Gemcitabine plus nab-PAclitaxel as switch maiNTEnance versus cONtinuation of modified FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: the PANThEON phase III Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione GONO G.I.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 Mar 2025 → ongoing

Decision date (initial)

2025-01-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Fondazione Rising Tide · Fondazione Gono

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the efficacy of switch maintenance Gem-NabP after a mFOLFIRINOX-based 3-months induction as compared with mFOLFIRINOX continuation, in terms of overall survival (OS)

Secondary objectives 6

1. To estimate the efficacy of switch maintenance with Gem-NabP after a mFOLFIRINOX-based 3-months induction as compared with mFOLFIRINOX continuation, in terms of progression free survival (PFS) and time to treatment failure (TTF)
2. To estimate the activity of switch maintenance with Gem-NabP after a mFOLFIRINOX-based 3-months induction as compared with mFOLFIRINOX continuation, in terms of objective response rate (ORR) and disease control rate (DCR)
3. To estimate the impact of switch maintenance strategy with Gem-NabP compared to mFOLFIRINOX continuation on patients’ quality of life
4. To evaluate the safety profile of switch maintenance with Gem-NabP after a mFOLFIRINOX-based 3-months induction as compared with mFOLFIRINOX continuation
5. To evaluate the proportion of patients starting induction chemotherapy but who are not eligible for randomization due to early disease progression or other causes
6. To estimate the impact of switch maintenance strategy with Gem-NabP compared to mFOLFIRINOX continuation on subsequent treatment lines

Conditions and MedDRA coding

advanced pancreatic cancer

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. Patient able and willing to provide written informed consent and to comply with the study protocol.
2. Subjects must be ≥18 years.
3. Histologically or cytologically confirmed unresectable locally advanced or metastatic pancreatic adenocarcinoma eligible for treatment in the first-line setting.
4. Presence of measurable or non-measurable disease assessed by CT scan and/or MRI according to RECIST 1.1 (Appendix I of the protocol). Note: any lesion which has been subjected to percutaneous therapies or radiotherapy should not be considered measurable, unless the lesion has clearly progressed since the procedure.
5. Availability of archival tumor sample (primary tumor or metastatic site) for biomarker analysis.
6. ECOG performance status of 0-1 (if age < 70 years). If age ≥70 years, ECOG PS must be 0.
7. Estimated life expectancy > 3 months.
8. Adequate baseline hematologic function characterized by the following at screening: a. Absolute Neutrophil Count (ANC) ≥ 1.5 × 109/L b. platelets count ≥ 100 × 109/L c. hemoglobin ≥ 9 g/dl. Note: prior transfusions for patients with low hemoglobin are allowed.
9. Adequate liver function characterized by the following at screening:a. Serum total bilirubin ≤ 1.5 × ULN and < 2 mg/dL. Note: Subjects with Serum total bilirubin ≥ 1.5 × ULN and conjugated bilirubin ≤ ULN or < 40% of total bilirubin are allowed. b. Serum transaminases (AST and/or ALT) < 3 x ULN (< 5 x ULN in presence of liver metastasis). In participants with elevated AST or ALT, the values must be stable for at least 2 week and with no evidence of biliary obstruction by imaging.
10. Adequate renal function, i.e. serum creatinine ≤ 1.5 x institutional ULN and calculated by Cockroft-Gault formula or directly measured creatinine clearance ≥ 50 mL/min.
11. Adequate coagulation functions as defined by International Normalized Ratio (INR) ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy).
12. No presence of complete dihydropyrimidine dehydrogenase (DPYD) enzyme deficiency (homozygous of the following DPYD polymorphisms: c1679GG, c1905+1AA, c2846TT) with DPYD gene testing mandatory at screening as per national guidelines. UDP-glucuronosyltransferase 1A1 (UGT1A1) testing is not mandatory. However, if UGT test is routinely performed in the participating centers, enrolment of patients carriers of variants of DPYD and homozygous variant UGT1A1 [7/7] has to be discussed with the Sponsor. See Appendix VI of the full protocol for details.
13. Women of childbearing potential must agree to remain abstinent (refrain from sexual intercourse) or use highly effective contraceptive methods, as defined in Appendix V of the full protocol, during the treatment period and for at least 7 months after the last administration of study treatments.
14. Negative serum pregnancy test within 7 days of starting study treatment in pre-menopausal women and women <1 year after the onset of menopause.
15. Men must agree to remain abstinent (refrain from sexual intercourse) or use highly effective contraceptive methods, as defined in Appendix V of the full protocol, during the treatment period and for at least 7 months after the last administration of study treatments.
16. Participants must agree not to donate eggs/sperm for future use for the purposes of assisted reproduction during the study and for a period of 7 months after receiving the last dose of study treatment. Female and male participants should consider preservation of eggs/sperm prior to study treatment as anti-cancer treatments may impair fertility.

