First-line Therapy in Metastatic PDAC

NCT03487016 | Unknown Phase 2

• 1 other identifier: 2017-003496-54
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 1

Brief Summary

The overarching hypothesis of this trial is that the NAPOLI regimen and alternating cycles of NAPOLI and mFOLFOX6 (seq-NAPOLI-FOLFOX) are superior to the current standard of care gemcitabine/nab-paclitaxel. Furthermore, we propose that the NAPOLI regimen and seq-NAPOLI-FOLFOX display favourable safety profiles and allow for longer first line treatment and higher rate of transition into the second line setting.

Conditions

Metastatic Pancreatic Cancer

Keywords

Pancreatic Cancer; First line; Metastatic

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  PFS

  60 months

Secondary Outcomes (9)

• Overall survival

  60 months

• Objective response rate

  60 months

• Disease control rate

  60 months

• Duration of study treatment

  60 months

• Type, incidence, causal relationship and severity of adverse events according to NCI CTCAE version 4.03

  60 months

Other Outcomes (4)

• Molecular subtypes of pancreatic cancer as predictors of response to chemotherapy

  60 months

• Evaluation of radiologic early tumor shrinkage

  60 months

• Evaluation of radiologic depth of response

  60 months

Study Arms (3)

A: Gemcitabine/nab-Paclitaxel (Standard)

ACTIVE COMPARATOR

Nab-paclitaxel 125 mg/m2, i.v. infusion over about 30 minutes followed by Gemcitabine 1000 mg/m2 as a 30-minute i.v. infusion on D1, D8, D15 of a 28-day cycle. Treatment is given until disease progression or the occurrence of unacceptable toxicity.

Drug: Gemcitabine; Drug: Nab-paclitaxel

B: NAPOLI regimen

EXPERIMENTAL

On Day 1 of a 14-day cycle: Liposomal irinotecan 80 mg/m2 i.v. over about 90 minutes followed by Folinic acid 400 mg/m2 i.v. over about 30 minutes followed by 5-FU 2400 mg/m2 i.v. over about 46 h (pump) Treatment is given until disease progression or the occurrence of unacceptable toxicity.

Drug: 5-FU; Drug: Irinotecan Liposomal Injection

C: seq-NAPOLI-FOLFOX

EXPERIMENTAL

The NAPOLI regimen and the mFOLFOX6 regimen are applied in an alternating fashion, starting with the NAPOLI regimen. NAPOLI: On Day 1 of a 14-day cycle: Liposomal irinotecan 80 mg/m2 i.v. over about 90 minutes followed by Folinic acid 400 mg/m2 i.v. over about 30 minutes followed by 5-FU 2400 mg/m2 i.v. over about 46 h (pump) mFOLFOX6: On Day 1 of a 14-day cycle: Oxaliplatin 85 mg/m2 as i.v. infusion over 2 to 6 hours according to local practice at trial site Folinic acid 400 mg/m2 as i.v. infusion; infusion duration according to local practice at trial site followed by 5-FU 2400 mg/m2 i.v. over about 46 h (pump) Treatment is given until disease progression or the occurrence of unacceptable toxicity.

Drug: 5-FU; Drug: Irinotecan Liposomal Injection; Drug: Oxaliplatin

Interventions

Gemcitabine DRUG

Arm A

Also known as: Gemzar

A: Gemcitabine/nab-Paclitaxel (Standard)

Nab-paclitaxel DRUG

Arm A

Also known as: Abraxane

A: Gemcitabine/nab-Paclitaxel (Standard)

