Clinical Trials Register

Summary
EudraCT Number:	2017-002446-76
Sponsor's Protocol Code Number:	DCC-2618-03-001
National Competent Authority:	Finland - Fimea
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-03-21
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

Finland - Fimea

A.2

EudraCT number

2017-002446-76

A.3

Full title of the trial

A Phase 3, INterVentional, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of DCC-2618 In Patients with AdvanCed Gastrointestinal Stromal TUmorS who have Received Treatment with Prior Anticancer Therapies

A.3.1

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

A Phase 3 study of DCC-2618 versus placebo in patients with advanced Gastrointestinal Stromal Tumors (GIST) to learn more about the safety of DCC-2618 and how well it works against GIST in patients who have received prior anticancer treatments.

A.3.2

Name or abbreviated title of the trial where available

INVICTUS

A.4.1

Sponsor's protocol code number

DCC-2618-03-001

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	Deciphera Pharmaceuticals, LLC
B.1.3.4	Country	United States
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	Deciphera Pharmaceuticals, LLC
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Deciphera Pharmaceuticals, LLC
B.5.2	Functional name of contact point	Shreya Mehta
B.5.3	Address:
B.5.3.1	Street Address	500 Totten Pond Rd
B.5.3.2	Town/ city	Waltham
B.5.3.3	Post code	02451
B.5.3.4	Country	United States
B.5.4	Telephone number	0017812096415
B.5.6	E-mail	clinicaltrials@deciphera.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	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/17/1936
D.3 Description of the IMP
D.3.1	Product name	DCC-2618
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DCC-2618
D.3.9.1	CAS number	1442472-39-0
D.3.9.2	Current sponsor code	DCC-2618
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with AdvanCed Gastrointestinal Stromal TUmorS

E.1.1.1

Medical condition in easily understood language

Patients with AdvanCed Gastrointestinal Stromal TUmorS

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the efficacy (progression-free survival [PFS]) of DCC-2618 by independent radiologic review in patients with advanced gastrointestinal stromal tumors (GIST) who have received prior therapies

E.2.2

Secondary objectives of the trial

Key Secondary Objective:
• To assess objective response rate by independent radiologic review

Secondary Objectives:
• To assess other parameters of efficacy, including but not limited to time to progression (TTP) and overall survival (OS)
• To assess the PD/PK relationship of DCC-2618
• To assess the robustness of efficacy using a sensitivity analysis
• To assess improvement of disease-related symptoms and quality of life
• To assess the safety of DCC-2618

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female patients ≥18 years of age at the time of informed consent
2. Histologic diagnosis of GIST
3. Patients must have progressed on imatinib, sunitinib, and regorafenib or have documented intolerance to any of these treatments despite dose
modifications.
4. ECOG PS of 0 to 2 at screening.
5. Able to provide an archival tumor tissue sample if no anticancer therapy was administered since the sample was collected; otherwise, a fresh tumor tissue sample is required prior to the first dose of study drug.
6. Female patients of childbearing potential must have a negative serum
beta-human chorionic gonadotrophin (β-hCG) pregnancy test at screening and a negative pregnancy test at Cycle 1 Day 1 prior to the first dose of study drug.
7. Patients of reproductive potential must agree to follow the contraception requirements outlined in Section 6.11.10 of the study protocol.
8. The patient is capable of understanding and complying with the protocol and has signed the informed consent document. A signed informed consent form must be obtained before any study-specific procedures are performed.
9. At least 1 measurable lesion according to modified RECIST Version 1.1 (non-nodal lesions must be ≥1.0 cm in the long axis or ≥double the slide thickness in the long axis) within 21 days prior to the first dose of study drug.
10. Adequate organ function and bone marrow reserve as indicated by the following laboratory assessments performed at screening.
• Absolute neutrophil count ≥1000/μL
• Hemoglobin ≥8 g/dL
• Platelet count ≥75,000/μL
• Total bilirubin ≤1.5 x the upper limit of normal (ULN)
• Aspartate transaminase or alanine transaminase ≤3 x ULN
(≤5x ULN in the presence of hepatic metastases)
• Serum creatinine ≤1.5 x ULN or creatinine clearance ≥50 mL/min based on either urine collection or Cockcroft Gault estimation.
• Prothrombin time (PT) or international normalized ratio (INR) or partial thromboplastin time ≤1.5 x ULN. Patients on a stable, maintenance regimen of anticoagulant therapy for at least 30 days prior to study drug administration may have PT/INR measurements >1.5 x ULN if, in the opinion of the Investigator, the patient is
suitable for the study. An adequate rationale must be provided to the Sponsor prior to randomization.
11. Resolution of all toxicities from prior therapy to ≤Grade 1 (or baseline) within 1 week prior to the first dose of study drug (excluding alopecia and ≤Grade 3 clinically asymptomatic lipase, amylase, and creatine phosphokinase laboratory abnormalities).

