Trastuzumab in Treating Patients With Locally Advanced or Metastatic Gallbladder Cancer or Bile Duct Cancer That Cannot Be Removed by Surgery

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT00478140
• Collaborator: (none)
• Enrollment: 4
• Locations: 2
• Arm: 1
• Duration (Months): 54
• Patients Per Site: 2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial is studying how well trastuzumab works in treating patients with locally advanced or metastatic gallbladder cancer or bile duct cancer that cannot be removed by surgery. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Extrahepatic Bile Duct; Adenocarcinoma of the Gallbladder; Malignant Neoplasm; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer	Biological: trastuzumab; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

1. Determine the objective response rate and duration of objective response in patients with HER2/neu-positive advanced gallbladder or biliary tract cancer treated with trastuzumab (Herceptin).

SECONDARY OBJECTIVES:

1. Assess the safety and tolerability of this drug in these patients. II. Assess the progression-free survival and overall survival of patients treated with this drug.

OUTLINE:

Patients receive trastuzumab intravenously over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study Trastuzumab (NSC 688097) in Her2/Neu Positive Cancer of the Gallbladder or Biliary Tract (NCI 7756)
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Nov 1, 2011
• Actual Study Completion Date: Nov 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Trastuzumab Participants receive trastuzumab loading dose 8 mg/kg intravenous (IV) over 30-90 minutes on day 1 and subsequent maintenance doses of 6 mg/kg over 90 minutes then every 30 minutes starting at the third dose. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Biological: trastuzumab; For HER-2/neu positive biopsies, trastuzumab was administered intravenously, once every 3 weeks, at a loading first dose at 8 mg/kg over 90 minutes, and subsequent maintenance doses of 6 mg/kg over 90 minutes then every 30 minutes starting at the third dose.; Other Names: anti-c-erB-2 Herceptin MOAB HER2 ; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Objective Response (Complete and Partial Response) [Baseline to 63 days or until disease progression]

   Response assessed using imaging-based evaluation at baseline then following single agent trastuzumab administered over 21 day cycle, re-staging done following 2 cycles. Response Evaluation Criteria in Solid Tumors defined as Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in sum of longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Secondary Outcome Measures

1. Disease Control Rate [Up to 3.5 years]

   Percentage of participants who have achieved complete response, partial response and stable disease

2. Number of Participant With Toxicity Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 [Up to 3 years]

   Participant toxicity for study as assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 reported in Results Adverse Event Reporting of record.

3. Overall Survival [Up to 3.5 years]

   Length of time from date of starting treatment that participants are still alive

Eligibility Criteria

Criteria

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

Criteria:

• Adenocarcinoma of the gallbladder

• Recurrent extrahepatic bile duct cancer

• Recurrent gallbladder cancer

• Unresectable extrahepatic bile duct cancer

• Adenocarcinoma of the extrahepatic bile duct

• Unresectable gallbladder cancer

• Prior surgery and radiotherapy allowed

• At least 28 days since prior chemotherapy (6 weeks for nitrosoureas and mitomycin C) and recovered

• No other concurrent investigational agents, chemotherapy, radiotherapy, or hormonal therapy

• Concurrent hormones administered for nondisease-related conditions (e.g., insulin for diabetes) allowed

• No concurrent corticosteroids or anticonvulsants

• Concurrent steroids administered for antiemesis, adrenal failure, or septic shock allowed

• No concurrent combination antiretroviral therapy for HIV-positive patients

• Histologically or cytologically confirmed adenocarcinoma of the gallbladder or bile duct, meeting all of the following criteria: locally advanced or metastatic disease that is unresectable

• Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques or >= 10 mm by spiral computed tomography (CT) scan

• Tumor that recurs within a previously irradiated field is considered measurable disease if recurrence is documented and measurable by Response Evaluation Criteria in Solid Tumors (RECIST) criteria

• Tumor must be Her2/neu positive by Fluorescence in situ hybridization (FISH)testing

• No symptomatic brain metastases

• The Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 OR Karnofsky PS 60-100%

• Absolute neutrophil count (ANC) >= 1,500/mm^3

• Fertile patients must use effective contraception prior to, during, and for >= 3 months after completion of study treatment

• Creatinine =< 2 times upper limits of normal (ULN) OR creatinine clearance >= 60 mL/min

• No other active malignancy

• Left Ventricular Ejection Fraction (LVEF) >= 50%

• No concurrent uncontrolled illness

• No ongoing or active infection requiring systemic IV antibiotics on day 1 of treatment

• No symptomatic New York Heart Association class III-IV congestive heart failure

• No unstable angina pectoris

• No unstable cardiac arrhythmia requiring medication

• No more than 1 prior systemic chemotherapy regimen

• White Blood Count (WBC) >= 3,000/mm^3

• Platelet count >= 40,000/mm^3

• Bilirubin =< 4 mg/dL

• Aspartate aminotransferase and alanine aminotransferase (AST and ALT) =< 5 times upper limit of normal (ULN)

• Not pregnant or nursing

• Negative pregnancy test

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Southern California, Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
2	The University of Texas (UT) MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ahmed Kaseb, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• The University of Texas MD Anderson Cancer Center official website

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00478140
• Other Study ID Numbers: NCI-2009-00217; 2006-0851; N01CM62202
• First Posted: May 24, 2007
• Last Update Posted: Aug 20, 2019
• Last Verified: Jul 1, 2019

• Additional relevant MeSH terms: Adenocarcinoma; Neoplasms; Gallbladder Neoplasms; Bile Duct Neoplasms; Cholangiocarcinoma; Recurrence; Trastuzumab

Study Results

Participant Flow

Recruitment Details	Recruitment Period: May 30, 2007 to June 15, 2009. All recruitment done in medical clinics.
Pre-assignment Detail	Of the 53 participants pre-screened only four participants were enrolled in the study.

