A Phase 3 Study to compare how effective and safe DCC-2618 is versus sunitinib in patients with GIST who have been treated previously with imatinib

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Deciphera Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 May 2019 → ongoing

Decision date (initial)

2024-10-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Deciphera Pharmaceuticals, LLC

External identifiers

EU CT number

2024-513277-52-00

EudraCT number

2018-001803-35

ClinicalTrials.gov

NCT03673501

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Pharmacogenomic, Efficacy, Pharmacokinetic

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 previously received first-line therapy with imatinib

Secondary objectives 2

1. To assess objective response rate (ORR) by independent radiologic review using mRECIST criteria
2. To assess Overall Survival (OS)

Conditions and MedDRA coding

Patients with Advanced Gastrointestinal Stromal Tumors

Regulatory references

Scientific advice from competent authorities

European Medicines Limited

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Patients ≥ 18 years of age at the time of informed consent.
2. Histologic diagnosis of GIST and must be able to provide an archival tumor tissue sample, otherwise, a fresh biopsy is required.
3. Molecular pathology report with mutational status of KIT/PDGFRA must be available. Mutation status must be identified by using a tissue-based PCR/sequencing assay. Molecular pathology report with mutation status of KIT/PDGFRA must be provided to the Sponsor for review prior to randomization. If molecular pathology report is not available or insufficient, an archival tumor tissue sample or fresh biopsy is required for mutation status confirmation by the central laboratory prior to randomization.
4. Patients must have progressed on imatinib or have documented intolerance to imatinib. Imatinib treatment must have been discontinued 10 days prior to the first dose of study drug. All prior imatinib treatment will count as one line of therapy (e.g. adjuvant imatinib and dose escalation of imatinib).
5. Eastern Cooperative Oncology Group (ECOG) PS of ≤ 2 at screening.

Exclusion criteria 5

1. imatinib for advanced GIST. Imatinib-containing combination therapy in the first line setting is not allowed.
2. Patients with a prior or concurrent malignancy whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of this clinical trial are not eligible. For example, patients receiving adjuvant cancer treatment are not eligible if those medications are potentially active against GIST or excluded per protocol. NOTE: Patients with a history of breast cancer, requiring continued hormonal treatment (e.g. anti-estrogen or an aromatase inhibitor) may continue treatment. Patients with a history of prostate cancer, requiring continued support with luteinizing hormone releasing hormone (LHRH) agonists, with or without androgens, may continue treatment. NOTE: Patients may not be part of an ongoing or Have prior participation in an investigational drug Study within 30 days of screening.
3. Patient has known active central nervous system metastases.
4. New York Heart Association class II-IV heart disease, myocardial infarction within 6 months of cycle 1 day 1, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart failure.
5. Left ventricular ejection fraction (LVEF) < 50% at screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS of DCC-2618 based on independent radiologic review using mRECIST criteria.

Secondary endpoints 3

1. Efficacy • ORR (confirmed CR + confirmed PR) based on independent radiologic review using mRECIST criteria • OS The primary and secondary endpoints will be analyzed for both the KIT Exon 11 (Exon 11 ITT) and the All Patients (AP ITT) population.
2. Safety Safety endpoints that will be evaluated include treatment-emergent adverse events (TEAEs), SAEs, 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.
3. Pharmacokinetics • Correlation of PK exposure with efficacy/safety • Population-based PK parameters

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Deciphera Pharmaceuticals Inc.

Sponsor organisation

Deciphera Pharmaceuticals Inc.

Address

200 Smith Street

City

Waltham

Postcode

02451-0099

Country

United States

Scientific contact point

Organisation

Deciphera Pharmaceuticals Inc.

Contact name

Clinical trial information

Public contact point

Organisation

Deciphera Pharmaceuticals Inc.

Contact name

Clinical trial information

Third parties 13

Locations

5 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 34 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications