Clinical Trials Register

Summary
EudraCT Number:	2019-003916-29
Sponsor's Protocol Code Number:	TREASURE
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-03-30
Trial 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

Germany - PEI

A.2

EudraCT number

2019-003916-29

A.3

Full title of the trial

- TREASURE-
Thoracic RadiothErapy with Atezolizumab in Small cell lUng canceR Extensive disease: a randomized, open-label, multicenter phase II study

A.3.1

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

- TREASURE-
Thoracic RadiothErapy with Atezolizumab in Small cell lUng canceR Extensive disease

A.3.2

Name or abbreviated title of the trial where available

TREASURE

A.4.1

Sponsor's protocol code number

TREASURE

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04462276

A.5.4

Other Identifiers

Name:	Roche Code	Number:	ML41633
Name:	AIO Study Number	Number:	AIO-TRK-0320
Name:	IKF trial ID	Number:	IKF-t023

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	Frankfurter Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Roche Pharma AG
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Frankfurter Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
B.5.2	Functional name of contact point	Project Management
B.5.3	Address:
B.5.3.1	Street Address	Steinbacher Hohl 2-26
B.5.3.2	Town/ city	Frankfurt
B.5.3.3	Post code	60385
B.5.3.4	Country	Germany
B.5.4	Telephone number	+496976014420
B.5.5	Fax number	+496976013655
B.5.6	E-mail	treasure@ikf-khnw.de

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® 1.200 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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.3.4	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.3.11 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	No
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.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Small cell lung cancer extensive disease

E.1.1.1

Medical condition in easily understood language

Small cell lung cancer extensive disease

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	21.1
E.1.2	Level	PT
E.1.2	Classification code	10041068
E.1.2	Term	Small cell lung cancer extensive stage
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

The objective of this study is to investigate the treatment efficacy of combining thoracic radiotherapy (TRT) with the IMpower133 regimen in the upfront treatment of ED SCLC patients.
The study is designed in an attempt to increase the efficacy of atezolizumab maintenance after induction with chemo/atezolizumab by adding radiotherapy.

E.2.2

Secondary objectives of the trial

Additionally, with this study, we aim to determine the safety and tolerability of the combination of immunological and radiological treatment in the first-line setting of advanced SCLC.
Furthermore, we aim to collect blood, stool and tissue samples prospectively for the separate translational program.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Fully-informed written consent and locally required authorization (European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
2. Age ≥ 18 years.
3. Histologically or cytologically confirmed ED SCLC as defined according to the Veterans Administration Lung Study Group staging system.
4. Measurable ED SCLC according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. In cases of CR or PR without residual measurable disease after 4 cycles of induction therapy, patients may still be included. In such cases “No Evidence of Disease (NED)” should be reported in eCRF.
5. ECOG performance-status score of 0 or 1 at screening
6. Any response after four cycles of standard chemo-immunotherapy (carboplatin, etoposide, atezolizumab) defined as CR/PR or thoracic SD with CR/PR of extrathoracic lesions as per RECIST 1.1
7. Thoracic treatment volume considered treatable using acceptable radiation fields as judged by a radiation oncologist
8. 28 ± 7 days between last administration of chemo-immunotherapy (carboplatin, etoposide, atezolizumab) and randomization.
9. Patients with a history of treated CNS metastases are eligible, if there is no ongoing requirement for corticosteroids as therapy for CNS disease. Before randomization, MRI of brain (with contrast, unless contraindicated) is recommended in subjects with suspected or known brain metastases, as per local standard., Patients with asymptomatic brain metastases that do not require local therapy with irradiation (whole brain irradiation) can be included. In ambiguous cases, consultation with the LKP or his/her delegate is advised.
10. No previous radiotherapy to thorax lung and mediastinal lymph nodes within the past 5 years before the first dose of study drug
11. Availability of pre-treatment tumor tissue specimen
12. The patient is willing and able to comply with the protocol for the duration of the study, including hospital visits for treatment and scheduled follow-up visits and examinations.
13. FEV1 ≥ 40% (%Soll)
14. Adequate bone marrow and renal function including the following:
• Hemoglobin ≥ 9.0 g/dL;
• Absolute neutrophil count ≥ 1.0 x 10^9/L;
• Platelets ≥75x 10^9/L;
• Calculated creatinine clearance ≥30 mL/min as determined by the Cockcroft-Gault equation
15. Adequate hepatic function (with stenting for any obstruction, if required) including the following:
• Serum bilirubin ≤ 3 x institutional upper limit of normal (ULN);
• AST (SGOT) / ALT (SGPT) and alkaline phosphatase ≤ 2.5x ULN
Following exceptions apply:
• Patients with documented liver metastases: AST and/or ALT ≤ 5x ULN
• Patients with documented liver or bone metastases: alkaline phosphatase ≤ 5x ULN.
16. Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.
17. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
• Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
• Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).

