Status:
UNKNOWN
Chlorambucil in Metastatic PDAC Patients Bearing a Germ Line DNA Defects Repair Mutations (SALE Trial)
Lead Sponsor:
Michele Reni
Conditions:
Pancreatic Ductal Adenocarcinoma
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
The main objective of this trial is to explore the activity of chlorambucil, an alkylating agent commonly used in chronic lymphocytic leukemia treatment, in metastatic patients, gBRCA, including VUS, ...
Detailed Description
Nowadays, treatment strategies for patients affected by metastatic pancreatic ductal adenocarcinoma (PDAC) are still very scant. Gemcitabine and fluoropyrimidine based chemotherapy regimens are standa...
Eligibility Criteria
Inclusion
- Pathologically confirmed pancreatic adenocarcinoma
- Age ≥ 18 years
- ECOG PS 0-2
- Stage IV disease
- Identified genetic aberrations that are associated with homologous recombination deficiency (HRD)
- Cohort A: Documented mutation in gBRCA1 or gBRCA2 that is predicted to be deleterious or suspected deleterious
- Cohort B: BRCA1 or BRCA2 mutations that are considered to be of uncertain/unknown significance (VUS)
- Cohort C: Patients with other identified genetic aberrations that are associated with HRD
- Adequate PFS during previous platinum-based chemotherapy for at least 4 months before progression
- 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.
- Able to take oral medication
- Progression during or after platinum-based chemotherapy
- Other prior chemotherapy apart from first-line treatment for pancreatic cancer, are allowed, including maintenance treatment with PARP inhibitors
- More than 2 weeks since prior chemotherapy end
- Signed written informed consent
- QTc \<450 msec or QTc \<480 msec for patients with bundle branch block
Exclusion
- 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
- Active and uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
- Vaccination with vaccines called "live", since this treatment causes a drop of immunity defenses and a serious infection could result fatal.
- History of seizure, head trauma and treatment with anti-epileptogenic drugs
- Hypersensitivity to chlorambucil or to any excipients, in particular lactose
- Recent radiotherapy (at least 4 weeks) or previous treatment with other cytotoxic agents
- BRCA-mutated advanced pancreatic cancer who did not undergo maintenance with olaparib after platinum-based chemotherapy
- 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
- Concomitant PARP inhibitors therapy
- Life expectancy less than 3 months, in the opinion of the investigator
- 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
- Symptomatic duodenal stenosis
- CT contrast medium allergy and claustrophobia to RM investigation
- Any significant medical condition laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
- Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
- Any condition that confounds the ability to interpret data from the study
- Any familiar, sociologic or geographic conditions that can potentially interfere with the adhesion to the protocol or to the follow-up
- Pregnant or nursing. Adequate contraception is defined as oral hormonal birth control, intrauterine device, and male partner sterilization (if male partner is sole partner for that subject) and the double barrier method (condom or occlusive cap plus spermicidal agent).
- Concurrent treatment with other experimental drugs
Key Trial Info
Start Date :
December 18 2020
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
December 1 2023
Estimated Enrollment :
20 Patients enrolled
Trial Details
Trial ID
NCT04692740
Start Date
December 18 2020
End Date
December 1 2023
Last Update
September 21 2023
Active Locations (1)
Enter a location and click search to find clinical trials sorted by distance.
1
IRCCS San Raffaele
Milan, Italy, 20132