Phase II Study of Irinotecan and Panitumumab
This study proposes a single-arm, phase II study of irinotecan with panitumumab as second-line therapy for patients with advanced esophageal adenocarcinoma. Efficacy will be assessed by response rate, with an exploratory outcome endpoint of time to progression (as panitumumab may result in prolonged stable disease). In addition to the usual safety assessments, molecular correlates will be carried out in order to search for pharmacodynamic and pharmacogenomic features that may correlate with response. Measures of host/patient immune function will be assessed by evaluating the relationship between Fc receptor polymorphisms and response in patients treated with panitumumab. Measures of EGFR protein and phosphoprotein expression by immunohistochemical- (IHC-) staining, K-ras mutation status1 and reverse-phase protein arrays (RPPA) and EGFR gene amplification by fluorescence in situ hybridization (FISH) will be assessed as exploratory correlates.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Irinotecan and Panitumumab as Second-Line Therapy for Patients With Advanced Esophageal Adenocarcinoma|
- Overall Best Response Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Safety and Toxicity - All patients who receive any amount of study drug will be evaluable for toxicity. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Time to Progression [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- 6 and 12-month Overall Survival [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Overall Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Duration of Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Exploratory Correlative Studies [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||May 2009|
|Estimated Study Completion Date:||June 2014|
|Estimated Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
Experimental: Irinotecan plus panitumumab
Irinotecan 100 mg/m2 IV Day 1 and Day 8
+ Panitumumab 9mg/kg IV Day 1 Cycle = 21 days
9mg/kg IV Day 1 Cycle = 21 days
Other Name: ABX-EGFDrug: Irinotecan
125mg/m2 IV Day 1 and Day 8
Esophageal cancer is a highly lethal malignancy that is increasing in incidence, especially the histologic subtype of adenocarcinoma. Fully 50% of patients present with advanced, incurable disease. Of the remainder who are diagnosed at curable stages, at most 30% are long-term survivors. Advances in therapy for both local and advanced disease have been stagnant in the past few decades. As such, there is an urgent need for advances in therapy. The development of modern cytotoxic chemotherapy and in particular, biologically targeted agents, provides hope for improving the outcome in these patients.
The semi-synthetic derivative of camptothecin, irinotecan, is active in esophageal adenocarcinoma, both alone and in combination with cisplatin. Use as front-line therapy in both multi-modality regimens and combination chemotherapy is common. More recently, the elucidation of the role of the epidermal growth factor receptor (EGFR) pathway in esophageal cancer has resulted in the pre-clinical and clinical study of the activity of EGFR directed agents for treatment of esophageal cancer.
The anti-EGFR antibodies, panitumumab and cetuximab, are active as both single agents and in combination with cytotoxic chemotherapy in patients with colorectal adenocarcinoma. In particular, the combination of irinotecan and cetuximab is active for irinotecan refractory colorectal cancer, while panitumumab is active compared with best supportive care. In our clinic, we have empiric evidence for the unexpectedly significant activity of the combination of cetuximab and irinotecan as third-line treatment for advanced esophageal adenocarcinoma. Panitumumab has the clinical advantages, compared with cetuximab, of being fully human,, thus resulting in a lower frequency of infusion reactions.
This recent experience with these targeted agents in solid tumors, while still promising, has yielded relatively modest results.7-11 Notably, however, retrospective analyses of clinical trials are consistently revealing that differences in treatment effect between subgroups of patients can be associated with specific molecular profiles.12-18 These findings suggest the potential for a more rational approach to trial design that would use patient and tumor characteristics to select patients for therapy, thus enriching the population of responders.
|Contact: Michael K Gibson, MDfirstname.lastname@example.org|
|United States, Pennsylvania|
|University of Pittsburgh Cancer Institute||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15232|
|Contact: Michael K Gibson, MD 412-692-2600 email@example.com|
|Principal Investigator:||Michael Gibson, MD||University of Pittsburgh|