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Pancreatic Ductal AdenocarcinomaPhase 1/2NUMANTIANCT04827953

Study to Evaluate the Safety and Efficacy of Treatment With NLM-001 and Standard Chemotherapy Plus Zalifrelimab in Patients With Advanced Pancreatic Cancer

A Phase 1/2 study testing Gemcitabine, Nab paclitaxel and NLM-001 in people with Pancreatic Ductal Adenocarcinoma, run by Nelum Corp at 6 sites in Spain.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

In order to improve the survival rates and decrease progression of pancreatic advanced cancer, this study aims to evaluate the first line treatment approved for this disease (gemcitabine plus nab-paclitaxel) in combination with two experimental drugs, an inhibitor of the signaling pathway of Hedgehog and an… Read more about this study

Who is it for?
Ages 18 to 90 years
Conditions the study is for
Pancreatic Ductal Adenocarcinoma
What is being tested?
Gemcitabine, Nab paclitaxel and NLM-001
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
6 sitesSpain
Study dates
1 Sep 2021to Apr 2025
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Investigators must ensure that patients are able to understand the requirements of the study and provide informed consent
  • Age ≥18 years
  • Histological or cytological diagnosis of pancreatic adenocarcinoma
  • Stage IV disease
  • No prior treatment for advanced disease. Patients who have received chemotherapy for localize disease are eligible if at least six months have elapsed from the last chemotherapy treatment
  • Measurable disease per RECIST 1.1 as determined by the investigator
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  • ECOG (Eastern Cooperative Oncology Group) PS 0-1
  • Sufficient hematopoietic, renal and liver function as defined as:
  • Neutrophil count ≥ 1.5 x 10*9 / L
  • Platelet count ≥ 100 x 10*9 / L
  • Bilirubin ≤ 1.5 x ULN (upper limit of normal)
  • AST and / or ALT ≤2.5 x ULN or ≤5 for patients with liver disease
  • Serum creatinine ≤ 1.5 x ULN
  • Tumor lesion amenable for safe repeated biopsy
  • Women of child-bearing age and men who wish to participate in the study must agree to use appropriate contraceptive methods from the signing of informed consent until 3 months after discontinuation of the study drug
  • Adequate contraception includes abstinence, oral contraceptives, transdermal patches, and injections that prolong release of a progestogen (starting at least 4 weeks prior to the administration of the investigational drug), double barrier method: condom or female condom (diaphragm or condom / vaginal) plus spermicide, intrauterine device (IUD), implant or a vaginal ring (placed at least 4 weeks prior to administration of investigational drug) or male partner sterilization (vasectomy with documentation of azoospermia) before the inclusion of the woman in the trial if the male is the only sex partner of the woman
  • Investigators must ensure that patients recruited will be able to meet all study requirements, including tumor biopsy, chemotherapy and monitoring

