Gemcitabine and Cisplatin Plus Sorafenib in Patients With Advanced Biliary Tract Carcinomas Naive to Systemic Therapy

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00919061
• Collaborator: Bayer (Industry)
• Enrollment: 39
• Location: 1
• Arm: 1
• Duration (Months): 55
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to test an investigational combination of drugs for bile duct or gallbladder cancers.

Gemcitabine and cisplatin are two forms of chemotherapy commonly used in combination to treat bile duct and gallbladder cancers. We are looking to improve treatment results. We will attempt to do so by adding sorafenib (a type of monoclonal antibody) to your treatment plan. Sorafenib acts by attaching to blocking specific targets on cells. These targets may help the cancer cells grow and divide. This study will help answer the question of whether sorafenib is a helpful drug in patients with bile duct or gallbladder cancers when given with gemcitabine and cisplatin.

This study is a phase 2 study. The purpose of a phase 2 study is to find out what effects, good and/or bad, sorafenib in combination with gemcitabine and cisplatin has on advanced bile duct and gallbladder cancers.

Condition or Disease	Intervention/Treatment	Phase
Extrahepatic Bile Duct Cancer; Gallbladder Cancer	Drug: Gemcitabine; Drug: Cisplatin; Drug: Sorafenib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Gemcitabine and Cisplatin Plus Sorafenib in Patients With Advanced Biliary Tract Carcinomas Naïve to Systemic Therapy
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Mar 1, 2014
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gemcitabine and Cisplatin plus Sorafenib This is a non-randomized, open label, single institution, phase II study of gemcitabine and cisplatin plus sorafenib for the treatment of patients with advanced or biliary tract carcinomas naïve to systemic therapy.	Drug: Gemcitabine; Gemcitabine: 800 mg/m^2 over 30 minutes IV, weekly for 2 weeks, followed by a week off treatment.; Drug: Cisplatin; 20 mg /m^2 over 30 minutes IV, weekly for 2 weeks, followed by a week off treatment.; Drug: Sorafenib; 400 mg PO once a day continuously.

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival [6 months]

   Progression free survival will be calculated from study entry to documented disease progression, death from any cause, or drop out due to toxicity, whichever occurs first.

2. Median PFS [6 mos]

   Progression free survival will be calculated from study entry to documented disease progression, death from any cause, or drop out due to toxicity, whichever occurs first.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically / cytologically verified, non-resectable, recurrent, or metastatic biliary tract carcinoma including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma and gallbladder carcinoma. Combined cholangiocarcinoma and hepatocellular carcinoma is allowed.Patients must have uni-dimensionally measurable disease by x-ray, CT scan, MRI scan or physical examination.

• KPS ≥ 80%

• Age ≥ 18 years

• Adequate bone marrow function defined as: Hb ≥ 8 g/dl, ANC ≥ 1.5 K/mcL, Platelets ≥ 100 K/mcL

• Adequate renal function defined as Serum creatinine < 2.0 mg/dl and calculated creatinine clearance ≥ 60 ml/min using the formula:

• Cockcroft-Gault formula:

Cockcroft-Gault Formula - MALES CrCl = (140 - age[years]) (body wt[kg]) (72) (serum creatinine [mg/dL]) Cockcroft-Gault Formula - FEMALES CrCl = 0.85 x male value

• If calculated creatinine clearance is not within range using the above formula, then measured levels from 24-hour urine collection may be used to calculate the creatinine clearance.

• Adequate hepatic function defined as total bilirubin ≤ 2 mg/dl, ALT/AST/ ≤ 3 x ULN (≤ 5 if liver metastases). Patients with biliary obstruction can join if bilirubin corrects to required limit after adequate biliary drainage.

• PT/INR ≤ 1.7 and PTT ≤ 1.5 x ULN, unless the patient is receiving anti-coagulation therapy with agents such as warfarin or heparin

• Patients who have received prior local therapy, i.e. embolization, radiation therapy, etc. (except for chemoembolization) are eligible provided that measurable disease falls outside the treatment field or within the field but has shown an increase of ≥20% in the size. Prior local therapy must be completed at least 4 weeks prior to the baseline scan

• Women of childbearing potential must have a negative pregnancy test.

• Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter. Patients are encouraged to continue barrier method contraception for two years or longer after treatment.

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Any previous chemotherapy, biologic therapy, or investigational agent, except for 5-FU or gemcitabine given as adjuvant therapy as single agents and/or as radio-sensitizing agents. Patient must have completed adjuvant therapy no less than six months prior to accrual. Patients with previous significant allergic hypersensitivity to gemcitabine are excluded.

• Evidence of another active cancer that may influence patient outcome as determined by the Principal Investigator, except for non-melanoma skin carcinoma, melanoma in-situ, in-situ carcinoma of the cervix curatively treated, treated superficial bladder cancer, and adenocarcinoma of the prostate that has been surgically treated with a post-treatment PSA that is non-detectable.

• Known brain metastases

• History of primary central nervous system tumors or brain metastases, and/or seizures not well controlled with standard medical therapy.

• Uncontrolled intercurrent illness including, but not limited to psychiatric illness/social situations that would limit compliance with study requirements.

• Known HIV positive patient

• Blood Pressure of > 150/100 mm Hg

• Significant cardiovascular disease including congestive heart failure (New York Heart Association Class II or higher) or active angina pectoris.

• History of a myocardial infarction within 6 months.

• History of a stroke or transient ischemic attack within 6 months.

• Clinically significant peripheral vascular disease.

• Evidence of bleeding diathesis or coagulopathy.

• Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks.

• Uncontrolled infection.

• Known or suspected allergy to sorafenib or any agent given in the course of this trial.

• Pregnant (positive pregnancy test)

• Breast-feeding should be discontinued if the mother is to be treated on clinical trial.

• Serious non-healing wound, ulcer, or bone fracture

• Use of St. John's Wort or rifampin (rifampicin)

• Any condition that impairs patient's ability to swallow whole pills

• Any malabsorption problem

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• Bayer

Investigators

• Principal Investigator: Ghassan Abou-Alfa, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Memorial Sloan-Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00919061
• Other Study ID Numbers: 09-029
• First Posted: Jun 12, 2009
• Last Update Posted: Feb 3, 2016
• Last Verified: Jan 1, 2016

• Keywords provided by Memorial Sloan Kettering Cancer Center: GALL BLADDER; BILE DUCTS; BAY 43-9006; SORAFENIB; CISPLATIN; GEMCITABINE; 09-029
• Additional relevant MeSH terms: Gallbladder Neoplasms; Bile Duct Neoplasms; Cholangiocarcinoma; Gemcitabine; Sorafenib

Study Results

Participant Flow

Arm/Group Title	Gemcitabine and Cisplatin Plus Sorafenib
Arm/Group Description	This is a non-randomized, open label, single institution, phase II study of gemcitabine and cisplatin plus sorafenib for the treatment of patients with advanced or biliary tract carcinomas naïve to systemic therapy. Gemcitabine and Cisplatin plus Sorafenib: Patients will receive treatment under the following schedule: Gemcitabine: 800 mg/m2 over 30 minutes IV, weekly for 2 weeks, followed by a week off treatment. Cisplatin: 20 mg /m2 over 30 minutes IV, weekly for 2 weeks, followed by a week off treatment. Sorafenib: 400 mg PO once a day continuously. Three weeks of treatment correspond to one cycle.
Period Title: Overall Study
STARTED	39
COMPLETED	37
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Gemcitabine and Cisplatin Plus Sorafenib
Arm/Group Description	This is a non-randomized, open label, single institution, phase II study of gemcitabine and cisplatin plus sorafenib for the treatment of patients with advanced or biliary tract carcinomas naïve to systemic therapy. Gemcitabine and Cisplatin plus Sorafenib: Patients will receive treatment under the following schedule: Gemcitabine: 800 mg/m2 over 30 minutes IV, weekly for 2 weeks, followed by a week off treatment. Cisplatin: 20 mg /m2 over 30 minutes IV, weekly for 2 weeks, followed by a week off treatment. Sorafenib: 400 mg PO once a day continuously. Three weeks of treatment correspond to one cycle.
Overall Participants	39
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	21 53.8%
>=65 years	18 46.2%
Sex: Female, Male (Count of Participants)
Female	19 48.7%
Male	20 51.3%
Region of Enrollment (participants) [Number]
United States	39 100%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival
Description	Progression free survival will be calculated from study entry to documented disease progression, death from any cause, or drop out due to toxicity, whichever occurs first.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine and Cisplatin Plus Sorafenib
Arm/Group Description	This is a non-randomized, open label, single institution, phase II study of gemcitabine and cisplatin plus sorafenib for the treatment of patients with advanced or biliary tract carcinomas naïve to systemic therapy. Gemcitabine and Cisplatin plus Sorafenib: Patients will receive treatment under the following schedule: Gemcitabine: 800 mg/m2 over 30 minutes IV, weekly for 2 weeks, followed by a week off treatment. Cisplatin: 20 mg /m2 over 30 minutes IV, weekly for 2 weeks, followed by a week off treatment. Sorafenib: 400 mg PO once a day continuously. Three weeks of treatment correspond to one cycle.
Measure Participants	37
Number (95% Confidence Interval) [percentage of participants]	51 130.8%

2. Primary Outcome

Title	Median PFS
Description	Progression free survival will be calculated from study entry to documented disease progression, death from any cause, or drop out due to toxicity, whichever occurs first.
Time Frame	6 mos

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine and Cisplatin Plus Sorafenib
Arm/Group Description	This is a non-randomized, open label, single institution, phase II study of gemcitabine and cisplatin plus sorafenib for the treatment of patients with advanced or biliary tract carcinomas naïve to systemic therapy. Gemcitabine and Cisplatin plus Sorafenib: Patients will receive treatment under the following schedule: Gemcitabine: 800 mg/m2 over 30 minutes IV, weekly for 2 weeks, followed by a week off treatment. Cisplatin: 20 mg /m2 over 30 minutes IV, weekly for 2 weeks, followed by a week off treatment. Sorafenib: 400 mg PO once a day continuously. Three weeks of treatment correspond to one cycle.
Measure Participants	37
Progression Free Survival	6.5
Overall Survival	14.4

Adverse Events

Arm/Group Title	Gemcitabine and Cisplatin Plus Sorafenib
Arm/Group Description	This is a non-randomized, open label, single institution, phase II study of gemcitabine and cisplatin plus sorafenib for the treatment of patients with advanced or biliary tract carcinomas naïve to systemic therapy. Gemcitabine and Cisplatin plus Sorafenib: Patients will receive treatment under the following schedule: Gemcitabine: 800 mg/m2 over 30 minutes IV, weekly for 2 weeks, followed by a week off treatment. Cisplatin: 20 mg /m2 over 30 minutes IV, weekly for 2 weeks, followed by a week off treatment. Sorafenib: 400 mg PO once a day continuously. Three weeks of treatment correspond to one cycle.
All Cause Mortality
	Gemcitabine and Cisplatin Plus Sorafenib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gemcitabine and Cisplatin Plus Sorafenib
	Affected / at Risk (%)	# Events
Total	24/39 (61.5%)
Blood and lymphatic system disorders
Febrile neutropenia	2/39 (5.1%)	2
Anemia	2/39 (5.1%)	2
Hemorrhage/Bleeding, other	1/39 (2.6%)	1
Eye disorders
Vision-blurred vision	1/39 (2.6%)	1
Gastrointestinal disorders
Ascites	2/39 (5.1%)	2
Colitis, infectious	1/39 (2.6%)	1
Constipation	2/39 (5.1%)	2
Diarrhea	2/39 (5.1%)	2
Dry mouth/salivary gland (xerostomia)	1/39 (2.6%)	1
Gastrointestinal, other	2/39 (5.1%)	3
Fecal incontinence	1/39 (2.6%)	1
Nausea	3/39 (7.7%)	3
Abdominal pain	7/39 (17.9%)	9
Vomiting	5/39 (12.8%)	5
General disorders
Death-Disease Progression	3/39 (7.7%)	3
Fatigue (asthenia, lethargy, malaise)	1/39 (2.6%)	1
Fever	5/39 (12.8%)	6
Chest pain	1/39 (2.6%)	1
Pain-Other	3/39 (7.7%)	3
Chills	1/39 (2.6%)	1
Hepatobiliary disorders
