AzTrials
AzTrials

Pancreatic Ductal AdenocarcinomaPhase 2SALENCT04692740

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

A Phase 2 study testing Chlorambucil, Oral, 2 Mg in people with Pancreatic Ductal Adenocarcinoma, run by Michele Reni at 1 site in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pancreatic Ductal Adenocarcinoma
What is being tested?
Chlorambucil, Oral, 2 Mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteItaly
Study dates
18 Dec 2020to Dec 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 18Show fewer
  • 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

Who cannot join

  • 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
Show all 19Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Italy1 site
  • IRCCS San Raffaele

    Milan, 20132

Other trials in Italy

About this study

Official title: A Pilot Study of Chlorambucil in Pre-treated Metastatic Pancreatic Adenocarcinoma Patients Bearing a Germ Line BRCA or Other DNA Defects Repair (DDR) Mutations.

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.

Read the 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 standard I line chemotherapy. Recently, landmark genome-wide studies revealed the existence of a distinct subpopulation of PDAC with highly unstable genomic properties, due to mutations in DNA Damage Repair genes (DDR), in particular BRCA1/2 mutations. Germline mutations cause a deficiency in deoxyribonucleic acid (DNA) damage repair due to inhibition of DNA double-strand breaks repair by the mechanism of homologous recombination. Cancer cells rely on DNA repair to survive the damage induced by genotoxic stress and DNA repair enables cancer cells to accumulate genomic alterations that contribute to their aggressive phenotype. BRCA1/2 abrogation and homologous repair deficiency (HRD) confer sensitivity to DNA damage-inducing drugs, in particular those inflicting cytotoxic DNA crosslinks that interfere with DNA replication. The sensitivity of BRCA1/2-mutated tumors to platinum compounds has been validated in multiple pre-clinical and clinical studies. Nevertheless, similar lesions are induced by DNA-alkylating agents, which include mono-functional (e.g. mitomycin C) or bifunctional alkylators (e.g. chlorambucil). Small molecule inhibitors of poly(ADP-ribose) polymerase (PARP) have been recently developed and they showed an interesting activity and efficacy in breast, ovarian and pancreatic cancer tumors. Although platinum drugs and PARP inhibitors show initially good responses in the clinic, most patients acquire resistance to these drugs. Chlorambucil shows high selective toxicity against human cells and xenograft tumors with compromised BRCA1/2 function. Patients affected by metastatic ductal adenocarcinoma, pretreated with at least one previous platinum-based chemotherapy, will be treated with oral chlorambucil for 42 consecutive days After restaging, responder patients and those with stable disease will receive for 14 consecutive days every 28 days until disease progression (RECIST 1.1 criteria) or unbearable toxicity, patient refusal or medical decision.

Being tested
Chlorambucil, Oral, 2 Mg
Keywords
chlorambucil, BRCA mutations, DNA defect repair mutations

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Chlorambucil, Oral, 2 MgDrug

    Eligible patients will be treated with Chlorambucil 6 mg/m2 daily p.o. for 42 consecutive days (weeks 1-6). After restaging, responder patients (complete or partial response) and those with stable disease will receive Chlorambucil 6 mg/m2 daily p.o for 14 consecutive days every 28 days until disease progression or unbearable toxicity, patient refusal or medical decision. Patients' clinical data will be collected pseudo-anonymously and a sequential identification code number will be assigned to each patient enrolled in the study.

Study groups in NCT04692740
Study groupRoleWhat they receive
ChlorambucilExperimentalNot described
Receives: Drug: Chlorambucil, Oral, 2 Mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free survival evaluation

    Evaluate the proportion of patients who are progression-free defined as progression according to RECIST 1.1 criteria or death. Progression free survival (PFS) is 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 tumour assessment if no further follow-up for disease progression is performed.

    Measured: 6 months

Secondary outcomes (4)
  1. Overall survival evaluation

    Overall survival (OS) is 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

    Measured: 36 months

  2. Radiological response rate

    Radiological response evaluation by using RECIST 1.1 criteria

    Measured: 6 months

  3. Biochemical response rate

    Biochemical response evaluation by testing Ca19.9 marker

    Measured: 6 months

  4. Drug safety

    Drug toxicity evaluation by using appropriate SAE report form

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jan 2021
  2. Study start18 Dec 2020
  3. Primary completion4 Jan 2023
  4. Study completionDec 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04692740
Sponsor's protocol ID
PACT29
Acronym
SALE
Status last verified
Sep 2023
First submitted
30 Dec 2020
Last updated
21 Sep 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, Miller DK, Christ AN, Bruxner TJ, Quinn MC, Nourse C, Murtaugh LC, Harliwong I, Idrisoglu S, Manning S, Nourbakhsh E, Wani S, Fink L, Holmes O, Chin V, Anderson MJ, Kazakoff S, Leonard C, Newell F, Waddell N, Wood S, Xu Q, Wilson PJ, Cloonan N, Kassahn KS, Taylor D, Quek K, Robertson A, Pantano L, Mincarelli L, Sanchez LN, Evers L, Wu J, Pinese M, Cowley MJ, Jones MD, Colvin EK, Nagrial AM, Humphrey ES, Chantrill LA, Mawson A, Humphris J, Chou A, Pajic M, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Lovell JA, Merrett ND, Toon CW, Epari K, Nguyen NQ, Barbour A, Zeps N, Moran-Jones K, Jamieson NB, Graham JS, Duthie F, Oien K, Hair J, Grutzmann R, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Rusev B, Capelli P, Salvia R, Tortora G, Mukhopadhyay D, Petersen GM; Australian Pancreatic Cancer Genome Initiative; Munzy DM, Fisher WE, Karim SA, Eshleman JR, Hruban RH, Pilarsky C, Morton JP, Sansom OJ, Scarpa A, Musgrove EA, Bailey UM, Hofmann O, Sutherland RL, Wheeler DA, Gill AJ, Gibbs RA, Pearson JV, Waddell N, Biankin AV, Grimmond SM. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016 Mar 3;531(7592):47-52. doi: 10.1038/nature16965. Epub 2016 Feb 24.

    PubMed 26909576
  • Pihlak R, Valle JW, McNamara MG. Germline mutations in pancreatic cancer and potential new therapeutic options. Oncotarget. 2017 Apr 20;8(42):73240-73257. doi: 10.18632/oncotarget.17291. eCollection 2017 Sep 22.

    PubMed 29069866
  • Rebelatto TF, Falavigna M, Pozzari M, Spada F, Cella CA, Laffi A, Pellicori S, Fazio N. Should platinum-based chemotherapy be preferred for germline BReast CAncer genes (BRCA) 1 and 2-mutated pancreatic ductal adenocarcinoma (PDAC) patients? A systematic review and meta-analysis. Cancer Treat Rev. 2019 Nov;80:101895. doi: 10.1016/j.ctrv.2019.101895. Epub 2019 Sep 6.

    PubMed 31542591
  • Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algul H, O'Reilly EM, McGuinness D, Cui KY, Schlienger K, Locker GY, Kindler HL. Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. N Engl J Med. 2019 Jul 25;381(4):317-327. doi: 10.1056/NEJMoa1903387. Epub 2019 Jun 2.

    PubMed 31157963
  • Tacconi EM, Badie S, De Gregoriis G, Reislander T, Lai X, Porru M, Folio C, Moore J, Kopp A, Baguna Torres J, Sneddon D, Green M, Dedic S, Lee JW, Batra AS, Rueda OM, Bruna A, Leonetti C, Caldas C, Cornelissen B, Brino L, Ryan A, Biroccio A, Tarsounas M. Chlorambucil targets BRCA1/2-deficient tumours and counteracts PARP inhibitor resistance. EMBO Mol Med. 2019 Jul;11(7):e9982. doi: 10.15252/emmm.201809982. Epub 2019 May 24.

    PubMed 31273933

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Chlorambucil, Oral, 2 Mg in people with Pancreatic Ductal Adenocarcinoma, run by Michele Reni at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 21 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival evaluation (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04692740, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2023.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in