Who cannot join

  • Active or uncontrolled infection, disease or serious medical condition that may interfere with the patient's eligibility or treatment
  • History of psychiatric condition that would compromise the patient's ability to understand or comply with the requirements of the protocol, or the ability to provide informed consent
  • Concurrent antineoplastic therapy
  • Pregnant or lactating women
  • History of allergic reactions attributed to compounds of similar chemical structure or similar biological study drug composition
  • History of life-threatening serious adverse events to Gemcitabine or Nab-Paclitaxel
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  • Prior chemotherapy or chemo-radiation therapy for advanced pancreatic cancer
  • Patients requiring or being treated with potent CYP3A4 inhibitors and inducers
  • Other malignancies treated within the last 5 years, except in situ cervix carcinoma or nonmelanoma skin cancer
  • History of interstitial lung disease
  • Subjects with a history or presence of a known clotting disorder or difficulty achieving haemostasis will be excluded
  • Primary or secondary immunodeficiency, including immunosuppressive disease or autoimmune disease (including autoimmune endocrinopathies).
  • Note: Subjects with diabetes type 1, vitiligo, psoriasis, hypo-, or hyperthyroid disease not requiring immunosuppressive treatment are eligible. Subjects with Type 2 diabetes mellitus are allowed
  • Subjects with a known history of human immunodeficiency virus 1 and 2, human T lymphotropic virus 1.
  • Administration of anticancer medications or investigational drugs within the following intervals before the first administration of study drug:
  • A 1-week washout is permitted for palliative radiation to non- central nervous system (CNS) disease, with medical monitor approval. Subjects must also not have had radiation pneumonitis as a result of treatment and cannot participate in the study if they are on chronic corticosteroids for radiation pneumonitis Note: Bisphosphonates and denosumab are permitted medications
  • ≤7 days for prior corticosteroid treatment, with the following exceptions:
  • Use of an inhaled or topical corticosteroid is permitted
  • Corticosteroid premedication for radiographic imaging for dye allergies is permitted
  • Use of physiologic corticosteroid replacement therapy may be approved after consultation with the medical monitor
  • ≤7 days for immunosuppressive-based treatment for any reason, with the exceptions noted above for prior corticosteroid treatment
  • ≤21 days or 5 half-lives before first dose of study treatment for all other investigational study drugs or devices. For investigational agents with long half-lives (e.g., >5 days), enrollment before the fifth half-life requires medical monitor approval
  • Has not recovered to grade ≤1 from toxic effects of prior therapy and/or complications from prior surgical intervention before starting therapy Note: Subjects with grade ≤2 neuropathy and alopecia are an exception and may enroll
  • History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful
  • Concurrent participation in other investigational drug trials
  • Known central nervous system (CNS) involvement as follows:
  • Untreated CNS metastases.
  • Leptomeningeal metastases. Note: Patients may be eligible if CNS metastases have been treated and patients have neurologically returned to baseline (except for residual signs and symptoms related to the CNS treatment).

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

Spain6 sites

  • Hospital Universitari Vall d'Hebron

    Barcelona, Catalonia, 08035

  • Hospital Universitario Donostia

    Donostia / San Sebastian, Basque Country, 20014

  • Hospital Universitario Virgen De La Victoria

    Málaga, Andalusia, 29010

  • Hospital Universitario Marqués del Valdecilla

    Santander, 39008

  • Hospital Clínico Universitario de Santiago

    Santiago de Compostela, A Coruña, 15706

  • Hospital Universitario Miguel Servet

    Zaragoza, Aragon, 50009

Other trials in Spain

About this study

Official title: Phase Ib/IIa Study to Evaluate Safety and Efficacy of Treatment With the Hedgehog Inhibitor NLM-001 and Chemotherapy (Gemcitabine and Nab-Paclitaxel) Plus Zalifrelimab as First Line Treatment in Patients With Advanced Pancreatic Cancer

In order to improve the survival rates and decrease progression of pancreatic advanced cancer, this study aims to evaluate the first line treatment approved for this disease (gemcitabine plus nab-paclitaxel) in combination with two experimental drugs, an inhibitor of the signaling pathway of Hedgehog and an immunotherapy drug able of blocking the CTLA-4 receptor.

Read the detailed description

Pancreatic cancer is one of the leading neoplasms in the world in terms of mortality, with very low survival rates mainly due to its rapid progression and diagnosis in advanced stages, which makes its treatment extremely difficult.

Gemcitabine plus nab-paclitaxel is currently considered the first-line standard treatment for advanced pancreatic cancer due to this superiority against other treatments.

In order to find an alternative to improve survival of advanced pancreatic cancer, this study aims to evaluate the efficacy with first-line treatment in combination of two experimental drugs, a Hedgehog pathway inhibitor (NLM-001) and a CTLA-4 blocker (zalifrelimab) in previously untreated patients with advanced pancreatic cancer.

Being tested
Gemcitabine, Nab paclitaxel, NLM-001, Zalifrelimab

What participants receive

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

  • GemcitabineDrug

    Gemcitabine 1000 mg/m2 IV on days 1, 8 and 15 (conventional chemotherapy).

  • Nab paclitaxelDrug

    Nab-Paclitaxel 125 mg/m2 IV on days 1, 8 and 15 (conventional chemotherapy).