Exclusion criteria 14

1. Pancreatic neuroendocrine, acinar, squamous/adenosquamous, or islet tumors.
2. Previous or concurrent systemic (eg cytotoxic or targeted or other experimental drugs) therapy for advanced pancreatic adenocarcinoma. Note: previous (neo)adjuvant or perioperative anti-cancer therapy for non-metastatic, resectable or borderline resectable PDAC, associated with surgery on the primary tumor, is allowed if ≥ 9 months have elapsed from the last dose of therapy and documented disease progression or relapse.
3. Major surgery or radiation therapy performed within ≤4 weeks before randomization. Palliative radiotherapy to bone lesions is allowed if performed ≥ 2 weeks prior to start of study treatment. Patients must have recovered from any effect from major surgery.
4. Known allergy or hypersensitivity to study drugs and/or their excipients.
5. Unresolved toxicity ≥ CTCAE grade 2 attributed to any prior therapies (e.g. grade ≥2 peripheral neurotoxicity), excluding anemia or alopecia.
6. Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that requires directed therapy (such as radiotherapy or surgery) or increasing doses of corticosteroids 2 weeks prior to study entry. Participants with treated symptomatic brain metastases should be neurologically stable for 4 weeks post-treatment and prior to study entry.
7. Any known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years prior to study entry except for curatively treated basal cell carcinoma of the skin, in situ carcinoma of the cervix, and prostate cancer.
8. Know active uncontrolled hepatitis B or hepatitis C. Patients with a past or resolved HBV infection are eligible. Patients with chronic disease controlled by antiviral therapy or requiring prophylactic treatment are eligible.
9. Chronic or current active infectious disease requiring systemic antibiotics or antifungal treatment within 2 weeks prior to enrollment.
10. Known uncontrolled HIV infection. HIV-positive patients are eligible if their CD4+ cell count amounts to 300 cells per μL or more; HIV viral load must be undetectable per standard of care assay, and they must be compliant with antiretroviral treatment.
11. Pregnant or breast-feeding patient, or patient planning to become pregnant within 7 months after the end of treatment.
12. Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA > II, unstable angina pectoris, history of myocardial infarction within 3 months before study entry, significant arrhythmia).
13. Presence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent.
14. Any serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival (OS) i.e. the time from randomization to death or last follow-up for alive patients.

Secondary endpoints 6

1. PFS, i.e. the time from randomization to disease progression or death from any cause TTF, i.e. time from randomization to discontinuation of treatment for any reason, including progressive disease, treatment toxicity and death.
2. ORR, i.e. the percentage of patients achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria DCR, i.e. the percentage of patients achieving a complete (CR) or partial (PR) response or a stable disease (SD), according to RECIST 1.1 criteria.
3. Quality of life (QoL), i.e. QoL will be estimated with EORTC QLQ-C30 and the modules PAN26, FA12, CAX24, COMU26 a will be performed with the EORTC QLQ INFO25, which is a valid self-reported instrument consisting of 25 questions. Communication between patients and professionals will be assessed with the EORT QLC COMU26.
4. Toxicity, i.e. the percentage of patients experiencing a specific adverse event, according to National Cancer Institute Common Toxicity Criteria (version 5.0).
5. Proportion of patients not eligible to randomization, i.e. patients who started induction treatment but result not eligible due to i) clinical deterioration or treatment toxicity, ii) withdraw consent or iii) disease progression documented as best response, iv) other causes.
6. Subsequent treatment line frequency, i.e. the percentage of patients who undergo a systemic treatment (excluding locoregional treatments or surgical treatment of unresectable disease) after progression to first line in both arms.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione GONO G.I.

Sponsor organisation

Fondazione GONO G.I.

Address

Via Goffredo Mameli 3/1

City

Genoa

Postcode

16122

Country

Italy

Scientific contact point

Organisation

Gruppo Oncologico Del Nord Ovest

Contact name

Laura Delliponti

Public contact point

Organisation

Gruppo Oncologico Del Nord Ovest

Contact name

Laura Delliponti

Locations

1 EU/EEA country · 28 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 25 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications