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

• ClinicalTrials.gov Identifier: NCT01308840
• Recruitment Status: Completed
• First Posted: March 4, 2011
• Results First Posted: August 17, 2016
• Last Update Posted: August 17, 2016
• Sponsor: University of Rochester
• Collaborator: Amgen
• Information provided by (Responsible Party): Aram Hezel, University of Rochester

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Biliary Tract Cancer; Gallbladder Cancer	Drug: Panitumumab; Drug: oxaliplatin; Drug: gemcitabine	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 31 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Gemcitabine, Oxaliplatin in Combination With Panitumumab in Kras/B-raf Wild-Type Unresectable or Metastatic Biliary Track and Gallbladder Cancer
• Study Start Date: December 2010
• Actual Primary Completion Date: January 2013
• Actual Study Completion Date: January 2013

Arms and Interventions

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 Name: GEMOX-Panitumumab (GEMOX-P); Drug: oxaliplatin; Days 1 and 15 = 85mg/m2 IV; Drug: gemcitabine; Days 1 and 15 = 1000 mg/m2 IV

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: end of cycle 2 of treatment ]
   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.

Secondary Outcome Measures :

1. Median Progression Free Survival [ Time Frame: time to cancer progression or death ]
   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.
2. Median Overall Survival [ Time Frame: enrollment until date of death ]
   Death from any cause was used.
3. The Number of Participants Who Experience an Adverse Event [ Time Frame: baseline to study completion ]
   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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Massachusetts

Dana-Farber / Harvard Cancer Center

Boston, Massachusetts, United States, 02215

United States, New York

University of Rochester Medical Center

Rochester, New York, United States, 14642

Sponsors and Collaborators

University of Rochester

Amgen

Investigators

• Principal Investigator: Aram Hezel, MD; University of Rochester

More Information

• Responsible Party: Aram Hezel, Professor, University of Rochester
• ClinicalTrials.gov Identifier: NCT01308840
• Other Study ID Numbers: UGIH09067
• First Posted: March 4, 2011
• Results First Posted: August 17, 2016
• Last Update Posted: August 17, 2016
• Last Verified: July 2016

Keywords provided by Aram Hezel, University of Rochester:

Unresectable; metastatic; biliary tract; gallbladder cancer

Additional relevant MeSH terms:

Biliary Tract Neoplasms; Gallbladder Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Gallbladder Diseases; Gemcitabine; Oxaliplatin; Panitumumab; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents, Immunological