Trial Title:
Olaparib in PALB2 Advanced Pancreatic Cancer
NCT ID:
NCT06078787
Condition:
Advanced Pancreatic Cancer
Metastatic Pancreatic Cancer
Conditions: Official terms:
Pancreatic Neoplasms
Olaparib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Olaparib 150 MG
Description:
Olaparib should be dosed 2 x 150 mg tablets (300 BID)
Arm group label:
Olaparb
Summary:
This is a Phase II, non-randomized, multicenter, unblinded open-label study of Olaparib
in monotherapy in participants with advanced (locally advanced/metastatic) PALB2-related
pancreatic cancer that have progressed after at least one treatment for advanced disease.
Detailed description:
This is a Phase II, non-randomized, multicenter, unblinded open-label study of Olaparib
in monotherapy in participants with advanced (locally advanced/metastatic) PALB2-related
pancreatic cancer that have progressed after at least one treatment for advanced disease.
After screening, 16 eligible participants with germline or somatic PALB2 mutations will
be enrolled in this study. All participants will receive Olaparib 300 mg twice a daily
(BID).
Study intervention will continue until documented PD, unacceptable AEs, intercurrent
illness that prevents further administration of the study intervention, investigator's
decision to discontinue the participant, participant withdrawal of consent, pregnancy of
the participant, administrative reasons requiring cessation of study intervention.
After documented PD, each participant will be contacted by telephone every 12 weeks (+-14
days) to assess for survival status until withdrawal of consent to participate in the
study, becoming lost to follow up, death or end of the study, whichever occurs first.
During treatment, efficacy will be evaluated using ORR, PFS, DOC and DCR using RECIST 1.1
Efficacy will also be evaluated by assessing OS. Participants will be evaluated with
radiographic imaging to assess response to intervention at regular intervals throughout
the study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Has a histologically or cytologically confirmed pancreatic adenocarcinoma
- Has advanced (unresectable or metastatic) pancreatic cancer by American Joint
Committee on Cancer 8th Edition
- Has documented mutation in PALB2 gene (germline or somatic) that is predicted to be
deleterious or suspected deleterious.
- Has at least one lesion (measurable) that can be accurately assessed at baseline by
CT scan (or MRI, if the subject is allergic to CT contrast media) and is suitable
for repeated assessment according to RECIST Version 1.1 criteria.
- Has a life expectancy ≥16 weeks.
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or
1, as assessed within 3 days of the treatment initiation.
- Has received at least one systemic treatment for advanced disease (locally advanced
or metastatic disease).
- Has adequate organ function as defined in Table 2; all screening laboratory tests
should be performed within 10 days prior to initiation of study intervention.
- Is male or female, who is at least 18 years of age at the time of signing the
informed consent.
Male Participants Contraceptive use by men should be consistent with local regulations
regarding the methods of contraception for those participating in clinical studies.
- A male participant must agree to use contraception ad detailed in Appendix D of this
protocol during the treatment period and for at least 3 months following the last
dose of Olaparib when having sexual intercourse with pregnant woman or with a WOPBP.
Female partners of male patients should also use a highly effective form of
contraception ([see appendix D for acceptable methods]) if they are of childbearing
potential Male patients should not donate sperm throughout the period of taking
olaparib and for 3 months following the last dose of olaparib.
Female Participants Contraceptive use by women should be consistent with local
regulations regarding the methods of contraception for those participating in clinical
studies.
-
11. A female participant is eligible to participate if she is not pregnant*
(Appendix D), not breastfeeding and at least 1 of the following conditions
applies:
1. Not a WOCBP as defined in Appendix D
OR
2. A WOCBP who agrees to follow the contraceptive guidance in Appendix D during
treatment period and for least one month after the last dose of study
intervention.
Postmenopausal is defined as:
- Amenorrhoeic for 1 year or more following cessation of exogenous hormonal treatments
- Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post
menopausal range for women under 50
- radiation-induced oophorectomy with last menses >1 year ago
- chemotherapy-induced menopause with >1 year interval since last menses
- surgical sterilisation (bilateral oophorectomy or hysterectomy)
- evidence of non-childbearing status for women of childbearing potential is
defined with negative urine or serum pregnancy test within 28 days of study
treatment and confirmed prior to treatment on day 1 (within 24 hours) and
before every cycles.
Informed Consent
- Has (or legally acceptable representative if applicable) provided written informed
consent for the study. The participant may also provide consent/assent for future
biomedical research. However, the participant may participate in the main trial
without participating in the FBR.
Exclusion Criteria:
- Has a known additional malignancy that is progressing or requires active treatment.
Other malignancy unless curatively treated with no evidence of disease for ≥5 years
except: adequately treated non-melanoma skin cancer, curatively treated in situ
cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial
carcinoma.
- Has myelodysplastic syndrome/acute myeloid leukaemia or features suggestive of
MDS/AML.
-
3. Patients with symptomatic uncontrolled brain metastases and/or carcinomatous
meningitis. Subject with previously treated brain metastasis may participate
proved they are stable (without evidence of progression by imaging for at leat
four weeks prior to the first dose of trial treatment and any neurological
symptoms have returned to baseline), no evidence of new or enlarging brain
metastases. The patient can receive a stable dose of corticosteroids before and
during the study as long as these were started at least 4 weeks prior to
treatment. Patients with spinal cord compression unless considered to have
received definitive treatment for this and evidence of clinically stable
disease for 28 days.
-
4. Has a documented weigh loss > 10% from baseline during screening and/or decline
in ECOG PS to >1 between visit and within 73 hours prior to first dose of
therapy.
- Has an active infection requiring systemic therapy.
- Has a known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
- Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade
2) caused by previous cancer therapy, excluding alopecia. Patients previously
treated with Oxaliplatinum who experienced a ≤ G2 neuropathy can be included after
consultation with the study physician
- Patients considered at poor medical risk due to a serious, uncontrolled medical
disorder, non-malignant systemic disease or active, uncontrolled infection. Examples
include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within
3 months) myocardial infarction, uncontrolled major seizure disorder, unstable
spinal cord compression, superior vena cava syndrome, extensive interstitial
bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any
psychiatric disorder that prohibits obtaining informed consent.
- Is unable to swallow orally administered medication or patients with
gastrointestinal disorders likely to interfere with absorption of the study
medication.
- Is a immunocompromised patients, e.g., patients who are known to be serologically
positive for human immunodeficiency virus (HIV).
- Has a known active hepatitis (i.e. Hepatitis B or C).
- Active hepatitis B virus (HBV) is defined by a known positive HBV surface
antigen (HBsAg) result. Patients with a past or resolved HBV infection (defined
as the presence of hepatitis B core antibody and absence of HBsAg) are
eligible.
- Patients positive for hepatitis C virus (HCV) antibody are eligible only if
polymerase chain reaction is negative for HCV RNA.
Prior/concomitant therapy
- Any previous treatment with PARP inhibitor, including Olaparib.
- Has prior systemic chemotherapy, targeted small molecule therapy or radiotherapy
(except for palliative reasons) within 3 weeks prior to study treatment.
- Has received prior therapy with an anti-monoclonal antibody within 4 weeks or who
has not recovered (i.e. <= G1 or at baseline) from adverse events due to agents
administered more than 4 weeks earlier.
-
15. Bone as only site of metastatic disease from pancreatic cancer (bone only
disease)
-
16. Major surgery within 2 weeks of starting study treatment and patients must have
recovered from any effects of any major surgery.
-
17. Is currently receiving known strong CYP3A inhibitors (eg. itraconazole,
telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or
cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or
moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem,
fluconazole, verapamil). The required washout period prior to starting olaparib
is 2 weeks.
-
18. Is currently receiving known strong (eg. phenobarbital, enzalutamide,
phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St
John's Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil).
The required washout period prior to starting olaparib is 5 weeks for
enzalutamide or phenobarbital and 3 weeks for other agents.
-
19. Has received previous allogenic bone marrow transplant or double umbilical cord
blood transplantation (dUCBT).
-
20. Has received a whole blood transfusions in the last 120 days prior to entry to
the study. Packed red blood cells and platelet transfusions are acceptable, if
not performed within 28 days of the first dose of study intervention.
Prior/concurrent clinical study experience
-
21. Patients that is currently participating or has participated in another
clinical study with an investigational product administered in the last 4 weeks
-
22. Patients with a known hypersensitivity to olaparib or any of the excipients of
the product.
Diagnostic assessments
-
23. Has resting ECG indicating uncontrolled, potentially reversible cardiac
conditions, as judged by the investigator (eg., unstable ischemia, uncontrolled
symptomatic arrhythmia, congestive heart failure, QTcF prolongation >500 ms,
electrolyte disturbances, etc.), or patients with congenital long QT syndrome.
-
24. Has a history or current evidence of any condition, therapy or laboratory
abnormality that might confound the results of the trial, interfere with the
subject's participation for the full duration of the trial, or is not in the
best interest of the subject to participate, in the opinion of the treating
investigator.
Other exclusions
- Has a benign variant of PALB2 gene or variant of uncertain (or unknown) significance
(VUS)
- Has a histology other than pancreatic adenocarcinoma (for example, neuroendocrine,
adenosquamous etc.)
- Involvement in the planning and/or conduct of the study
- Judgment by the investigator that the patient should not participate in the study if
the patient is unlikely to comply with study procedures, restrictions and
requirements.
- Is pregnant or breastfeeding,or expecting to conceive or father children within the
projected duration of the trial, starting with the pre-screening or screening visit
through 30-90 days after the last dose of trial treatment.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Aou Modena
Address:
City:
Modena
Zip:
41125
Country:
Italy
Status:
Recruiting
Contact:
Last name:
LAURA CORTESI, MD
Start date:
August 1, 2023
Completion date:
August 1, 2026
Lead sponsor:
Agency:
Azienda Ospedaliero-Universitaria di Modena
Agency class:
Other
Source:
Azienda Ospedaliero-Universitaria di Modena
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06078787