  • NLM-001Drug

    NLM-001 will be administered three cycles consecutively followed by two rest cycles.

  • ZalifrelimabDrug

    Zalifrelimab administration each 6 weeks.

Study groups in NCT04827953
Study groupRoleWhat they receive
Investigational treatmentExperimentalConventional Chemotherapy (Gemcitabine + nab-paclitaxel) plus NLM-001 plus Zalifrelimab
Receives: Drug: Gemcitabine; Drug: Nab paclitaxel; Drug: NLM-001; Drug: Zalifrelimab

What is being measured

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

  1. Treatment efficacy according to response

    Objective Response Rate (ORR): Complete Response (CR) + Partial Response (PR) according to RECIST 1.1 criteria

    Measured: 17 months

Secondary outcomes (12)

  1. Frequency of occurrence of adverse events

    Frequency of occurrence of adverse events according to NCI-CTCAE v5.0 criteria

    Measured: 8 months

  2. Treatment efficacy according to disease control rate

    Disease Control Rate (DCR): Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) evaluated by RECIST 1.1 criteria

    Measured: 8 months

  3. Treatment efficacy according to progression free survival (PFS)

    Time in months from the patient's study enrolment until patient progression according to RECIST 1.1 criteria or death.

    Measured: 8 months

  4. Treatment efficacy according to Duration of Response (DoR)

    Time between the date of first confirmed response to the date of the first documented tumor progression (per RECIST 1.1), or death due to any cause, whichever occurs first

    Measured: 8 months

  5. Treatment efficacy according to Overall Survival (OS)

    Time in months since the patient's study enrolment until death.

    Measured: 8 months

  6. CA 19.9

    Decrease in CA 19.9 levels > 50%

    Measured: 8 months

  7. Gli mRNA and SMA + CAF expression and ORR

    Correlation between change in Gli mRNA and SMA + CAF expression and Objective Response Rate (ORR).

    Measured: 1 month

  8. Gli mRNA and SMA + CAF expression and PFS

    Correlation between change in Gli mRNA and SMA + CAF expression and Progression Free Survival (PFS).

    Measured: 1 month

  9. Collagen structure and ORR

    Correlation between change in Collagen structure and Objective Response Rate (ORR)

    Measured: 1 month

  10. Collagen structure and PFS

    Correlation between change in Collagen structure and Progression Free Survival (PFS).

    Measured: 1 month

  11. Lymphocyte infiltration and ORR

    Correlation between change in lymphocyte infiltration and Objective Response Rate (ORR).

    Measured: 1 month

  12. Lymphocyte infiltration and PFS

    Correlation between change in lymphocyte infiltration and Progression Free Survival (PFS).

    Measured: 1 month

Timeline

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

  1. First posted1 Apr 2021
  2. Study start1 Sep 2021
  3. Primary completionApr 2025 (estimated)
  4. Study completionApr 2025 (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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04827953
Sponsor's protocol ID
NLM-2020-01 / NUMANTIA
Other IDs
2020-004932-52
Acronym
NUMANTIA
Status last verified
Dec 2024
First submitted
30 Mar 2021
Last updated
30 Dec 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • McAndrews KM, Mahadevan KK, Kalluri R. Mouse Models to Evaluate the Functional Role of the Tumor Microenvironment in Cancer Progression and Therapy Responses. Cold Spring Harb Perspect Med. 2024 Jul 1;14(7):a041411. doi: 10.1101/cshperspect.a041411.

    PubMed 38191175

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Gemcitabine, Nab paclitaxel and NLM-001 in people with Pancreatic Ductal Adenocarcinoma, run by Nelum Corp at 6 sites in Spain.

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 28 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: under way, not looking for participants, as of the sponsor's last update on 30 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 6 sites in Spain. 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 combined 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.

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?

This study is still under way. Results are not available in the source record yet.

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?

Treatment efficacy according to response (time frame: 17 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 NCT04827953, which also lists 1 linked publication.

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 30 Dec 2024.

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