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Pancreatic CancerPhase 1NCT03883919

Liposomal Irinotecan Plus 5-FU / LV Combined With Paricalcitol in Patients With Advanced Pancreatic Cancer Progressed on Gemcitabine-based Therapy

A Phase 1 study testing 5-FU, Leucovorin and Liposomal Irinotecan in people with Pancreatic Cancer and Pancreas Cancer, run by Washington University School of Medicine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Given the efficacy of nanoliposomal irinotecan as a second-line regimen in pancreatic ductal adenocarcinoma (PDAC), together with the favorable toxicity profile of paricalcitol and its interplay with irinotecan metabolism, the investigators propose a second-line pilot study in advanced PDAC that will enroll patients… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
5-FU, Leucovorin and Liposomal Irinotecan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
11 Jul 2019to 2 Jul 2022
Phase
Phase 1
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

  • Histologically or cytologically confirmed pancreatic adenocarcinoma.
  • Must have progressed on or become intolerant to gemcitabine-containing therapy in the advanced setting (not resectable). This is intended to be a second-line trial.
  • Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
  • At least 18 years of age.
  • Life expectancy > 3 months.
  • ECOG performance status ≤ 1
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  • Normal bone marrow and organ function as defined below:
  • Absolute neutrophil count ≥ 1,500/mcL
  • Platelets ≥ 100,000/mcL
  • Hemoglobin ≥ 9 g/dL
  • Total bilirubin ≤ 1.5 x ULN
  • Serum albumin > 3g/dL
  • AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN unless there are liver metastases, in which case AST and ALT ≤ 5.0 x IULN
  • Creatinine ≤ 1.5 x IULN OR GFR > 50 mL/min
  • Corrected calcium < 10.3 mg/dL
  • Phosphorus ≤ 4.5 mg/dL
  • Patients will require a 2-week washout period from previous gemcitabine-based systemic therapy, a 2-week washout period from previous radiation therapy, and a 4-week washout period from major surgery prior to the first planned dose of study treatment.
  • Prior clinically significant treatment-related toxicity must recover to grade 1 or less prior to the first planned dose of study treatment.
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Who cannot join

  • More than one prior systemic treatment in the advanced setting. Disease recurrence within 6 months of adjuvant therapy is considered one line of systemic treatment.
  • Patients with active renal, ureteral, or bladder stones on the screening imaging.
  • Current use of or anticipated need for alternative, holistic, naturopathic, or botanical formulations used for the purpose of cancer treatment.
  • A history of other malignancy within 2 years previous, with the exception of those basal cell or squamous cell carcinoma of the skin which were treated with local resection only, or carcinoma in situ of the cervix.
  • Currently receiving any other investigational agents.
  • Patients who received FOLFIRINOX or FOLFIRI in the neoadjuvant or adjuvant setting who experienced disease recurrence within 6 months will be excluded (patients who received 5-FU or capecitabine as a radiosensitizer are permitted to enroll.)
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  • Patients with known active/ progressive brain metastases or leptomeningeal involvement will be excluded due to their poor prognosis. Patients with treated/stable brain metastases, defined as patients who have received prior therapy for their brain metastases and whose CNS disease is radiographically stable at study entry, are eligible.
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to paricalcitol, liposomal irinotecan, 5-FU, LV, or other agents used in the study.
  • Clinically significant ascites that requires therapeutic paracentesis or significant pleural effusion that requires therapeutic thoracentesis.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry.
  • Known HIV-positivity not on anti-retroviral therapy, or with CD4+ T cell count < 200/ul (patients with known HIV currently on anti-retroviral therapy with CD4+ T cell count > 200/ul will be included).

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Pilot Study of Liposomal Irinotecan Plus 5-FU / LV Combined With Paricalcitol in Patients With Advanced Pancreatic Cancer Progressed on Gemcitabine-based Therapy

Given the efficacy of nanoliposomal irinotecan as a second-line regimen in pancreatic ductal adenocarcinoma (PDAC), together with the favorable toxicity profile of paricalcitol and its interplay with irinotecan metabolism, the investigators propose a second-line pilot study in advanced PDAC that will enroll patients who have progressed on a gemcitabine-based regimen.

Being tested
5-FU, Leucovorin, Liposomal Irinotecan, Paricalcitol, Serum and plasma blood samples
Medical subject headings
Pancreatic Neoplasms