E.4

Principal exclusion criteria

1. Previous treatment with CD137 agonists, immune-checkpoint blockade therapies, anti-PD-1, or anti-PD-L1 therapeutic antibodies (with the exclusion of prior immunotherapy as defined in inclusion criterion 6).
2. Prior therapy for limited-stage SCLC with curative intent.
3. Prior radiotherapy of lung and mediastinal lymph nodes within the past 5 years before the first dose of study drug.
4. Oxygen-dependent medical condition.
5. History or current radiology suggestive of interstitial lung disease (ILD) (including but not limited to idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP)/cryptogenic fibrosing alveolitis (CFA)), non-infectious pneumonitis, drug-induced pneumonitis, idiopathic pneumonitis.
6. Criterion removed.
7. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study, or during the follow-up period of an interventional study.
8. Participation in another clinical study with an investigational product within 21 days prior to the first dose of the study treatment.
9. Any concurrent chemotherapy, investigational product (IMP), biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer related conditions (e.g. hormone replacement therapy) is acceptable.
10. Major surgery (as defined by the Investigator) within 4 weeks prior to enrollment into the study; patients must have recovered from effects of any major surgery. Note: Local non-major surgery for palliative intent is acceptable.
11. Active or prior documented autoimmune or inflammatory disorders (including but not limited to diverticulitis [with the exception of diverticulosis], celiac disease, systemic lupus erythematosus, Sarcoidosis, or Wegener’s syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis). The following are exceptions to this criterion:
o Patients with vitiligo or alopecia
o Patients with hypothyroidism (e.g., following Hashimoto’s disease) stable on hormone replacement
o Patients with controlled Type I diabetes mellitus on an insulin regimen
o Any chronic skin condition that does not require systemic therapy
o Patients without active disease in the last 5 years may be included but only after consultation with the study physician.
12. Active, uncontrolled inflammatory bowel disease [e.g. ulcerative colitis or Crohn's disease]. Patients in stable remission for more than 1 year may be included.
13. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, interstitial lung disease, gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
14. History of another primary malignancy except for:
o Malignancy treated with curative intent and with no known active disease ≥ 3 years before the first dose of IMP and of low potential risk for recurrence
o Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
o Adequately treated carcinoma in situ without evidence of disease
15. History of active primary immunodeficiency
16. History of allogenic organ or tissue transplantation.
17. Clinical diagnosis of active tuberculosis.
18. Positive testing for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
19. Positive testing for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
20. Current or prior use of immunosuppressive medication within 14 days before the first dose of atezolizumab. The following are exceptions to this criterion:
o Intranasal, inhaled, topical steroids, or local steroid injections (e.g. intra articular injection)
o Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
o Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication)
21. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 5 months after the last dose of atezolizumab monotherapy.
22. Known allergy or hypersensitivity to the IMP or any of the constituents of the product.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is overall survival (OS), defined as time from randomization to death due to any cause. The primary endpoint will be evaluated as a time-to-event variable using a Cox proportional hazards model.

E.5.1.1

Timepoint(s) of evaluation of this end point

at study end / after LVLS

E.5.2

Secondary end point(s)

• 1- and 2-year OS rate
• PFS (according to RECIST 1.1 and iRECIST)
• Response rate (according to RECIST 1.1 and iRECIST)
• Disease control rate (according to RECIST 1.1 and iRECIST)
• Intrathoracic tumor control (defined as the time to intrathoracic progression which is defined as time from randomization until an intrathoracic progression according to RECIST 1.1)
• Extrathoracic tumor control (defined as the time to extrathoracic progression which is defined as time from randomization until extrathoracic progression according to RECIST 1.1).
• Safety in terms of
- Incidence, nature, causal relationship and severity of Adverse Events according to NCI CTCAE v5.0
- Frequency of abnormal laboratory parameters
• Feasibility in terms of:
- frequency of treatment withdrawal (either due to adverse events or other reasons)
- completion of radiotherapy
• Cancer related quality of life (FACT-L)
• Collection of biomarker samples for separate biomarker research project

E.5.2.1

Timepoint(s) of evaluation of this end point

• all secondary endpoints will be finally evaluated at study end (after LVLS)
• 1- and 2-year OS rate: additionally at 1 and 2 years after LPI
• Safety will be evaluated continously and after LVLS

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Atezolizumab maintenance without thoracic radiotherapy

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

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

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

LVLS

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

E.8.9.2

In all countries concerned by the trial days

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

104

F.4.2.2

In the whole clinical trial

104

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)

None.

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

2020-06-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-06-25

P. End of Trial
P.	End of Trial Status	Ongoing

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