Study on chlorambucil efficacy in patients with metastatic pancreatic adenocarcinoma already undergoing previous chemotherapy treatment and carriers of a BRCA mutation or other mutations concerning the genes involved in DNA repair.
- Conditions
- Patients affected by metastatic pancreatic adenocarcinoma (PDAC).MedDRA version: 20.0Level: PTClassification code 10052747Term: Adenocarcinoma pancreasSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-002949-42-IT
- Lead Sponsor
- OSPEDALE SAN RAFFAELE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 30
1)Pathologically confirmed pancreatic adenocarcinoma
2)Age = 18 years
3)ECOG PS 0-2
4)Stage IV disease
5)Identified genetic aberrations that are associated with homologous recombination deficiency (HRD)
a)Cohort A: Documented mutation in gBRCA1 or gBRCA2 that is predicted to be deleterious or suspected deleterious
b)Cohort B: BRCA1 or BRCA2 mutations that are considered to be of uncertain/unknown significance (VUS)
c)Cohort C: Patients with other identified genetic aberrations that are associated with HRD
6)adequate PFS during previous platinum-based chemotherapy for at least 4 months before progression
7)Screening laboratory values:
Leukocytes > 3000/mmc
Thrombocytes > 150000/mmc
Hemoglobin > 10 g/dl
Creatinine <2.0 times upper normal limit (unless normal creatinine clearance).
Total bilirubin <2.0 times upper normal limit (unless due to Gilbert's syndrome).
Alanine aminotransferase (ALT) <3.0 times upper normal limit
8)Able to take oral medication
9)Progression during or after platinum-based chemotherapy
10)Other prior chemotherapy apart from first-line treatment for pancreatic cancer, are allowed, including maintenance treatment with PARP inhibitors
11) More than 2 weeks since prior chemotherapy end
12) Signed written informed consent
13) QTc <450 msec or QTc <480 msec for patients with bundle branch block
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
1)Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months prior to screening, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities
2)Active and uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
3)Vaccination with vaccines called live”, since this treatment causes a drop of immunity defenses and a serious infection could result fatal.
4)History of seizure, head trauma and treatment with anti-epileptogenic drugs
5)Hypersensitivity to chlorambucil or to any excipients, in particular lactose
6)BRCA-mutated advanced pancreatic cancer who did not undergo maintenance with olaparib after platinum-based chemotherapy
7)Mismatch repair (MMR)/high levels of microsatellite instability (MSI-H), or high levels of tumor mutational burden (TMB) pancreatic cancer who did not undergo immunotherapy with pembrolizumab monotherapy or any other anti-PD1 agent
8)Concomitant PARP inhibitors therapy
9)Life expectancy less than 3 months, in the opinion of the investigator
10)Other past or current malignancy. Subjects who have been free of malignancy for at least 5 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible
11)Symptomatic duodenal stenosis
12) Any significant medical condition laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
13) Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
14) Any condition that confounds the ability to interpret data from the study
15) Any familiar, sociologic or geographic conditions that can potentially interfere with the adhesion to the protocol or to the follow-up
16) Pregnant or nursing. Adequate contraception is defined as oral hormonal birth control, intrauterine device, and male partner sterilization
17) Concurrent treatment with other experimental drugs
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Evaluate the proportion of patients who are progression-free (defined as progression according to RECIST 1.1 criteria, or death) at 6 months (PFS-6) from registration into the trial.;Secondary Objective: -Overall survival (OS), defined as time between the date of registration and the date of death for any cause or the date they were last known to be alive. <br>-PFS, defined as the time between the date of registration and the date of documented radiological PD according to RECIST 1.1 criteria or death from any cause, whichever occurs first, or the date of last follow-up or last available tumor assessment if no further follow-up for disease progression is performed.<br>-RECIST radiological response rate. <br>-CA19-9 response rate.<br>-Safety;Primary end point(s): Evaluate the proportion of patients who are progression-free at 6 months (PFS-6);Timepoint(s) of evaluation of this end point: 6 months
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Overall survival (OS); The progression free survival (PFS); RECIST radiological response rate.; Ca19.9 response rate.; Safety;Timepoint(s) of evaluation of this end point: 3 years; 3 years; until drug unacceptable toxicity or medical decision.; until drug unacceptable toxicity or medical decision.; until drug unacceptable toxicity or medical decision.