Pancreatic Adenocarcinoma Metastatic Clinical Trial
— ORIENTATEOfficial title:
A Proof-of-concept, Biomarker-driven, Phase-II Clinical Trial to Explore the Activity of Decitabine Repurposing Against Advanced, Refractory, KRAS-dependent Pancreatic Ductal Adenocarcinoma (PDAC):The ORIENTATE Trial
The study is designed to assess the therapeutic efficacy of decitabine repurposing against advanced, refractory, ductal adenocarcinoma (PDAC) with molecular transcriptional signatures indicating dependency on the KRAS oncogene
Status | Recruiting |
Enrollment | 18 |
Est. completion date | February 2025 |
Est. primary completion date | February 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. Age = 18 years; 2. Histologically or cytologically proven, advanced, inoperable (metastatic or locally advanced), PDAC; 3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2; 4. Life expectancy of at least 12 weeks; 5. At least one and no more than two lines of systemic treatment for advanced disease; 6. At least one metastatic lesion(s) and/or primary tumor amenable to pre-treatment biopsy; 7. KRAS dependency, as assessed by molecular analysis of RNA isolated from a fresh tumor biopsy; 8. Imaging-documented progressive disease (PD), according to modified RECIST 1.1 criteria; 9. Imaging-documented measurable disease, according to modified RECIST 1.1 criteria; 10. Adequate organ and marrow function; 11. Postmenopausal status or evidence of non-childbearing status (negative urine or serum pregnancy test) for women of childbearing potential; 12. Women of childbearing potential (defined as not post- menopausal for 12 months or no previous surgical sterilization) and fertile men must agree to use two highly effective forms of contraception while they are receiving Exclusion Criteria: 1. Uncontrolled intercurrent illness(es); 2. Pregnancy or lactation; 3. Active and uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy; 4. Major surgical intervention within 4 weeks prior to enrollment; 5. Radiotherapy, surgery, chemotherapy, or an investigational therapy within 2 weeks prior to signing the treatment ICF; 6. Any previous treatment with DEC; 7. Patients with second primary cancers, except for adequately treated non- melanoma skin cancer, curatively treated in-situ cancer of the cervix, stage 1 grade 1 endometrial carcinoma, or other solid tumours including lymphomas (without bone marrow involvement) treated with curative intent and with no evidence of active disease at >1 year from the completion of curative treatment prior to study entry; 8. Persistent toxicities (=CTCAE grade 2) caused by previous cancer therapy, excluding alopecia; 9. Serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug; 10. Serious psychiatric or medical conditions that could interfere with a valid informed consent. |
Country | Name | City | State |
---|---|---|---|
Italy | Irccs S. Raffaele - Milano | Milano | |
Italy | Istituto Nazionale Tumori Di Napoli Irccs Pascale | Napoli | |
Italy | Azienda Ospedaliero-Universitaria Pisana | Pisa | |
Italy | Istituti Fisioterapici Ospitalieri- Ifo - Istituto Regina Elena | Rome | |
Italy | Policlinico A. Gemelli E C.I.C.- Policlinico Universitario A. Gemelli | Rome | |
Italy | Az.Osp.Universitaria Integrata Verona- Borgo Roma | Verona |
Lead Sponsor | Collaborator |
---|---|
Luca Cardone | Anticancer Fund, Belgium, Azienda Ospedaliera Universitaria Integrata Verona, Catholic University of the Sacred Heart, Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale, San Raffaele University Hospital, Italy, University of Pisa |
Italy,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Best Overall Respone (BOR) according to RECIST1.1 | Best response is recorded from the start of the treatment until disease progression. Tumor assessments according to modified RECIST 1.1 criteria will be performed at baseline and every 8 weeks (±1week) up to 40 weeks and then every 12 weeks (±1 week) until objective radiological disease progression according to modified RECIST criteria (evised RECIST guideline (version 1.1). Eur J Cancer 2009. DOI:10.1016/j.ejca.2008.10.026). | From registration to date of documented best response, assessed up to 24 months | |
