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Metastatic Pancreatic CancerPhase 2FOOTPATHNCT03487016

First-line Therapy in Metastatic PDAC

A Phase 2 study testing Gemcitabine, Nab-paclitaxel and 5-FU in people with Metastatic Pancreatic Cancer, run by Ludwig-Maximilians - University of Munich at 1 site in Germany.

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 The sponsor has not verified this record for over two years, so it may be out of date.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
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Metastatic Pancreatic Cancer
What is being tested?
Gemcitabine, Nab-paclitaxel and 5-FU
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
270 participants
Where
1 siteGermany
Study dates
15 Feb 2019to Jul 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 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.
  • Signed and dated informed consent before the start of any specific protocol procedures
  • Patient's legal capacity to consent to study participation

Who cannot join

  • 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
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  • 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).
  • Use or strong UGT1A1 inhibitors or strong CYP3A4 inducers unless there are no therapeutic alternatives.
  • Known glucuronidation deficiency (Gilbert's syndrome) (specific screening not required)
  • Known DPD deficiency (specific screening not required)
  • Requirement for concomitant antiviral treatment with sorivudine or brivudine
  • Continuing abuse of alcohol, drugs, or medical drugs
  • Pregnant or breast-feeding females or FCBPs unable to either perform highly effective contraceptive measures or practice complete abstinence from heterosexual intercourse
  • Current or recent (within 4 weeks prior to randomization) treatment with an investigational drug or participation in an investigational clinical trial

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Klinikum der Universitaet Muenchen - Campus Grosshadern

    Munich, 81377

Other trials in Germany

About this study

Official title: A Multicenter Randomized Phase II Study to Determine the Optimal First-line Chemotherapy Regimen in Patients With Metastatic Pancreatic Cancer

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.

Read the detailed description

Pancreatic ductal adenocarcinoma (PDAC) remains an almost uniformly lethal disease. Although there has been significant progress in understanding of the underlying molecular biology of pancreatic cancer, this progress has not translated into substantially better outcome.

Alarmingly, the number of pancreatic cancer cases is constantly rising and pancreatic cancer will be the second most frequent cause of cancer related death by 2030.

Accordingly, novel therapeutic strategies for patients with pancreatic cancer are desperately needed.

Recently, the combination of gemcitabine and nab-paclitaxel proofed to be superior when compared to single agent gemcitabine (overall survival [OS] 8.7 months in the nab-paclitaxel/gemcitabine group versus 6.6 months in the gemcitabine group; hazard ratio for death, 0.72; 95% confidence interval [CI], 0.62 to 0.83; P<0.001). Consequently, this combination therapy is now regarded as a standard treatment option for patients with metastatic pancreatic cancer and should therefore serve as control for future clinical studies.

Furthermore, the combination of 5-fluorouracil (5-FU), irinotecan and oxaliplatin (FOLFIRINOX) was found to be more effective in the treatment of metastatic pancreatic cancer when compared to gemcitabine monotherapy (overall survival 11.1 month in the FOLFIRINOX group versus 6.8 months in the gemcitabine group - hazard ratio for death, 0.57; 95% confidence interval [CI], 0.45 to 0.73; P<0.001). However, this increased activity came at the cost of higher treatment-related side effects.

Recently, the NAPOLI-1 trial yielded promising results for the combination of liposomal irinotecan (nal-Iri) in combination with 5-FU/folinic acid (FA) in patients pretreated with a gemcitabine-based first-line regimen.

Finally, Phase II data show promising efficacy and favorable toxicity with conventional FOLFIRI.3 in the treatment of advanced pancreatic cancer.

Furthermore, studies in colorectal cancer demonstrated a comparable efficacy and favorable toxicity when comparing conventional FOLFOXIRI (+ bevacizumab) and sequential FOLFOXIRI (alternating FOLFOX and FOLFIRI) in combination with bevacizumab.

With these novel treatment options at hand it is imperative to define the optimal first-line treatment modality in order to allow for an optimized treatment sequence to ensure for maximal success with acceptable toxicity.

Being tested
Gemcitabine, Nab-paclitaxel, 5-FU, Irinotecan Liposomal Injection, Oxaliplatin
Keywords
Pancreatic Cancer, First line, Metastatic
Medical subject headings
Pancreatic Neoplasms, Neoplasm Metastasis

What participants receive

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

  • GemcitabineDrug

    Also called Gemzar

    Arm A

  • Nab-paclitaxelDrug

    Also called Abraxane

    Arm A

  • 5-FUDrug

    Also called 5-Fluoruracil

    Arm B Arm C

  • Irinotecan Liposomal InjectionDrug

    Also called Onivyde

    Arm B Arm C

  • OxaliplatinDrug

    Also called Trans-l-diaminocyclohexanoxalatoplatin

    Arm C

Study groups in NCT03487016
Study groupRoleWhat they receive
A: Gemcitabine/nab-Paclitaxel (Standard)Active comparatorNab-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.
Receives: Drug: Gemcitabine; Drug: Nab-paclitaxel
B: NAPOLI regimenExperimentalOn 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.
Receives: Drug: 5-FU; Drug: Irinotecan Liposomal Injection
C: seq-NAPOLI-FOLFOXExperimentalThe 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.
Receives: Drug: 5-FU; Drug: Irinotecan Liposomal Injection; Drug: Oxaliplatin

What is being measured

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

  1. Progression-free survival

    PFS

    Measured: 60 months

Secondary outcomes (9)

  1. Overall survival

    OS

    Measured: 60 months

  2. Objective response rate

    ORR

    Measured: 60 months

  3. Disease control rate

    DCR

    Measured: 60 months

  4. Duration of study treatment

    Time on therapy

    Measured: 60 months

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

    Safety

    Measured: 60 months

  6. Efficacy of second-line chemotherapy

    Second Line Therapy I

    Assessed through progression free survival after initiation of second-line therapy.

    Measured: 60 months

  7. Choice of second-line chemotherapy

    Second Line Therapy II

    Type of second line therapy will be recorded in a descriptive manner based on available health records.

    Measured: 60 months

  8. Duration of second-line chemotherapy

    Second Line Therapy III

    Measured: 60 months

  9. Quality of life as assessed by EORTC-QLQ-C30

    Quality of life will be assessed by the European Organisation for Research and Treatment of Cancer (EORTC) core Quality of Life Questionnaire (QLQ).

    The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale.

    All of the scales ands ingle-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

    Scoring is done based on the following document: EORTC QLQ-C30 Scoring Manual

    Measured: 60 months

Timeline

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

  1. First posted3 Apr 2018
  2. Study start15 Feb 2019
  3. Primary completion1 Jul 2022
  4. Study completionJul 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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
270 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03487016
Sponsor's protocol ID
2017-003496-54
Other IDs
2017
Acronym
FOOTPATH
Status last verified
Sep 2022
First submitted
4 Mar 2018
Last updated
8 Sep 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Gemcitabine, Nab-paclitaxel and 5-FU in people with Metastatic Pancreatic Cancer, run by Ludwig-Maximilians - University of Munich at 1 site in Germany.

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 17 inclusion and 22 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 8 Sep 2022. 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 Germany. 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 (time frame: 60 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 NCT03487016.

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 8 Sep 2022.

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