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Pancreatic CancerPhase 2NCT05546411

A Trial of NIS793 With FOLFIRINOX in Pancreatic Cancer

A Phase 2 study testing mFOLFIRINOX, 5-Fluorouracil (5-FU) and Oxaliplatin in people with Pancreatic Cancer and Resectable Pancreatic Cancer, run by Kimberly Perez, MD at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study is being done to evaluate the safety and efficacy of adding NIS793 to standard of care FOLFIRINOX treatment for pancreatic cancer. The names of the study interventions involved in this study are: NIS793 FOLFIRINOX (Folinic acid/Leucovorin, 5-Fluorouracil, Irinotecan, and Oxaliplatin) Other interventions may… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
mFOLFIRINOX, 5-Fluorouracil (5-FU) and Oxaliplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
2 sitesUnited States
Study dates
6 Jan 2023to 13 Oct 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • The clinical, radiographic, and pathologic evidence support a diagnosis of pancreatic adenocarcinoma, with histology confirmatory for adenocarcinoma.
  • Subjects must be determined to meet the criteria for resectable or borderline resectable pancreatic cancer based on the M.D. Anderson Cancer Center (MDACC) and Alliance Intergroup Criteria classification at initial diagnosis (Table 1). Patients with locally advanced or metastatic disease are not eligible for this trial.
  • Criteria for resectability of pancreatic cancer
  • Vessel: SMA, Resectable: No extension; normal fat plane between the tumor and the artery, Borderline resectable: Interface between tumor and vessel measuring less than 180º of the circumference of the vessel wall, Locally advanced (Not Eligible): Encased (>180°)
  • Vessel: Celiac axis, Resectable: No extension, Borderline resectable: Interface between tumor and vessel measuring less than 180º of the circumference of the vessel wall, Locally advanced (Not Eligible): Encased and no technical option for reconstruction usually because of extension to the celiac axis/ splenic/left gastric junction or the celiac origin
  • Vessel: Common hepatic artery, Resectable: No extension, Borderline resectable: Reconstructable§, short-segment interface between tumor and vessel of any degree, Locally advanced (Not Eligible): Encased and no technical option for reconstruction usually because of extension to the celiac axis/ splenic/left gastric junction or the celiac origin Vessel: SMV/PV, Resectable: Patent, Borderline resectable:SMV/PV Patent Interface between tumor and vessel measuring 180º or greater of the circumference of the vessel wall, and/or reconstructable§ occlusion Occluded and no technical option for reconstruction, Locally advanced (Not Eligible): Occluded and no technical option for reconstruction
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  • Referenced from: Varadhachary et al., 2006(6) and Katz et al, 2013 (8). SMA, superior mesenteric artery; SMV/PV, superior mesenteric vein/portal vein.
  • Normal vein or artery proximal and distal to the site of suggested tumor-vessel involvement suitable for vascular reconstruction
  • In subjects requiring biliary decompression, biliary stent or drainage using percutaneous transhepatic cholangiogram (PTC) are allowed.
  • Participants must be ≥18 years of age at the time of enrollment.
  • Participants must have an ECOG performance status 0-1 (see Appendix A).
  • Participants must have adequate organ and marrow function as defined as:
  • Absolute neutrophil count ≥1,500/mcL
  • Platelets ≥100,000/mcL
  • Total bilirubin ≤1.5 × institutional upper limit of normal
  • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
  • Creatinine ≤1.5 × institutional upper limit of normal OR
  • Creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above 1.5 × upper limit of normal. Creatinine clearance can be calculated per institutional standard.
  • Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 9 months after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study therapy.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Has locally advanced or metastatic disease as determined by CT scan or MRI.
  • Tumors with histologic features in addition to an adenocarcinoma component are excluded. Variant histologies include but are not limited to adenosquamous, squamous, neuroendocrine, undifferentiated with osteoclast like giant cells, acinar, hepatoid, medullary carcinomas.
  • Has either had any prior chemotherapy or targeted small molecule therapy, or immunotherapy or radiation therapy for pancreatic cancer.
  • Note: If subject received major surgery for reason other than pancreatic cancer they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Has a known prior or current synchronous malignancy, except:
  • Malignancy that was treated with curative intent and for which there has been no known active disease for >5 years prior to enrollment
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  • Curatively treated non-melanoma skin cancer, cervical cancer in situ or prostatic intraepithelial neoplasia, without evidence of prostate cancer.
  • Significant history of uncontrolled cardiac disease defined as uncontrolled hypertension (defined by a systolic BP >=160 mm Hg and/or diastolic BP >= 100mm Hg), unstable angina, myocardial infarction within the last 4 months, or uncontrolled congestive heart failure. Subjects with a history of cardiac disease should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
  • Has a medical history or current diagnosis of myocarditis.
  • Has a left ventricular ejection fraction <50%, cardiac valvulopathy > grade 2, or elevated cardiac enzymes (troponin I) elevation > 2x ULN.
  • Has a condition/s that are considered to have a high risk of clinically significant GI bleed or any other condition associated with or history of significant bleeding.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Patients receiving physiological replacement doses of corticosteroids (10mg of prednisone or equivalent) are allowed.
  • Has known active, uncontrolled HIV (high viral load), Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Patients who have been vaccinated for hepatitis B and do not have a history of infection are eligible.
  • Has received a live vaccine within 30 days prior to the first dose of trial treatment. COVID-19 vaccination or booster is permitted any time prior to enrollment or during treatment on trial, in a manner consistent with individual institutional guidelines.
  • Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
  • Has an active serious infection requiring systemic therapy.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Subject is unable or unwilling to participate in a study related procedure.
  • 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 120 days after the last dose of trial treatment.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02215

