Biliary Tract Cancer, Gallbladder Cancer
Conditions
Keywords
Unresectable, metastatic, biliary tract, gallbladder cancer
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.
Interventions
DRUGPanitumumab
Day 1 and 15 = 6 mg/kg IV
DRUGoxaliplatin
Days 1 and 15 = 85mg/m2 IV
DRUGgemcitabine
Days 1 and 15 = 1000 mg/m2 IV
Sponsors
Amgen
University of Rochester
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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
| Measure | Time frame | Description |
|---|---|---|
| Median Progression Free Survival | 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. |
| Median Overall Survival | enrollment until date of death | Death from any cause was used. |
| The Number of Participants Who Experience an Adverse Event | 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 |
Countries
United States
Participant flow
Recruitment details
38 participants were screened.
Pre-assignment details
5 subjects were not eligible to enroll. 2 participants did not receive the intervention.
Participants by arm
| Arm | Count |
|---|---|
| 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)
Panitumumab: Day 1 and 15 = 6 mg/kg IV
oxaliplatin: Days 1 and 15 = 85mg/m2 IV
gemcitabine: Days 1 and 15 = 1000 mg/m2 IV | 31 |
| Total | 31 |
Baseline characteristics
| Characteristic | Panitumumab |
|---|---|
| Age, Continuous | 61 years |
| Eastern Cooperative Oncology Group (ECOG) Performance status 0 | 10 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance status 1 | 21 participants |
| Extent of disease locally advanced | 2 participants |
| Extent of disease metastatic | 29 participants |
| metastases adrenal | 3 participants |
| metastases bone | 4 participants |
| metastases lung | 8 participants |
| metastases lymph nodes | 24 participants |
| metastases omentum/peritoneal | 4 participants |
| metastases pelvic soft tissue | 1 participants |
| primary tumor site extrahepatic cholantiocarcinoma | 3 participants |
| primary tumor site gallbladder | 3 participants |
| primary tumor site intrahepatic cholangiocarcinoma | 25 participants |
| Region of Enrollment United States | 31 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 31 / 31 |
| serious Total, serious adverse events | 0 / 31 |
Outcome results
Primary
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.
Time frame: end of cycle 2 of treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Panitumumab | 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. | complete response | 0 participants |
| Panitumumab | 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. | partial response | 14 participants |
| Panitumumab | 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. | stable disease | 14 participants |
| Panitumumab | 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. | progressive disease | 3 participants |
Secondary
Median Overall Survival
Death from any cause was used.
Time frame: enrollment until date of death
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab | Median Overall Survival | 20.3 months |
Secondary
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 frame: time to cancer progression or death
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab | Median Progression Free Survival | 10.6 months |
Secondary
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
Time frame: baseline to study completion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panitumumab | The Number of Participants Who Experience an Adverse Event | 31 participants |