Secondary | Disease Control Rate (DCR) | The percentage of patients who have achieved complete response, partial response and stable disease according to modified RECIST 1.1 | Every 8 weeks (±1 week) from enrolment for the first 40 weeks, then every 12 weeks (±1 week) up to discontinuation the treatment | |
Secondary | Clinical Benefit Rate (CBR) | CBR is a multidimensional endpoint encompassing performance status, pain, and weight loss/gain | Every 8 weeks (±1 week) from enrolment for the first 40 weeks, then every 12 weeks (±1 week) up to discontinuation the treatment | |
Secondary | tumor marker (Ca19.9) response | Tumor marker response is defined as percent reduction of CA19.9 at nadir, as compared to baseline levels and will be evaluated only in patients with elevated CA19.9 levels at baseline. | On day 1 of every cycle and at the treatment discontinuation | |
Secondary | Number of participants with treatment-related adverse events as assessed by CTCAE version 5.0 | Monitored throughout the study and will be assessed and graded according to CTCAE (version 5.0) | Adverse Events will be collected from time of signature of informed consent throughout the treatment period up to and including the 30-day follow-up period. | |
Secondary | PFS (progression free survival) | PFS will be calculated form treatment start until progression or death. | Every 8 weeks (±1 week) from enrolment for the first 40 weeks, then every 12 weeks (±1 week) and at the treatment discontinuation | |
Secondary | OS (overall survival) | OS will be calculated from treatment start until progression or death. | Every 8 weeks (±1 week) from enrolment for the first 40 weeks, then every 12 weeks (±1 week) and at the treatment discontinuation |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT06006728 -
Real World Efficacy, Safety of Nanoliposomal Irinotecan With Fluorouracil and Folinic Acid in Metastatic Pancreatic Cancer After Previous Gemcitabine-based Therapy
|
||
Terminated |
NCT03213626 -
Cabozantinib and Erlotinib for Patients With EGFR and c-Met Co-expressing Metastatic Pancreatic Adenocarcinoma
|
Phase 2 | |
Recruiting |
NCT05077800 -
FOLFIRINOX + 9-Ing-41 + Losartan In Pancreatic Cancer
|
Phase 2 | |
Completed |
NCT01715142 -
Effect on Tumor Perfusion of a Chemotherapy Combining Gemcitabine and Nab-paclitaxel (Abraxane) in Pancreatic Cancer
|
Early Phase 1 | |
Completed |
NCT02179970 -
To Assess the Safety of Continuous IV Administration of Plerixafor in Patients With Advanced Pancreatic, Ovarian and Colorectal Cancers
|
Phase 1 | |
Completed |
NCT02195180 -
Efficacy and Safety of L-asparaginase Encapsulated in RBC Combined With Gemcitabine or FOLFOX in 2nd Line for Progressive Metastatic Pancreatic Carcinoma
|
Phase 2 | |
Recruiting |
NCT06051851 -
Penpulimab Combined With Anlotinib and Nab-paclitaxel Plus Gemcitabine as First-line Treatment for Advanced Metastatic Pancreatic Cancer
|
Phase 2 | |
Recruiting |
NCT03633734 -
Efficacy Evaluation of Sequential Treatment With AG and Modified Folfirinox in Metastatic Pancreatic Adenocarcinoma
|
Phase 1/Phase 2 | |
Completed |
NCT03529175 -
Scheduling Nab-paclitaxel With Gemcitabine
|
Phase 2 | |
Recruiting |
NCT04150042 -
SHARON: A Clinical Trial for Metastatic Cancer With a BRCA or PALB2 Mutation Using Chemotherapy and Patients' Own Stem Cells
|
Phase 1 | |
Withdrawn |
NCT03127124 -
QUILT-2.022 NANT-008 in Combination w/ 5-fluorouracil, Bevacizumab, Leucovorin & Oxaliplatin in Subjects With Pancreatic Cancer
|
Phase 1/Phase 2 | |
Not yet recruiting |
NCT06076837 -
The Seven Trial: Exploiting the Unfolded Protein Response
|
Phase 1 | |
Recruiting |
NCT06396637 -
PD-1 Antibody and Sapropterin Dihydrochloride in Patients With PDAC
|
Phase 2 | |
Completed |
NCT01053013 -
Open-Label Phase 2 Efficacy Trial of Cancer Macrobeads in Patients With Treatment-Resistant Pancreatic/Colorectal Cancer
|
Phase 2 |