaluable assessment date.	No
Secondary	Part 2 - Incidence of subjects undergoing resection of metastases for curative intent		As needed	Yes
Secondary	Part 1a - The incidence of adverse events and clinical laboratory abnormalities not defined as dose-limiting toxicities		Every visit	Yes
Secondary	Part 1a - The PK of AMG 706 when administered with panitumumab and either the FOLFIRI or FOLFOX-4 chemotherapy regimen		Cycle 2 (Day 1-2), Cycle 3 (Day 1)	No
Secondary	Part 1a - The serum concentration of panitumumab when administered with AMG 706 and either the FOLFIRI or FOLFOX-4 chemotherapy regimen		Cycle 1 (Day 1), Cycle 2 (Day 1), Cycle 4 (Day 1)	No
Secondary	Part 1a - The incidence of HAPA response following panitumumab administration		Cycle 1 (Day 1), Cycle 4 (Day 1), End of Study	Yes
Secondary	Part 1a - The PK of 5-FU when administered as a part of the FOLFIRI or FOLFOX-4 regimen with panitumumab and AMG 706		Cycle 1 and 2 (Day 3)	No

External Links

•   AmgenTrials clinical trials website