tailOred dRug repurposIng of dEcitabine in KRAS-dependeNt refracTory pAncreaTic cancEr

NCT05360264 | Terminated Phase 2 FDA Drug

• 2 other identifiers: IFO21_022021-002632-23
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 6

Brief Summary

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

Conditions

Pancreatic Adenocarcinoma Metastatic; Pancreatic Adenocarcinoma Recurrent

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Disease Control Rate (DCR)

  Every 8 weeks (±1 week) from enrolment for the first 40 weeks, then every 12 weeks (±1 week) up to discontinuation the treatment

• Clinical Benefit Rate (CBR)

  Every 8 weeks (±1 week) from enrolment for the first 40 weeks, then every 12 weeks (±1 week) up to discontinuation the treatment

• tumor marker (Ca19.9) response

  On day 1 of every cycle and at the treatment discontinuation

• Number of participants with treatment-related adverse events as assessed by 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.

• PFS (progression free survival)

  Every 8 weeks (±1 week) from enrolment for the first 40 weeks, then every 12 weeks (±1 week) and at the treatment discontinuation

Study Arms (1)

Experimental group

EXPERIMENTAL

A fresh, mandatory, tumor biopsy will be performed at baseline to assess KRAS mutational status and functional dependency and determine the patient's eligibility for the trial. KRAS dependency will be assessed based on computational score and inferred by a transcriptional signature of tumor cells. Transcriptomic data will be generated by using RNAseq data. Sample RNA processing and generation of the gene expression profile will be guaranteed within a maximum of 10 working days from the biopsy. Patients with high L-, S- or both L/S- scores of KRAS-dependency will receive DACOGEN. DACOGEN will be administered i.v. over 1 hour, at the dose of 10 mg/m2/d, daily on days 1-5 and 8-12 of each 4-wk cycle. Patients will continue to receive study treatment until objective radiological disease progression per modified RECIST 1.1, as assessed by the investigator, unacceptable toxicity, physician's decision, patient's refusal, or until they meet any other discontinuation criteria.

Drug: Decitabine 50 MG [Dacogen]

Interventions

Decitabine 50 MG [Dacogen] DRUG

DACOGEN will be administered i.v. over 1 hour, at the dose of 10 mg/m2/d, daily on days 1-5 and 8-12 of each 4-wk cycle.

Also known as: Dacogen

Experimental group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years;
• Histologically or cytologically proven, advanced, inoperable (metastatic or locally advanced), PDAC;
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2;
• Life expectancy of at least 12 weeks;
• At least one and no more than two lines of systemic treatment for advanced disease;
• At least one metastatic lesion(s) and/or primary tumor amenable to pre-treatment biopsy;
• KRAS dependency, as assessed by molecular analysis of RNA isolated from a fresh tumor biopsy;
• Imaging-documented progressive disease (PD), according to modified RECIST 1.1 criteria;
• Imaging-documented measurable disease, according to modified RECIST 1.1 criteria;
• Adequate organ and marrow function;
• Postmenopausal status or evidence of non-childbearing status (negative urine or serum pregnancy test) for women of childbearing potential;
• 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

You may not qualify if:

• Uncontrolled intercurrent illness(es);
• Pregnancy or lactation;
• Active and uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy;
• Major surgical intervention within 4 weeks prior to enrollment;
• Radiotherapy, surgery, chemotherapy, or an investigational therapy within 2 weeks prior to signing the treatment ICF;
• Any previous treatment with DEC;
• 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;
• Persistent toxicities (≥CTCAE grade 2) caused by previous cancer therapy, excluding alopecia;
• 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;
• Serious psychiatric or medical conditions that could interfere with a valid informed consent.

Sponsors & Collaborators

• Luca Cardone: lead
• Anticancer Fund, Belgium: collaborator
• Azienda Ospedaliera Universitaria Integrata Verona: collaborator
• Catholic University of the Sacred Heart: collaborator
• Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale: collaborator
• San Raffaele University Hospital, Italy: collaborator
• University of Pisa: collaborator

Study Sites (6)

Irccs S. Raffaele - Milano

Milan, Italy

Location

Istituto Nazionale Tumori Di Napoli Irccs Pascale

Napoli, Italy

Location

Azienda Ospedaliero-Universitaria Pisana

Pisa, Italy

Location

Istituti Fisioterapici Ospitalieri- Ifo - Istituto Regina Elena

Rome, 00015, Italy

Location

Policlinico A. Gemelli E C.I.C.- Policlinico Universitario A. Gemelli

Rome, Italy

Location

Az.Osp.Universitaria Integrata Verona- Borgo Roma

Verona, Italy

Location

MeSH Terms

Interventions

Decitabine

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• LUCA CARDONE, PhD

  ISTITUTI FISIOTERAPICI OSPITALIERI- IFO - ISTITUTO REGINA ELENA

  PRINCIPAL INVESTIGATOR

• Michele Milella, Prof.

  AZ.OSP.UNIVERSITARIA INTEGRATA VERONA- BORGO ROMA 05091202

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Single Group Assignment

Study Record Dates

• First Submitted: April 6, 2022
• First Posted: May 4, 2022
• Study Start: January 15, 2022
• Primary Completion: October 10, 2024
• Study Completion: October 10, 2024
• Last Updated: March 24, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (6)