What participants receive

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

  • 5-FUDrug

    Also called Fluorouracil, Adrucil

    -Standard of care drug

  • LeucovorinDrug

    Also called Wellcovorin, Folinic acid

    -Standard of care drug

  • Liposomal IrinotecanDrug

    Also called nal-IRI, Onivyde

    -Standard of care drug

  • ParicalcitolDrug

    Also called Zemplar, Vitamin D

    -Investigational drug

  • Serum and plasma blood samplesProcedure or surgery

    -baseline, day 1 of each cycle beginning with cycle 2

  • Tumor biopsyProcedure or surgery

    • 5 patients in each arm will be required to undergo a mandatory tumor biopsy from the primary pancreatic site or metastatic site, if safe and feasible, prior to cycle 1
    • After Cycle 3 of treatment, all patients who had a baseline biopsy will be required to undergo a mandatory biopsy of the same site if safe and feasible.
Study groups in NCT03883919
Study groupRoleWhat they receive
Group 1: Paricalcitol 75 mcg Days 1 and 8Experimental* 5-FU, LV, and nal-IRI will be administered at standard fixed doses. Briefly, 5-FU will be given at a dose of 2400 mg/m^2 continuous IV infusion over 46 hours, LV will be given at 400 mg/m^2 IV over 30 minutes, and liposomal irinotecan will be given at a dose of 70 mg/m^2 IV over 90 minutes (unless homozygous for the UGT1A1*28 7/7 allele, in which case the dose will start at 50 mg/m^2 and escalate to 70 mg/m^2 in subsequent cycles if no excessive toxicity is experienced) on Day 1 of each 14-day cycle. * Paricalcitol 75 mcg on Days 1 and 8 * Treatment with liposomal irinotecan plus 5FU/ LV may continue indefinitely, and treatment with paricalcitol may continue for up to 10 cycles (20 weeks)
Receives: Drug: 5-FU; Drug: Leucovorin; Drug: Liposomal Irinotecan; Drug: Paricalcitol; Procedure: Serum and plasma blood samples; Procedure: Tumor biopsy
Group 2: Paricalcitol 7 mcg/kg Days 1 and 8Experimental* 5-FU, LV, and nal-IRI will be administered at standard fixed doses. Briefly, 5-FU will be given at a dose of 2400 mg/m^2 continuous IV infusion over 46 hours, LV will be given at 400 mg/m^2 IV over 30 minutes, and liposomal irinotecan will be given at a dose of 70 mg/m^2 IV over 90 minutes (unless homozygous for the UGT1A1*28 7/7 allele, in which case the dose will start at 50 mg/m^2 and escalate to 70 mg/m^2 in subsequent cycles if no excessive toxicity is experienced) on Day 1 of each 14-day cycle. * Paricalcitol 7 mcg/kg on Days 1 and 8 * Treatment with liposomal irinotecan plus 5FU/ LV may continue indefinitely, and treatment with paricalcitol may continue for up to 10 cycles (20 weeks)
Receives: Drug: 5-FU; Drug: Leucovorin; Drug: Liposomal Irinotecan; Drug: Paricalcitol; Procedure: Serum and plasma blood samples; Procedure: Tumor biopsy

What is being measured

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

  1. Tolerability between two different dose levels of paricalcitol added to the combo regimen of liposomal irinotecan plus 5-FU / LV as measured by the occurrence of grade 3 and 4 toxicities

    -Toxicity will be graded using CTCAE version 5.0

    Measured: Through 30 days after completion of paricalcitol treatment (estimated to be 28 weeks)

Secondary outcomes (7)

  1. Overall response rate (ORR)

    • The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
    • Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm and disappearance of all non-target lesions and normalization of tumor marker level.
    • Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: Through completion of treatment (estimated to be 20 weeks)

  2. Progression-free survival (PFS)

    • PFS: PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
    • Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

    Measured: Through completion of follow-up (estimated to be 72 weeks)

  3. Overall survival (OS)

    -Overall survival (OS) is defined as the date from treatment to death or last follow-up.

    Measured: Through completion of follow-up (estimated to be 72 weeks)

  4. CA19-9 biochemical response rate

    -The biochemical response (BR) is defined as more than 50% of decrease from baseline CA 19-9.

    Measured: Through beginning of cycle 10 (estimated to be 18 weeks)

  5. Duration of overall response

    • The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

    Measured: Through completion of treatment (estimated to be 20 weeks)

  6. Duration of complete response

    • The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented.
    • Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm and disappearance of all non-target lesions and normalization of tumor marker level.

    Measured: Through completion of treatment (estimated to be 20 weeks)

  7. Duration of stable disease

    • Duration of stable disease is measured from the start of the treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started, including the baseline measurements.
    • Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

    Measured: Through completion of treatment (estimated to be 20 weeks)

Timeline

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

  1. First posted21 Mar 2019
  2. Study start11 Jul 2019
  3. Primary completion23 Mar 2021
  4. Study completion2 Jul 2022

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03883919
Sponsor's protocol ID
201905201
Status last verified
Oct 2022
First submitted
18 Mar 2019
Last updated
5 Oct 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Plan for sharing IPD to be determined.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 5-FU, Leucovorin and Liposomal Irinotecan in people with Pancreatic Cancer and Pancreas Cancer, run by Washington University School of Medicine at 1 site in United States.

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 20 inclusion and 12 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: finished, as of the sponsor's last update on 5 Oct 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 United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Tolerability between two different dose levels of paricalcitol added to the combo regimen of liposomal irinotecan plus 5-FU / LV as measured by the occurrence of grade 3 and 4 toxicities (time frame: Through 30 days after completion of paricalcitol treatment (estimated to be 28 weeks)). 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 NCT03883919.

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 5 Oct 2022.

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