E.4

Principal exclusion criteria

1. Treatment with anticancer therapy, including investigational therapy, or investigational procedures within 14 days or 5 x the half-life (whichever is longer) prior to the first dose of study drug. For prior biological therapies, eg, monoclonal antibodies with a half-life longer than 3 days, the interval must be at least 28 days prior to the first dose of study drug.
2. Prior treatment with DCC-2618
3. Prior or concurrent malignancy whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of DCC-2618.
Patients receiving adjuvant cancer treatment are not eligible if those medications are potentially active against GIST or excluded per protocol (refer to Section 5.12.3 of the protocol).
4. Has a known additional malignancy that is progressing or required active treatment within 3 years of the first dose of study drug. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or other in situ cancers.
5. Patient has known active central nervous system metastases.
6. New York Heart Association class II - IV heart disease, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart failure.
7. Arterial thrombotic or embolic events such as cerebrovascular accident (including ischemic attacks) or hemoptysis within 6 months before the first dose of study drug.
8. Venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg, pulmonary embolism) within 3 months before the first dose of study drug. Patients with venous thrombotic events ≥3 months before the first dose of study drug on stable anticoagulation therapy are eligible.
9. 12-lead electrocardiogram (ECG) demonstrating QT interval corrected by Fridericia’s formula >450 ms in males or >470 ms in females at screening or history of long QT interval corrected syndrome.
10. Left ventricular ejection fraction (LVEF) <50% at screening.
11. Use of proton-pump inhibitors within 4 days prior to the first dose of study drug. Other medications that increase gastric pH, ie, histamine H2 receptor antagonists and antacids may be taken provided they are not administered within 2 hours before or after administration of study drug.
12. Use of strong or moderate inhibitors and inducers of cytochrome P450 (CYP) 3A4, including certain herbal medications (eg, St. John’s Wort) and consumption of grapefruit or grapefruit juice within 14 days or 5 x the half-life (whichever is longer) prior to the first dose of study drug. Please refer to the Indiana University Department of Medicine website (http://medicine.iupui.edu/clinpharm/ddis/main-table/) for guidance on
medications that inhibit CYP3A4 enzymes.
13. Use of known substrates or inhibitors of breast cancer resistance protein (BCRP) transporters within 14 days or 5 x the half-life (whichever is longer) prior to the first dose of study drug. Please refer to the US Food and Drug Administration’s (FDA) website(http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm) for inhibitors and substrates.
14. Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug. Following major surgeries, >4 weeks prior to the first dose of study drug, all surgical wounds must be healed and free of infection or dehiscence.
15. Any other clinically significant comorbidities, such as uncontrolled pulmonary disease, active infection, or any other condition, which in the judgment of the Investigator, could compromise compliance with the protocol, interfere with interpretation of the study results, or predispose the patient to safety risks.
16. Known human immunodeficiency virus or hepatitis C infection only if the patient is taking medications that are excluded per protocol (refer to Section 5.12.3 of the study protocol), active hepatitis B, or active hepatitis C infection.
17. If female, the patient is pregnant or lactating.
18. Known allergy or hypersensitivity to any component of the investigational drug product.
19. Any active bleeding excluding hemorrhoidal or gum bleeding.

E.5 End points

E.5.1

Primary end point(s)

PFS based on independent radiologic review using modified RECIST (1; Appendix 17.1 of the protocol). Modified RECIST criteria includes:
• No lymph nodes chosen as target lesions; enlarged lymph nodes followed as non-target lesions;
• No bone lesions chosen as target lesions;
• Positron emission tomography not acceptable for radiological evaluation;
• A progressively growing new tumor nodule within a pre-existing tumor mass must meet the following criteria to be considered as unequivocal evidence of progression according to the modification of RECIST Version 1.1: (a) the lesion is at least 2 cm in size and definitively a new active GIST lesion (eg, enhancing with contrast or other criteria to rule out artefact); or (b) the lesion has to be expanding on at least 2 sequential imaging studies.

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary endpoint of PFS (reported in weeks) is defined as the interval between the date of randomization and the earliest documented evidence of disease progression based on the independent radiologic review, or death due to any cause. Patients who undergo surgical resection of target or non-target lesions, who have received other anticancer treatments, or patients who do not have a documented date of progression or death due to any cause will be censored at the date of the last assessment. Analysis for PFS will be un-stratified.

E.5.2

Secondary end point(s)

Key Secondary Efficacy Endpoint:
• Objective response rate (confirmed CR + confirmed PR)

Secondary Efficacy Endpoints:
• TTP based on independent radiologic review
• OS
• Time to best response
• PFS based on Investigator assessment
• Quality of life as determined by changes from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer 30-item and EuroQol 5-Dimension 5-Level
• Disease control rate (complete response [CR] + partial response [PR] + stable disease) at 12 weeks

Safety:
Treatment-emergent adverse events, adverse events of special interest, serious adverse events, dose reduction or discontinuation of study drug due to toxicity; and changes from baseline in ECOG PS, vital signs, ECGs, LVEF, dermatologic examinations, and clinical laboratory parameters.

Pharmacokinetics (PK):
• Correlation of PK with efficacy/safety
• Population PK

E.5.2.1

Timepoint(s) of evaluation of this end point

Objective response rate: to be assigned a status of a CR or PR, changes in tumor measurements must be confirmed by repeat assessments that must be performed at least 4 weeks after the criteria for response are first met. Patients with unknown or missing response will be treated as non responders, that is, they will be included in the denominator when calculating the proportion. Time to confirmed response (CR or PR) (reported in weeks) is defined as the interval between the date of first dose of study medication and the earliest date of first documented confirmed CR or confirmed PR. Patients who do not have a confirmed PR or CR will be censored at the date of the last adequate assessment.

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

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

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

E.8.1.6

Cross over

Yes

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

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

Yes

E.8.4

The trial involves multiple sites in the 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

Australia

Belgium

Canada

Finland

France

Germany

Italy

Netherlands

Poland

Singapore

Spain

United Kingdom

United States

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

F.4.2.2

In the whole clinical trial

120

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)

Return to standard of care

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

2018-04-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-03-28

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-05-11

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