5-FU DRUG

Arm B Arm C

Also known as: 5-Fluoruracil

B: NAPOLI regimen; C: seq-NAPOLI-FOLFOX

Irinotecan Liposomal Injection DRUG

Arm B Arm C

Also known as: Onivyde

B: NAPOLI regimen; C: seq-NAPOLI-FOLFOX

Oxaliplatin DRUG

Arm C

Also known as: Trans-l-diaminocyclohexanoxalatoplatin

C: seq-NAPOLI-FOLFOX

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients ≥ 18 years of age and ≤ 75 years
• Histologically (not cytologically) confirmed diagnosis of metastatic pancreatic ductal adenocarcinoma (PDAC) \[Stage IV according to UICC TNM edition 8 of 201622: each T, each N, M1\]
• No option for surgical resection or radiation in curative intent
• At least one unidimensionally measurable tumor lesion (according to RECIST 1.1)
• ECOG performance status 0 - 1
• Life expectancy at least 3 months
• Adequate hepatic, renal and bone marrow function, defined as:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Haemoglobin ≥ 9 g/dL
• Thrombocytes ≥ 100 x 109/L
• Total bilirubin ≤ 1.5 x ULN. Patients with a biliary stent may be included provided that bilirubin level after stent insertion decreased to ≤ 1.5 x ULN and there is no cholangitis.
• AST/GOT and/or ALT/GPT ≤ 2.5 x ULN or in case of liver metastasis ≤ 5 x ULN)
• Serum creatinine within normal limits or creatinine clearance ≥ 60 mL/min/1.73 m2 as calculated by CKD-EPI formula for patients with serum creatinine levels above or below the institutional normal value.
• Females of childbearing potential (FCBP) must have a negative highly sensitive serum pregnancy test within 7 days of the first administration of study treatment and they must agree to undergo a further pregnancy tests at monthly intervals and at the end of treatment visit and FCBP must either agree to use and be able to take highly effective contraceptive birth control methods (Pearl Index \< 1) during the course of the study and for at least 1 month after last administration of study treatment. Complete sexual abstinence is acceptable as a highly effective contraceptive method only if the subject is refraining from heterosexual intercourse during the entire study treatment and at least one month after the discontinuation of study treatment and the reliability of sexual abstinence is in line with the preferred and usual lifestyle of the subject. A female subject following menarche is considered to be of childbearing potential unless she is naturally amenorrhoeic for ≥ 1 year without an alternative medical reason, or unless she is permanently sterile.
• Males must agree to use condoms during the course of the trial and for at least 6 months after last administration of study drugs or practice complete abstinence from heterosexual intercourse.

You may not qualify if:

• Locally advanced PDAC without metastasis
• Symptomatic/clinically significant ascites (expected indication for repeated paracentesis)
• Known metastatic disease to the brain. Brain imaging is required in symptomatic patients to rule out brain metastases, but is not required in asymptomatic patients.
• Previous palliative chemotherapy or other palliative systemic tumor therapy for metastatic disease of PDAC
• Previous gemcitabine or 5-FU based treatment with exception of gemcitabine/fluoropyrimidine based treatment applied in the neoadjuvant or adjuvant setting (before/after potential curative R0 or R1 resection) and if the neoadjuvant/adjuvant chemotherapy was terminated at least 6 months before randomization
• Previous radiotherapy of PDAC with exception of radiotherapy in the context of a neoadjuvant or adjuvant treatment setting that was terminated at least 6 months before randomization
• Any major surgery within the last 4 weeks before randomization
• Clinically significant decrease in performance status within 2 weeks of intended first administration of study medication (by medical history)
• Severe tumor-related cachexia and/or known weight loss \> 15% within one month before study enrollment
• Pre-existing polyneuropathy ≥ grade 2 according to CTCAE version 4.03
• Gastrointestinal disorders that might interfere with the absorption of the study drug and gastrointestinal disorders with diarrhoea as a major symptom (e.g. Crohn's disease, malabsorption), and chronic diarrhoea of any aetiology CTCAE version 4.03 grade ≥ 2
• Any other severe concomitant disease or disorder, which could influence patient's ability to participate in the study and his/her safety during the study or interfere with interpretation of study results e.g. active infection, uncontrolled hypertension, clinically significant cardiovascular disease e.g. cerebrovascular accident (≤ 6 months before study start), myocardial infarction (≤ 6 months before study start), unstable angina, heart failure ≥ NYHA functional classification system grade 2, severe cardiac arrhythmia requiring medication, metabolic dysfunction, severe renal disorder.
• Any other malignancies than PDAC within the last 5 years before study start, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer
• Hypersensitivity to the study drugs or to any of the excipients or to compounds with similar chemical or biologic composition
• Use of strong CYP3A4 inhibitors (CYP3A4 inhibitors have to be discontinued at least one week prior to start of study treatment).

Sponsors & Collaborators

• Ludwig-Maximilians - University of Munich: lead

Study Sites (1)

Klinikum der Universitaet Muenchen - Campus Grosshadern

Munich, 81377, Germany

Location

MeSH Terms

Conditions

Pancreatic Neoplasms; Neoplasm Metastasis

Interventions

Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Fluorouracil; irinotecan sucrosofate; Oxaliplatin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Uracil; Pyrimidinones; Coordination Complexes

Study Officials

• Volker Heinemann, MD

  LMU Munich

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: March 4, 2018
• First Posted: April 3, 2018
• Study Start: February 15, 2019
• Primary Completion: July 1, 2022
• Study Completion: July 1, 2023
• Last Updated: September 8, 2022

Record last verified: 2022-09

Locations

DE (1)