Phase II Study of Irinotecan and Panitumumab

NCT00836277 | Completed Phase 2 Results DMC

• 1 other identifier: 07-161
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Esophageal Cancer

Keywords

Panitumumab; Irinotecan; Esophageal Adenocarcinoma; Phase II

Outcome Measures

Primary Outcomes (2)

• Response Rate (RR)

  Response rate (RR) = the # participants with partial response (PR) + # participants with (CR) / # participants with (PR) + # participants with (CR ) + # participants with (SD) + # participants with (PD). This proportion was subsequently multiplied by 100. RECIST v1.0 criteria for Target Lesions was used: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started

  Up to 14 months

• Clinical Benefit Rate (CBR)

  Using RECIST v1.0 criteria, clinical benefit rate (CBR) = # participants with (PR) + # participants with (CR) + # participants with (SD) / # participants with (PR) + # participants with (CR) + # participants with (SD) + # participants with (PD). This proportion was subsequently multiplied by 100. RECIST v1.0 criteria for Target Lesions is defined as: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

  Up to 14 months

Secondary Outcomes (3)

• Progression-free Survival (PFS)

  Up to 45 months (cohort)

• Overall Survival (OS)

  Up to 45 months (cohort)

• 1-year (Overall) Survival Rate

  1 year

Study Arms (1)

Irinotecan plus panitumumab

EXPERIMENTAL

Irinotecan 100 mg/m2 IV Day 1 and Day 8 \+ Panitumumab 9mg/kg IV Day 1 Cycle = 21 days

Drug: Panitumumab; Drug: Irinotecan

Interventions

Panitumumab DRUG

9mg/kg IV Day 1 Cycle = 21 days

Also known as: ABX-EGF

Irinotecan plus panitumumab

Irinotecan DRUG

125mg/m2 IV Day 1 and Day 8

Also known as: Camptosar, Campto, CPT-11

Irinotecan plus panitumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed diagnosis of locally recurrent or metastatic adenocarcinoma of the esophagus which is incurable with standard therapy.
• Patients must have measurable disease outside a previous radiation port, or which has developed in the port since the conclusion of radiation and is biopsy-proven to be recurrent cancer.
• One prior chemotherapy regimen for metastatic disease, with the exception of prior irinotecan or panitumumab.
• Prior radiation therapy to no more than 20% of the bone marrow is allowed. No treatment with wide field radiation within 4 weeks of entry onto this study.
• Full recovery from the effects of any prior surgery.
• Man or woman \>18 years of age.
• ECOG performance status \<2 (Karnofsky \>60%)
• Life expectancy of \>3 months
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Hemoglobin ≥ 9.0 g/dL
• Creatinine \< or = to 1.5 mg/dL
• Creatinine clearance \> or = to 50 mL/min calculated by the Cockcroft-Gault method as follows:
• Male creatinine clearance = (140 - age) x (weight in Kg) / (serum Cr x 72)
• Female creatinine clearance = (140 - age) x (weight in Kg) x 0.85 / (serum Cr x 72)

You may not qualify if:

• History or known presence of central nervous system (CNS) metastases unless CNS metastases have been irradiated and are stable.
• History of another primary cancer, except:
• Curatively treated in situ cervical cancer
• Curatively resected non-melanoma skin cancer
• Other primary solid tumor curatively treated with no known active disease present and no treatment administered for greater than or equal to 5 years prior to enrollment
• Pre-existing peripheral neuropathy \> grade 1.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to panitumumab or irinotecan.
• Patients receiving any medications or substances that are established or probable inhibitors or inducers of P450 3A4 are ineligible.
• Prior anti-EGFr antibody therapy (eg, cetuximab) or treatment with small molecule EGFr inhibitors (eg, gefitinib, erlotinib, lapatinib)
• Radiotherapy \< or = to 14 days prior to enrollment.
• Systemic chemotherapy, hormonal therapy, immunotherapy, or experimental or approved proteins/antibodies (or small molecules for Phase I studies) (eg, bevacizumab)\< or = to 30 days before enrollment
• Subjects requiring chronic use of immunosuppressive agents (eg, methotrexate, cyclosporine)
• Any investigational agent or therapy \< or = to 30 days before enrollment
• Prior therapy with Irinotecan or panitumumab.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• Weijing Sun, MD, FACP: lead
• Amgen: collaborator

Study Sites (1)

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (1)

• Yoon H, Karapetyan L, Choudhary A, Kosozi R, Bali GS, Zaidi AH, Atasoy A, Forastiere AA, Gibson MK. Phase II Study of Irinotecan Plus Panitumumab as Second-Line Therapy for Patients with Advanced Esophageal Adenocarcinoma. Oncologist. 2018 Sep;23(9):1004-e102. doi: 10.1634/theoncologist.2017-0657. Epub 2018 May 16.

  PMID: 29769385 DERIVED

MeSH Terms

Conditions

Esophageal Neoplasms; Adenocarcinoma Of Esophagus

Interventions

Panitumumab; Irinotecan

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Weijing Sun, MD
• Organization: University of Pittsburgh Cancer Institute

sunw@upmc.edu

412-864-7764

Study Officials

• Weijing Sun, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: February 3, 2009
• First Posted: February 4, 2009
• Study Start: May 1, 2009
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: November 15, 2016
• Results First Posted: November 15, 2016

Record last verified: 2016-09

Locations

US (1)