Gallbladder obstruction	1/39 (2.6%)	1
Infections and infestations
Infection	4/39 (10.3%)	4
Investigations
Bilirubin (hyperbilirubinemia)	1/39 (2.6%)	2
Blood disorder	1/39 (2.6%)	1
Cardiac troponin I increased	1/39 (2.6%)	1
Neutrophil count decreased	2/39 (5.1%)	2
Platelet count decrease	3/39 (7.7%)	3
Metabolism and nutrition disorders
Dehydration	1/39 (2.6%)	1
Hyperglycemia	1/39 (2.6%)	1
Hyponatremia	1/39 (2.6%)	1
Musculoskeletal and connective tissue disorders
Back pain	2/39 (5.1%)	2
Neck Pain	1/39 (2.6%)	1
Nervous system disorders
Headache	2/39 (5.1%)	2
Renal and urinary disorders
Ureteric obstruction	1/39 (2.6%)	1
Renal failure	1/39 (2.6%)	1
Urogenital disorder	1/39 (2.6%)	1
Urinary frequency/urgency	1/39 (2.6%)	1
Reproductive system and breast disorders
Fistula, GU - Vagina	1/39 (2.6%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	1/39 (2.6%)	1
Hiccoughs (hiccups, singultus)	1/39 (2.6%)	1
Skin and subcutaneous tissue disorders
Skin infection	2/39 (5.1%)	2
Rash: erythema multiforme	1/39 (2.6%)	1
Vascular disorders
Hypertension	2/39 (5.1%)	2
Hypotension	1/39 (2.6%)	1
Thrombosis	8/39 (20.5%)	9
Other (Not Including Serious) Adverse Events
	Gemcitabine and Cisplatin Plus Sorafenib
	Affected / at Risk (%)	# Events
Total	37/39 (94.9%)
Blood and lymphatic system disorders
Anemia	30/39 (76.9%)	366
Ear and labyrinth disorders
Tinnitus	3/39 (7.7%)	3
Gastrointestinal disorders
Constipation	5/39 (12.8%)	5
Diarrhea	6/39 (15.4%)	10
Nausea	2/39 (5.1%)	2
General disorders
Fatigue	17/39 (43.6%)	25
Chest pain	2/39 (5.1%)	2
Pain-other	2/39 (5.1%)	2
Infections and infestations
Infection, other	3/39 (7.7%)	3
Investigations
Alanine aminotransferase increased	11/39 (28.2%)	30
Aspartate aminotransferase increased	8/39 (20.5%)	12
Serum amylase increased	8/39 (20.5%)	26
Blood bilirubin increased	6/39 (15.4%)	19
Creatinine increased	2/39 (5.1%)	13
White blood cell decreased	16/39 (41%)	66
Lipase increased	13/39 (33.3%)	24
Lymphocyte count decreased	9/39 (23.1%)	15
Neutrophil count decreased	15/39 (38.5%)	64
Platelet count decreased	16/39 (41%)	35
Metabolism and nutrition disorders
Hypoalbuminemia	17/39 (43.6%)	59
Alkaline phosphatase increased	16/39 (41%)	69
Anorexia	3/39 (7.7%)	3
Hyperglycemia	17/39 (43.6%)	68
Hypomagnesemia	3/39 (7.7%)	3
Hypophosphatemia	8/39 (20.5%)	20
Hyperkalemia	4/39 (10.3%)	8
Hyponatremia	4/39 (10.3%)	11
Musculoskeletal and connective tissue disorders
Back Pain	3/39 (7.7%)	3
Nervous system disorders
Peripheral sensory neuropathy	3/39 (7.7%)	5
Skin and subcutaneous tissue disorders
Rash	2/39 (5.1%)	2
Rash-Hand Foot Skin Reaction	10/39 (25.6%)	13
Vascular disorders
Hypertension	2/39 (5.1%)	2
Thrombosis	5/39 (12.8%)	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.