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

• Sponsor: University of Rochester (Other)
• Overall Status: Completed
• CT.gov ID: NCT01308840
• Collaborator: Amgen (Industry)
• Enrollment: 31
• Locations: 2
• Arm: 1
• Duration (Months): 25
• Patients Per Site: 15.5
• Patients Per Site Per Month: 0.6

Study Details

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
• 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: Dec 1, 2010
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Jan 1, 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 Names: 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. [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 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 [enrollment until date of death]

   Death from any cause was used.

3. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana-Farber / Harvard Cancer Center	Boston	Massachusetts	United States	02215
2	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Aram Hezel, Professor, University of Rochester
• ClinicalTrials.gov Identifier: NCT01308840
• Other Study ID Numbers: UGIH09067
• First Posted: Mar 4, 2011
• Last Update Posted: Aug 17, 2016
• Last Verified: Jul 1, 2016

• Keywords provided by Aram Hezel, Professor, University of Rochester: Unresectable; metastatic; biliary tract; gallbladder cancer
• Additional relevant MeSH terms: Biliary Tract Neoplasms; Gallbladder Neoplasms; Gemcitabine; Oxaliplatin; Panitumumab

Study Results

Participant Flow

Recruitment Details	38 participants were screened.
Pre-assignment Detail	5 subjects were not eligible to enroll. 2 participants did not receive the intervention.

Arm/Group Title	Panitumumab
Arm/Group Description	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
Period Title: Overall Study
STARTED	31
COMPLETED	31
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Panitumumab
Arm/Group Description	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
Overall Participants	31
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	14 45.2%
Male	17 54.8%
Region of Enrollment (participants) [Number]
United States	31 100%
Eastern Cooperative Oncology Group (ECOG) Performance status (participants) [Number]
0	10 32.3%
1	21 67.7%
Extent of disease (participants) [Number]
locally advanced	2 6.5%
metastatic	29 93.5%
primary tumor site (participants) [Number]
intrahepatic cholangiocarcinoma	25 80.6%
gallbladder	3 9.7%
extrahepatic cholantiocarcinoma	3 9.7%
metastases (participants) [Number]
lymph nodes	24 77.4%
lung	8 25.8%
bone	4 12.9%
omentum/peritoneal	4 12.9%
adrenal	3 9.7%
pelvic soft tissue	1 3.2%

Outcome Measures

1. Primary Outcome

Title	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.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Panitumumab
Arm/Group Description	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
Measure Participants	31
complete response	0 0%
partial response	14 45.2%
stable disease	14 45.2%
progressive disease	3 9.7%

2. Secondary Outcome

Title	Median Progression Free Survival
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Panitumumab
Arm/Group Description	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
Measure Participants	31
Median (Full Range) [months]	10.6

3. Secondary Outcome

Title	Median Overall Survival
Description	Death from any cause was used.
Time Frame	enrollment until date of death

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Panitumumab
Arm/Group Description	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
Measure Participants	31
Median (Full Range) [months]	20.3

4. Secondary Outcome

Title	The Number of Participants Who Experience an Adverse Event
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Panitumumab
Arm/Group Description	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
Measure Participants	31
Number [participants]	31 100%

Adverse Events

Time Frame	Adverse events were collected for the duration of treatment.
Arm/Group Title	Panitumumab
Arm/Group Description	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
All Cause Mortality
	Panitumumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Panitumumab
	Affected / at Risk (%)	# Events
Total	0/31 (0%)
Other (Not Including Serious) Adverse Events
	Panitumumab
	Affected / at Risk (%)	# Events
Total	31/31 (100%)
Blood and lymphatic system disorders
Anaemia	26/31 (83.9%)
neutropenia	7/31 (22.6%)
Leukopenia	19/31 (61.3%)
Thrombocytopenia	24/31 (77.4%)
Hypomagnesemia	21/31 (67.7%)
Gastrointestinal disorders
Nausea	23/31 (74.2%)
abdominal pain	9/31 (29%)
diarrhea	14/31 (45.2%)
General disorders
Fatigue	25/31 (80.6%)
Hepatobiliary disorders
elevated alkaline phosphatase	20/31 (64.5%)
Infections and infestations
infection	4/31 (12.9%)
Nervous system disorders
neuropathy	21/31 (67.7%)
Skin and subcutaneous tissue disorders
rash	20/31 (64.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.