Chlorambucil in Metastatic PDAC Patients Bearing a Germ Line DNA Defects Repair Mutations (SALE Trial)

• Status: Recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

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, or DDR mutated, previously treated with a platinum-containing chemotherapy.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Michele Reni
• Treatments: Chlorambucil

Criteria

Inclusion Criteria:

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)

1. Cohort A: Documented mutation in gBRCA1 or gBRCA2 that is predicted to be deleterious or suspected deleterious

2. Cohort B: BRCA1 or BRCA2 mutations that are considered to be of uncertain/unknown significance (VUS)

3. 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

Exclusion Criteria:

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. Recent radiotherapy (at least 4 weeks) or previous treatment with other cytotoxic agents

7. BRCA-mutated advanced pancreatic cancer who did not undergo maintenance with olaparib after platinum-based chemotherapy

8. 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

9. Concomitant PARP inhibitors therapy

10. Life expectancy less than 3 months, in the opinion of the investigator

11. 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

12. Symptomatic duodenal stenosis

13. CT contrast medium allergy and claustrophobia to RM investigation

14. Any significant medical condition laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study

15. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study

16. Any condition that confounds the ability to interpret data from the study

17. Any familiar, sociologic or geographic conditions that can potentially interfere with the adhesion to the protocol or to the follow-up

18. 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).

19. Concurrent treatment with other experimental drugs