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: A Phase 2 Study of Neoadjuvant NIS793 in Combination With mFOLFIRINOX in Resectable and Borderline Resectable Pancreatic Adenocarcinoma (PDAC)

This study is being done to evaluate the safety and efficacy of adding NIS793 to standard of care FOLFIRINOX treatment for pancreatic cancer.

The names of the study interventions involved in this study are:

  • NIS793
  • FOLFIRINOX (Folinic acid/Leucovorin, 5-Fluorouracil, Irinotecan, and Oxaliplatin)

Other interventions may include:

  • Chemoradiation Therapy
  • Surgery
Read the detailed description

This is a randomized phase 2 study evaluating the efficacy of NIS793, a TGF-beta inhibitor, when added to a standard chemotherapy program of modified FOLFIRINOX for people with previously-untreated, resectable or borderline resectable pancreatic adenocarcinoma.

The U.S. Food and Drug Administration (FDA) has not approved NIS793 as a treatment for any disease. NIS793 works by blocking a molecule called TGF-beta. TGFbeta has been shown to promote the growth of pancreatic cancer and this study is examining if the addition of a TGF-beta blocking drug will allow the chemotherapy to work better against the cancer.

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

Participants will be randomized into two groups of:

  • Arm A will receive standard chemotherapy, mFOLFIRINOX, in combination with NIS793.
  • Arm B will receive standard chemotherapy, mFOLFIRINOX.

Based on study team determination, some participants may be offered chemoradiation following completion of chemotherapy and/or surgery following either completion of chemotherapy or chemoradiation.

Study treatment is expected to last up to 16 weeks unless disease symptom worsens .

It is expected that about 45 people will take part in this research study.

Being tested
mFOLFIRINOX, 5-Fluorouracil (5-FU), Oxaliplatin, Irinotecan, Leucovorin
Keywords
Pancreatic Cancer, Resectable Pancreatic Cancer, Borderline Resectable Pancreatic Adenocarcinoma, Pancreatic Adenocarcinoma
Medical subject headings
Pancreatic Neoplasms

What participants receive

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

  • mFOLFIRINOXDrug

    Combination of the drugs 5-Fluorouracil (5-FU), Oxaliplatin, Irinotecan, and Leucovorin given by intravenous infusion

