Clinical Trials Register

Summary
EudraCT Number:	2020-003759-14
Sponsor's Protocol Code Number:	GO42661
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-11-23
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2020-003759-14

A.3

Full title of the trial

A PHASE II, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF ATEZOLIZUMAB WITH OR WITHOUT BEVACIZUMAB IN COMBINATION WITH
CISPLATIN PLUS GEMCITABINE IN PATIENTS WITH UNTREATED, ADVANCED BILIARY TRACT CANCER

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Study of Atezolizumab with or Without Bevacizumab in Combination with Cisplatin Plus Gemcitabine in Patients with Advanced Biliary Tract Cancer

A.4.1

Sponsor's protocol code number

GO42661

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	F. Hoffman-La Roche Ltd.
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	F. Hoffmann-La Roche Ltd.
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	F.Hoffmann-La Roche Ltd.
B.5.2	Functional name of contact point	Trial Information Support Line-TISL
B.5.3	Address:
B.5.3.1	Street Address	Grenzacherstrasse 124
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4070
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+4161 688 1111
B.5.5	Fax number	+4161 691 9319
B.5.6	E-mail	global.rochegenentechtrials@roche.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Tecentriq
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Products GmbH
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Atezolizumab
D.3.2	Product code	RO5541267/F03
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ATEZOLIZUMAB
D.3.9.1	CAS number	1380723-44-3
D.3.9.2	Current sponsor code	RO5541267
D.3.9.3	Other descriptive name	MPDL3280A, Tecentriq
D.3.9.4	EV Substance Code	SUB178312
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	60
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Avastin
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Bevacizumab
D.3.2	Product code	RO4876646/F02
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BEVACIZUMAB
D.3.9.1	CAS number	216974-75-3
D.3.9.2	Current sponsor code	RO4876646
D.3.9.3	Other descriptive name	rhuMAb VEGF, anti-VEGF
D.3.9.4	EV Substance Code	SUB178312
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	Recombinant humanised monoclonal antibody

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Concentrate for solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Biliary tract cancer

E.1.1.1

Medical condition in easily understood language

Biliary tract cancer is a rare type of cancer that occurs in a bile duct. Patients with advanced biliary tract cancer generally have a poor prognosis.

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10008593
E.1.2	Term	Cholangiocarcinoma
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10001141
E.1.2	Term	Adenocarcinoma
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

•To evaluate the efficacy of atezolizumab (Atezo)+ bevacizumab (Bev)+ cisplatin and gemcitabine (CisGem) compared with Atezo+ placebo (PBO)+CisGem based on progression free survival

E.2.2

Secondary objectives of the trial

•To evaluate the efficacy of Atezo+Bev+CisGem compared with Atezo+PBO+CisGem based on overall survival, confirmed objective response rate, duration of response, disease control rate, time to confirmed deterioration
•To evaluate the safety of Atezo+Bev+CisGem compared with Atezo+PBO+CisGem
•To characterize the pharmacokinetics of atezolizumab when given in combination with bevacizumab and/or gemcitabine/cisplatin
•To evaluate the immune response to atezolizumab

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Age >= 18 years at the time of signing Informed Consent Form
•Ability to comply with the study protocol
•Considered to be eligible to receive platinum-based chemotherapy, in the investigator’s judgment
•Documentation of recurrent/metastatic or locally advanced unresectable disease based on computed tomography (CT) or magnetic resonance imaging (MRI) scans
•Histologically or cytologically confirmed diagnosis of intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer
•No prior systemic therapy (including systemic investigational agents) for advanced biliary tract cancer
•At least one measurable untreated lesion (per RECIST v1.1)
•Adequate biliary drainage with no evidence of ongoing infection
•Availability of a representative tumor specimen that is suitable for determination of PD-L1 status via central testing
•Negative HIV test at screening with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count >= 200/L, and have an undetectable viral load
•Documented virology status of hepatitis, as confirmed by screening hepatitis B virus (HBV) and hepatitis C virus (HCV) tests
•Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
•Life expectancy of > 3 months
•Adequate hematologic and end-organ function
•For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs while they are receiving atezolizumab and bevacizumab and for 5 months after the final dose of atezolizumab and for 6 months after the final dose of bevacizumab, cisplatin or gemcitabine, whichever is later
•For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm during the treatment period and for 6 months after the final dose of bevacizumab, cisplatin or gemcitabine, whichever is later, to avoid exposing the embryo

