Trial Outcomes & Findings for Bortezomib in Treating Patients With Unresectable Locally Advanced or Metastatic Adenocarcinoma of the Bile Duct or Gallbladder (NCT NCT00085410)

Last Updated: 2017-07-02

Results Overview

Objective Response Rate (ORR) was determined by best response on radiologic assessment (computed tomography or magnetic resonance imaging) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

20 participants

Primary outcome timeframe

Up to 1 year

Results posted on

2017-07-02

Participant Flow

Participants were recruited through physician referral at: Fox Chase Cancer Center. The trial was discontinued early due to no confirmed partial responses.

Twenty individuals were enrolled in this study over a four year period.

Participant milestones

Participant milestones
Measure	Arm I Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11.
Overall Study STARTED	20
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Bortezomib in Treating Patients With Unresectable Locally Advanced or Metastatic Adenocarcinoma of the Bile Duct or Gallbladder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I n=20 Participants Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11.
Site of Metastases Lymph nodes	7 participants n=5 Participants
Site of Metastases Lung	5 participants n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=5 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants
Site of Primary Tumor Gallbladder	6 participants n=5 Participants
Site of Primary Tumor Intrahepatic or extrahepatic cholangiocarcinoma	14 participants n=5 Participants
Site of Metastases Liver	14 participants n=5 Participants
Site of Metastases Other	2 participants n=5 Participants
Eastern Cooperative Oncology Group Performance Status Grade 0	7 participants n=5 Participants
Eastern Cooperative Oncology Group Performance Status Grade 1	13 participants n=5 Participants
Previous Treatment None	10 participants n=5 Participants
Previous Treatment Chemotherapy only	4 participants n=5 Participants
Previous Treatment Chemotherapy/radiation therapy	5 participants n=5 Participants
Previous Treatment Other	1 participants n=5 Participants
Previous Surgery Yes: Cholecystectomy	4 participants n=5 Participants
Previous Surgery Yes: Liver section	1 participants n=5 Participants
Previous Surgery No	15 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 1 year

Population: Per protocol

Outcome measures

Outcome measures
Measure	Arm I n=20 Participants Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11.
Objective Response Rate Stable Disease	10 Participants
Objective Response Rate Partial Response (Unconfirmed)	1 Participants
Objective Response Rate Progressive Disease	8 Participants
Objective Response Rate Withdrew Consent Before Evaluation	1 Participants

SECONDARY outcome

Timeframe: Up to 1 year

Population: 1 patient who withdrew consent prior to the first disease evaluation was excluded.

Time from initiation of therapy to first progressive disease.

Outcome measures

Outcome measures
Measure	Arm I n=19 Participants Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11.
Time to Disease Progression	5.8 months Interval 0.7 to 77.6

SECONDARY outcome

Timeframe: Up to 1 year

Population: 1 patient who withdrew consent prior to the first disease evaluation was excluded.

The time from initiation of therapy to death or last follow-up.

Outcome measures

Outcome measures
Measure	Arm I n=19 Participants Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11.
Overall Survival	9 months Interval 4.6 to 18.5

SECONDARY outcome

Timeframe: Once in the screening period (within 14 days of starting treatment)

Population: Insufficient amount of patient samples collected for analysis

Proteasome inhibition compared between tumor specimens and peripheral blood. Sufficient tissue samples are required for this analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Once in the screening period (within 14 days of starting treatment)

Population: Insufficient amount of patient samples collected for analysis

Evaluation of clinical outcomes with expression of molecular markers specified and others. Sufficient amount of biliary washings and tumor biopsies needed for analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Duration of study treatment

Population: Insufficient amount of patient samples collected for analysis

Phenotypic expression of molecular markers before and after study treatment

Outcome measures

Outcome data not reported

POST_HOC outcome

Timeframe: Up to 1 year

Population: 1 patient who withdrew consent prior to the first disease evaluation was excluded.

Best response to study treatment was confirmed complete response, partial response, or stable disease. Unconfirmed partial response was not included. The outcome measure data table is stratified into patients who a) received prior therapy b) did not receive prior therapy.

