Gemcitabine, Oxaliplatin and Panitumumab in Kras/B-raf Wild-Type Biliary Track and Gallbladder Cancer (UGIH09067)

Phase II Study of Gemcitabine, Oxaliplatin in Combination With Panitumumab in Kras/B-raf Wild-Type Unresectable or Metastatic Biliary Track and Gallbladder Cancer

The purpose of this study is to determine disease response of GEMOX-Panitumumab (GEMOX-P) in KRAS/ BRAF wild-type, Stage IV, biliary tract and gallbladder cancer patients who have previously not received chemotherapy. This study will also examine the potential toxicities, progression-free and overall survival in this population.

Study Overview

• Status: Completed
• Conditions: Biliary Tract Cancer; Gallbladder Cancer
• Intervention / Treatment: Drug: Panitumumab; Drug: oxaliplatin; Drug: gemcitabine

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber / Harvard Cancer Center
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed metastatic or unresectable Kras and Braf wild-type biliary tract adenocarcinoma (bile ducts, hepatic duct, cystic duct, common bile duct, ampulla of Vater or gallbladder adenocarcinoma).
• Screening for tumor Kras and Braf mutations requires formalin fixed paraffin embedded tumor blocks from core needle excisional biopsy.
• Participants must have measurable disease.
• No prior chemotherapy for biliary tract or gallbladder cancer. Prior chemoembolization or radiation to the liver allowed as long as measurable disease outside chemoembolization or radiation area and other baseline characteristics met and at least 4 weeks has lapsed since therapy. No prior gemcitabine or oxaliplatin or anti-EGFR therapies including panitumumab therapy allowed.
• Age minimum 18 years old.
• Life expectancy of greater than 3 months.
• ECOG performance status < 1
• Participants must have normal organ and marrow function as defined below:
• Leukocytes > 3,000/mcL Absolute neutrophil count > 1,500/mcL Platelets > 100,000/mcL hemoglobin > 9mg/dL Mg > 1.2 mEq/L total bilirubin < 2.5 mg/dL AST (SGOT)/ALT (SGPT) < 2.5 X institutional upper limit of normal (unless liver is involved with tumor, in which case the transaminases must be 5 x upper limits of normal), creatinine within normal institutional limits or creatinine clearance > 60 mL/min/1.73 m2 for subjects with creatinine levels about institutional normal
• Patients with concurrent malignancy may be included if disease is characterized by one of the following definitions: 1. Malignancy treated with curative intent and with no known active disease present for 3 years prior to randomization and felt to be at low risk for recurrence by the treating physician. 2. Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease. 3. Adequately treated cervical carcinoma in situ without evidence of disease. 4. Prostatic intraepithelial neoplasia without evidence of prostate cancer. 5. DCIS without evidence of breast cancer.
• Ability to understand and the willingness to sign a written informed consent document.
• Patients may have prior placement of stents or shunts to relieve biliary obstruction.

Exclusion Criteria:

• Participants who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Participants may not be receiving any other study agents.
• Participants with known brain metastases.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine, oxaliplatin or panitumumab.
• Patients with preexisting peripheral neuropathy of grade 2 or greater severity according to the Common Terminology Criteria of the NCI (version 3.0) are ineligible.
• Patients with biliary obstruction with inadequate drainage and total bilirubin > 2.5 mg/dL are ineligible.
• 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,
• History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan.
• Known positive test(s) for HIV, hepatitis C virus, acute or chronic active hepatitis B infection.
• Pregnant women are excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Panitumumab; Panitumumab 6mg/kg on days 1 and 15 of every cycle (28 days); Gemcitabine 1000mg/m2 on days 1 and 15 of every cycle (28 days); Oxaliplatin 85mg/m2 on days 1 and 15 of every cycle (28 days)	Drug: Panitumumab; Day 1 and 15 = 6 mg/kg IV; Other Names: GEMOX-Panitumumab (GEMOX-P); Drug: oxaliplatin; Days 1 and 15 = 85mg/m2 IV; Drug: gemcitabine; Days 1 and 15 = 1000 mg/m2 IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Participants With Response to GEMOX-Panitumumab (GEMOX-P) in Chemotherapy naïve KRAS/ BRAF Wild Type Stage IV Biliary Tract Cancer Using the Response Evaluation Criteria In Solid Tumors (RECIST) Criteria.	Tumor measurement - same imaging modality used in pre-treatment evaluation - include radiological examination of all areas with affected disease. For pretreatment and at the end of cycle 2 CT scans (chest/abdomen/pelvis) will be used. For all subsequent cycles, CT of chest/abdomen/pelvis will be used every 8 weeks.	end of cycle 2 of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Progression Free Survival	Progression-free survival was defined as the time from study enrollment to date of cancer progression or death, whichever occurred first. Progression was assessed using CT scans and the Response Evaluation Criteria In Solid Tumors criteria. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	time to cancer progression or death
Median Overall Survival	Death from any cause was used.	enrollment until date of death
The Number of Participants Who Experience an Adverse Event	Any adverse event continuing after the study completion and considered potentially related to study treatment will be followed until resolution, stabilization or initiation of treatment that confounds the ability to assess the event	baseline to study completion

Collaborators and Investigators

• Sponsor: University of Rochester
• Collaborators: Amgen
• Investigators: Principal Investigator: Aram Hezel, MD, University of Rochester

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: August 9, 2010
• First Submitted That Met QC Criteria: March 3, 2011
• First Posted (Estimate): March 4, 2011

Study Record Updates

• Last Update Posted (Estimate): August 17, 2016
• Last Update Submitted That Met QC Criteria: July 7, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Unresectable; metastatic; gallbladder cancer; biliary tract
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Gallbladder Diseases; Biliary Tract Diseases; Biliary Tract Neoplasms; Gallbladder Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Gemcitabine; Oxaliplatin; Panitumumab
• Other Study ID Numbers: UGIH09067