E.4

Principal exclusion criteria

•Recurrent disease =< 6 months after curative surgery or =< 6 months after the completion of adjuvant therapy
•Prior local regional therapy such as radioembolization
•Combined or mixed hepatocellular/cholangiocarcinoma
•Clinically significant hepatic encephalopathy within the 12 months prior to Day 1 of Cycle 1
•NCI CTCAE Grade >= 2 peripheral neuropathy
•Prior bleeding event due to untreated or incompletely treated esophageal and/or gastric varices within 6 months prior to Day 1 of Cycle 1
•Active or history of autoimmune disease or immune deficiency
•History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
•Significant cardiovascular disease within 3 months prior to Day 1 of Cycle 1, unstable arrhythmia, or unstable angina
•History of malignancy other than BTC within 5 years prior to screening
•Symptomatic, untreated, or actively progressing CNS metastases
•For patients with lung metastases, if one of the following criteria
applies: Large,centrally located pulmonary metastases; Clear tumor
infiltration into the thoracic great vessels seen on imaging; –Clear
cavitation of pulmonary lesions seen on imaging
•Active tuberculosis
•Severe infection within 4 weeks prior to Day 1 of Cycle 1
•Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to Day 1 of Cycle 1
•Prior allogeneic stem cell or solid organ transplantation
•On the waiting list for liver transplantation
•Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
•Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of atezolizumab or within 6 months after the final dose of bevacizumab, cisplatin or gemcitabine
•Co-infection with HBV and HCV
•Uncontrolled or symptomatic hypercalcemia
•History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
•History of allergic reactions to cisplatin or other platinum-containing compounds
•Known hypersensitivity to gemcitabine
•Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or bevacizumab formulations
•Treatment with a live, attenuated vaccine within 4 weeks prior to Day 1 of Cycle 1 or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
•Treatment with investigational therapy within 4 weeks prior to Day 1 of Cycle 1
•Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
•Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to Day 1 of Cycle 1
•Treatment with systemic immunosuppressive medication within 2 weeks prior to Day 1 of Cycle 1 or anticipation of need for systemic immunosuppressive medication during study treatment
•Inadequately controlled arterial hypertension (defined as systolic blood pressure [BP]  150 mmHg and/or diastolic BP  100 mmHg), based on an average of at least three BP readings at two or more sessions
•History of hypertensive crisis or hypertensive encephalopathy
•Significant vascular disease within 6 months prior to Day 1 of Cycle 1
•History of hemoptysis within 1 month prior to Day 1 of Cycle 1
•Evidence of bleeding diathesis or significant coagulopathy
•Current or recent (within 10 days of Day 1 of Cycle 1) use of aspirin (  325 mg/day)or current or recent treatment with dipyramidole, ticlopidine, clopidogrel, and cilostazol
•Current or recent (within 10 days prior to Day 1 of Cycle 1) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purpose
•Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 3 days prior to Day 1 of Cycle 1
•History of abdominal or tracheoesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1 of Cycle 1
•Evidence of abdominal free air that is not explained by paracentesis or recent surgical procedure
•Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
•Major surgical procedure within 4 weeks prior to Day 1 of Cycle 1 or anticipation of need for a major surgical procedure during the study
•History of clinically significant and uncontrolled intra-abdominal inflammatory disease within 6 months prior to Day 1 of Cycle 1, including, but not limited to, peptic ulcer disease, diverticulitis, or colitis
•Chronic daily treatment with a non-steroidal anti-inflammatory drug
•Preexisting renal impairment, myelosuppression, or hearing impairment

E.5 End points

E.5.1

Primary end point(s)

1. Progression free survival

E.5.1.1

Timepoint(s) of evaluation of this end point

1. Up to 5 years

E.5.2

Secondary end point(s)

1. Overall survival
2. Confirmed objective response rate as determined by the investigator according to RECIST v1.1
3. Duration of response as determined by the investigator according to RECIST v1.1
4. Disease control rate as determined by the investigator according to RECIST v1.1
5. Time to confirmed deterioration
6. Incidence and severity of adverse events, with severity determined according to NCI CTCAE v5.0
7. Change from baseline in targeted vital signs
8. Change from baseline in targeted clinical laboratory test results
9. Serum concentration of atezolizumab at specified timepoints
10. Prevalence of ADAs to atezolizumab at baseline and incidence of ADAs to atezolizumab during the study

10. Prevalence of ADAs to atezolizumab at baseline and incidence of ADAs to atezolizumab during the study

E.5.2.1

Timepoint(s) of evaluation of this end point

1-6. Up to 5 years
7-8. Baseline (Day -28 to -1) to 5 years
9-10. Day 1 of Cycle 1, 2, 3, 4, 8, 12, and 16, at treatment discontinuation visit

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Patient reported outcomes

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Canada

China

Hong Kong

Korea, Republic of

Russian Federation

Taiwan

Thailand

Turkey

Ukraine

United States

France

Italy

Poland

Spain

United Kingdom

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of this study is defined as the date at which the last data required for study analysis are collected.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

150

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients will be followed for overall survival. Patients who have progressed or discontinued treatment due to loss of clinical benefit or toxicity can go onto receive standard of care for BTC.
The Sponsor will offer continued access to Roche IMPs (atezolizumab and bevacizumab) free of charge to eligible patients in accordance with the Roche Global Policy on Continued Access to Investigational Medicinal Product.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-01-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-01-21

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-08-25

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