Arm/Group Title	Trastuzumab
Arm/Group Description	Trastuzumab loading dose 8 mg/kg intravenous (IV) over 30-90 minutes on day 1 and subsequent maintenance doses of 6 mg/kg over 90 minutes then every 30 minutes starting at the third dose. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	4
COMPLETED	3
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Trastuzumab
Arm/Group Description	Trastuzumab loading dose 8 mg/kg intravenous (IV) over 30-90 minutes on day 1 and subsequent maintenance doses of 6 mg/kg over 90 minutes then every 30 minutes starting at the third dose. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Participants	4
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	52
Sex: Female, Male (Count of Participants)
Female	2 50%
Male	2 50%
Region of Enrollment (participants) [Number]
United States	4 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response (Complete and Partial Response)
Description	Response assessed using imaging-based evaluation at baseline then following single agent trastuzumab administered over 21 day cycle, re-staging done following 2 cycles. Response Evaluation Criteria in Solid Tumors defined as Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in sum of longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time Frame	Baseline to 63 days or until disease progression

Outcome Measure Data

Analysis Population Description

Only those participants who had measurable disease present at baseline, received at least one cycle of therapy, and had disease re-evaluated considered evaluable for response; therefore one participant was inevaluable.

Arm/Group Title	Trastuzumab
Arm/Group Description	Trastuzumab loading dose 8 mg/kg intravenous (IV) over 30-90 minutes on day 1 and subsequent maintenance doses of 6 mg/kg over 90 minutes then every 30 minutes starting at the third dose. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	3
Complete Response	1 25%
Partial Response	0 0%
Progressive Disease	1 25%
Stable Disease	1 25%

2. Secondary Outcome

Title	Disease Control Rate
Description	Percentage of participants who have achieved complete response, partial response and stable disease
Time Frame	Up to 3.5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Trastuzumab
Arm/Group Description	Trastuzumab loading dose 8 mg/kg intravenous (IV) over 30-90 minutes on day 1 and subsequent maintenance doses of 6 mg/kg over 90 minutes then every 30 minutes starting at the third dose. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	3
Number [percentage of participants]	67 1675%

3. Secondary Outcome

Title	Number of Participant With Toxicity Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Description	Participant toxicity for study as assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 reported in Results Adverse Event Reporting of record.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Trastuzumab
Arm/Group Description	Trastuzumab loading dose 8 mg/kg intravenous (IV) over 30-90 minutes on day 1 and subsequent maintenance doses of 6 mg/kg over 90 minutes then every 30 minutes starting at the third dose. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	3
Number [participants]	3 75%

4. Secondary Outcome

Title	Overall Survival
Description	Length of time from date of starting treatment that participants are still alive
Time Frame	Up to 3.5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Trastuzumab
Arm/Group Description	Trastuzumab loading dose 8 mg/kg intravenous (IV) over 30-90 minutes on day 1 and subsequent maintenance doses of 6 mg/kg over 90 minutes then every 30 minutes starting at the third dose. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	3
Median (Full Range) [weeks]	65

Adverse Events

Time Frame	2 years and 9 months
Arm/Group Title	Trastuzumab
Arm/Group Description	Trastuzumab loading dose 8 mg/kg intravenous (IV) over 30-90 minutes on day 1 and subsequent maintenance doses of 6 mg/kg over 90 minutes then every 30 minutes starting at the third dose. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Trastuzumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Trastuzumab
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Other (Not Including Serious) Adverse Events
	Trastuzumab
	Affected / at Risk (%)	# Events
Total	4/4 (100%)
Blood and lymphatic system disorders
Alkaline phosphatase increased	2/4 (50%)
Blood bilirubin increased	3/4 (75%)
Creatinine increased	1/4 (25%)
Hyperkalemia	1/4 (25%)
Hyponatremia	1/4 (25%)
Alanine aminotransferase increased	1/4 (25%)
Aspartate aminotransferase increased	2/4 (50%)
Hematuria	1/4 (25%)
Anemia	1/4 (25%)
Cardiac disorders
Myalgia	2/4 (50%)
Ear and labyrinth disorders
Tinnitus	1/4 (25%)
Gastrointestinal disorders
Abdominal distension	2/4 (50%)
Abdominal pain	3/4 (75%)
Anorexia	3/4 (75%)
Ascites	3/4 (75%)
Diarrhea	2/4 (50%)
Gastrointestinal disorders	2/4 (50%)
Nausea	4/4 (100%)
Vomiting	3/4 (75%)
Constipation	3/4 (75%)
Dysgeusia	1/4 (25%)
General disorders
Fatigue	4/4 (100%)
Insomnia	3/4 (75%)
Headache	3/4 (75%)
Immune system disorders
Allergic reaction	2/4 (50%)
Allergic rhinitis	2/4 (50%)
Infections and infestations
Fever	1/4 (25%)
Upper respiratory infection	1/4 (25%)
Investigations
Weight loss	2/4 (50%)
Chills	2/4 (50%)
Metabolism and nutrition disorders
Dehydration	2/4 (50%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/4 (50%)
Back pain	2/4 (50%)
Joint range of motion decreased lumbar spine	1/4 (25%)
Neck pain	1/4 (25%)
Nervous system disorders
Dizziness	1/4 (25%)
Hyperhidrosis	1/4 (25%)
Peripheral sensory neuropathy	1/4 (25%)
Psychiatric disorders
Anxiety	1/4 (25%)
Renal and urinary disorders
Cystitis noninfective	1/4 (25%)
Respiratory, thoracic and mediastinal disorders
Mucositis oral	1/4 (25%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/4 (25%)
Pruritus	1/4 (25%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.