Outcome measures

Outcome measures
Measure	Arm I n=19 Participants Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11.
Clinical Benefit Rate Patients who received prior therapy	21 percentage of patients
Clinical Benefit Rate Patients who did not receive prior therapy	32 percentage of patients

POST_HOC outcome

Timeframe: 6 months

Population: 1 patient who withdrew consent prior to the first disease evaluation was excluded.

The time from initiation of therapy to 6 months beyond.

Outcome measures

Outcome measures
Measure	Arm I n=19 Participants Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11.
6-Month Survival	70 percentage of patients

POST_HOC outcome

Timeframe: 1 year

Population: 1 patient who withdrew consent prior to the first disease evaluation was excluded.

The time from initiation of initiation of therapy to 1 year beyond.

Outcome measures

Outcome measures
Measure	Arm I n=19 Participants Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11.
1-year Survival	38 percentage of patients

POST_HOC outcome

Timeframe: Up to 1 year

Population: Patients who derived benefit from study treatment (stable disease, partial response, or complete response was best response)

The time from initiation of therapy to 6 months beyond. Only patients who derived benefit from study treatment (stable disease, partial response, or complete response was best response) were included.

Outcome measures

Outcome measures
Measure	Arm I n=10 Participants Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11.
6-Month and 1-Year Survival for Patients Who Derived Clinical Benefit From Study Treatment 6-Month Survival	90 percentage of patients
6-Month and 1-Year Survival for Patients Who Derived Clinical Benefit From Study Treatment 1-Year Survival	69 percentage of patients

POST_HOC outcome

Timeframe: Up to 1 year

Population: Patients who did not derive clinical benefit from study treatment (progressive disease was best response) only.

The time from initiation of therapy to 6 months beyond. Only patients who did not derive clinical benefit from study treatment (progressive disease or unconfirmed partial response was best response) were included.

Outcome measures

Outcome measures
Measure	Arm I n=9 Participants Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11.
6-Month and 1-Year Survival: Patients Who Did Not Derive Clinical Benefit From Study Treatment 6-Month Survival	44 percentage of patients
6-Month and 1-Year Survival: Patients Who Did Not Derive Clinical Benefit From Study Treatment 1-Year Survival	11 percentage of patients

Adverse Events

Arm I

Serious events: 4 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm I n=20 participants at risk Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11.
Nervous system disorders aseptic vasculitis	5.0% 1/20 • Number of events 1
Vascular disorders cerebrovascular accident	5.0% 1/20 • Number of events 1
Nervous system disorders meningitis	5.0% 1/20 • Number of events 1
Renal and urinary disorders renal insufficiency	5.0% 1/20 • Number of events 1

Other adverse events

Other adverse events
Measure	Arm I n=20 participants at risk Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11.
Blood and lymphatic system disorders Anemia	75.0% 15/20
Blood and lymphatic system disorders Leukopenia	25.0% 5/20
Infections and infestations Neutropenia	25.0% 5/20
Skin and subcutaneous tissue disorders thrombocytopenia	70.0% 14/20
Gastrointestinal disorders Dehydration	15.0% 3/20
Nervous system disorders dizziness	20.0% 4/20
General disorders Edema	25.0% 5/20
Metabolism and nutrition disorders Elevated alkaline phosphatase	15.0% 3/20
Metabolism and nutrition disorders Elevated AST/ALT	35.0% 7/20
Metabolism and nutrition disorders Elevated creatinine	15.0% 3/20
General disorders Fatigue	90.0% 18/20
Gastrointestinal disorders GI obstruction	0.00% 0/20
Metabolism and nutrition disorders Hyperbilirubinemia	20.0% 4/20
Cardiac disorders Hypertension	20.0% 4/20
Gastrointestinal disorders Nausea	55.0% 11/20
General disorders Pain (all sites)	45.0% 9/20
Skin and subcutaneous tissue disorders Rash/ulceration	20.0% 4/20
Nervous system disorders Sensory neuropathy	30.0% 6/20
Gastrointestinal disorders Vomiting	35.0% 7/20

Additional Information

Assistant Professor, Medical Oncology

Fox Chase Cancer Center

Phone: 215-214-1676

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60