  • 5-Fluorouracil (5-FU)Drug

    Also called Adrucil

    Part of the FOLFIRINOX drug combination, given by intravenous infusion

  • OxaliplatinDrug

    Also called Eloxatin

    Part of the FOLFIRINOX drug combination, given by intravenous infusion

  • IrinotecanDrug

    Also called Camptosar, Camptothecin-11, CPT-1

    Part of the FOLFIRINOX drug combination, given by intravenous infusion

  • LeucovorinDrug

    Also called Calcium Leucovorin, Citrovorum Factor, Folinic Acid

    Part of the FOLFIRINOX drug combination, given by intravenous infusion

  • NIS793Drug

    Given by intravenous infusion

  • ChemoradiationRadiation

    Combination of Chemo (Capecitabine) and Radiation Therapy

  • SurgeryProcedure or surgery

    Surgical removal of tumor

Study groups in NCT05546411
Study groupRoleWhat they receive
mFOLFIRINOX + NIS793ExperimentalParticipants will be randomly assigned to receive: * FOLFIRINOX + NIS793 on day 1 of each 14 day cycle up to 8 cycles/16 weeks * Cycles 9+: Based on study team determination, some participants may be offered chemoradiation following completion of chemotherapy and/or surgery following either completion of chemotherapy or chemoradiation
Receives: Drug: mFOLFIRINOX; Drug: 5-Fluorouracil (5-FU); Drug: Oxaliplatin; Drug: Irinotecan; Drug: Leucovorin; Drug: NIS793; Radiation: Chemoradiation; Procedure: Surgery
mFOLFIRINOXActive comparatorParticipants will be randomly assigned to receive: * FOLFIRINOX on day 1 of each 14 day cycle up to 8 cycles/16 weeks * Cycles 9+: Based on study team determination, some participants may be offered chemoradiation following completion of chemotherapy and/or surgery following either completion of chemotherapy or chemoradiation
Receives: Drug: mFOLFIRINOX; Drug: 5-Fluorouracil (5-FU); Drug: Oxaliplatin; Drug: Irinotecan; Drug: Leucovorin; Radiation: Chemoradiation; Procedure: Surgery

What is being measured

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

  1. Major Pathological Response Rate (MPR)

    Major pathological response (MPR) defined as <5% residual tumor cells visible in the pancreatic resection specimen. The major pathological response rate will be analyzed among all patients who start protocol therapy, including those not resected due to early progression, death or off study.

    Measured: Pathology review is done in surgery assessments, once within 14 days prior to the operation.

Secondary outcomes (3)

  1. Treatment-Related Toxicity Rate

    All adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv5 as reported on case report forms will be counted. Rate is the proportion of treated participants experiencing at least one treatment-related AE of any type during the time of observation.

    Measured: Cycle 1 Day 1 through 30 days post last treatment date, up to 9 months.

  2. Median Progression-free Survival (PFS)

    Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

    Measured: From randomization (or registration) to the earlier of progression or death due to any cause, up to 9 months. Participants alive without disease progression are censored at date of last disease evaluation.

  3. Median Overall Survival (OS)

    OS is based on the Kaplan-Meier method, defined as the time from study entry to death or censored at date last known alive.

    Measured: Post treatment follow up done at least once every 12 weeks (+/- 28 days), up to 9 months.

Timeline

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

  1. First posted19 Sep 2022
  2. Study start6 Jan 2023
  3. Primary completion16 Aug 2023
  4. Study completion13 Oct 2023

Why it stopped: Novartis, the drug manufacturer of NIS793, notified Dana Farber Cancer Institute that they are stopping all clinical development of NIS793 in pancreatic cancer, effective immediately.

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
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05546411
Sponsor's protocol ID
22-314
Status last verified
Nov 2024
First submitted
7 Sep 2022
Last updated
17 Dec 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing mFOLFIRINOX, 5-Fluorouracil (5-FU) and Oxaliplatin in people with Pancreatic Cancer and Resectable Pancreatic Cancer, run by Kimberly Perez, MD at 2 sites 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 21 inclusion and 20 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: stopped early, as of the sponsor's last update on 17 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 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?

Yes. Results are posted in the registry (first posted 16 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Major Pathological Response Rate (MPR) (time frame: Pathology review is done in surgery assessments, once within 14 days prior to the operation.). 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 NCT05546411.

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 17 Dec 2024.

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