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Pancreas CancerPhase 2NCT04331041

Stereotactic Body Radiotherapy and Focal Adhesion Kinase Inhibitor in Advanced Pancreas Adenocarcinoma

A Phase 2 study testing Adaptive stereotactic body radiation therapy, Defactinib and Tumor biopsy in people with Pancreas Cancer and Cancer of the Pancreas, run by Washington University School of Medicine at 1 site in United States.

Active, not recruiting

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

Official record
Search all trials

Trial summary

Patients with advanced pancreas adenocarcinoma will be randomized on a 6:1 basis to receive standard of care chemotherapy followed by adaptive stereotactic body radiotherapy (SBRT) with concurrent and adjuvant FAK inhibitor defactinib (experimental arm) or standard of care chemotherapy followed by SBRT (control arm). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Adaptive stereotactic body radiation therapy, Defactinib and Tumor biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
1 siteUnited States
Study dates
24 Aug 2021to 21 Apr 2027
Phase
Phase 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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically confirmed locally advanced pancreas adenocarcinoma that is considered borderline resectable or unresectable per institutional standardized criteria of unresectability or medical inoperability (NCCN guidelines 2.2021 PANC-C 1 of 2).
  • Patients with locoregional adenopathy are eligible as long as all suspicious lymph nodes are deemed to be adjacent to the primary tumor as per radiation oncologist assessment.
  • At least 3 months of systemic chemotherapy for this disease without progression of local or systemic disease. Newly diagnosed patients may be screened for enrollment in this study and can be enrolled once they have completed 3 months of systemic chemotherapy (and still meet all eligibility criteria) prior to the start of study treatment.
  • At least 18 years of age.
  • ECOG performance status ≤ 1
  • Life expectancy > 3 months
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  • Normal bone marrow and organ function within 21 days of randomization as defined below:
  • Absolute neutrophil count ≥ 1,500/mcL
  • Platelets ≥ 100,000/mcL
  • Hemoglobin ≥ 9.0 g/dL
  • Total bilirubin ≤ 1.5 x IULN; no prior history of Gilbert's syndrome
  • AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN or ≤ 5.0 x IULN if due to liver involvement by tumor
  • Creatinine clearance ≤ 1.5 x IULN or glomerular filtration rate of ≥ 60 mL/min
  • INR ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as INR or PTT is within therapeutic range of intended use of anticoagulants
  • aPTT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as INR or PTT is within therapeutic range of intended use of anticoagulants
  • Albumin ≥ 2.5 mg/dL
  • Corrected QT interval (QTc) < 480 ms (as calculated by the Fridericia correction formula).
  • The effects of defactinib on the developing human fetus are unknown. For this reason and because radiation therapy is known to be teratogenic, women of childbearing potential and men must agree to use highly effective 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. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and 120 days after completion of the study
  • Ability to understand and willingness to sign an IRB approved written informed consent document

Who cannot join

  • A history of other malignancy with the exception of malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease.
  • Clinical evident ascites or pleural effusion that requires therapeutic paracentesis or thoracentesis.
  • Prior treatment with a drug of the FAK inhibitor class or with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
  • Prior anti-human antibody response (AHA or ADA).
  • Currently receiving any other investigational agents or has receive any other investigational agents within 4 weeks or 5 half-lives or planned first dose of study agents.
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to defactinib or other agents used in the study.
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  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy not routinely associated with chemotherapeutic regimen.
  • Requires continued use of warfarin for anticoagulation and cannot stop warfarin or be safely switched to another anticoagulant or direct oral anticoagulant
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, hypertension, immunosuppression, autoimmune conditions, or underlying pulmonary disease.
  • Has an active autoimmune disease requiring systemic treatment within the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Received a live vaccine within 30 days prior to the first study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist) are live attenuated vaccines and are not allowed.
  • Known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected).
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  • Has a known history of active TB (bacillus tuberculosis).
  • Major surgery within 28 days prior to the first study treatment.
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
  • Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended.
  • Known SARS-Cov2 infection ≤28 days prior to first dose of study therapy.
  • Exposure to P-glycoprotein (P-gp) inhibitors or inducers within 14 days prior to the first dose and during the course of therapy.
  • Subjects with the inability to swallow oral medications or impaired gastrointestinal absorption due to gastrectomy or active inflammatory bowel disease.
  • Subjects with a history of hypersensitivity to any of the inactive ingredients (hydroxypropylmethylcellulose, mannitol, magnesium stearate) of the investigational product.

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: Phase II Study of Stereotactic Body Radiotherapy and Focal Adhesion Kinase Inhibitor in Advanced Pancreas Adenocarcinoma

Patients with advanced pancreas adenocarcinoma will be randomized on a 6:1 basis to receive standard of care chemotherapy followed by adaptive stereotactic body radiotherapy (SBRT) with concurrent and adjuvant FAK inhibitor defactinib (experimental arm) or standard of care chemotherapy followed by SBRT (control arm). Patients enrolled to the experimental arm will be assessed for clinical outcomes such as progression free survival (PFS), local control, distant control, and toxicity. The initial 6 patients randomized to the experimental arm will be considered the safety lead-in and will be assessed for dose-limiting toxicities (DLTs). Following completion of the safety lead-in, additional patients will be accrued in order to reach a total of 36 patients on the experimental arm (inclusive of the safety lead-in cohort) and 6 on the control arm.

Being tested
Adaptive stereotactic body radiation therapy, Defactinib, Tumor biopsy, Research blood draw
Medical subject headings
Pancreatic Neoplasms

What participants receive

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

  • Adaptive stereotactic body radiation therapyDevice

    Also called Adaptive SBRT

    • Will be administered using MRIdian and Ethos
    • 50 Gy in 5 fractions

  • DefactinibDrug

    Also called VS-6063, PF-04554878

    -Oral drug 400 mg twice a day

  • Tumor biopsyProcedure or surgery

    -Baseline and 12-14 weeks after end of SBRT (or at time of surgery)

  • Research blood drawProcedure or surgery

    -Baseline, 6-8 weeks after the end of SBRT, and 12-14 weeks after the end of SBRT

Study groups in NCT04331041
Study groupRoleWhat they receive
Adaptive SBRT + DefactinibExperimental* Participants in this study will receive 5 fractions of magnetic resonance adaptive stereotactic body radiation therapy (SBRT) and seventeen 21-day cycles of defactinib (beginning on Day 2 of radiation). * Participants who are candidates for surgical resection will undergo standard of care surgery at 2 weeks post-end of SBRT (+/- 1 weeks) or 12 weeks post-end of SBRT (+/- 1 week). These participants will discontinue defactinib the day prior to the operation and will resume taking it for the remainder of the 17 cycles 4 to 6 weeks after surgery. Participants who are not candidates for surgical resection will continue to receive defactinib uninterrupted. All participants should receive 17 cycles of defactinib unless they experience disease progression or intolerable toxicity.
Receives: Device: Adaptive stereotactic body radiation therapy; Drug: Defactinib; Procedure: Tumor biopsy; Procedure: Research blood draw
Adaptive SBRTActive comparator-Participants in this study will receive 5 fractions of magnetic resonance adaptive stereotactic body radiation therapy (SBRT)
Receives: Device: Adaptive stereotactic body radiation therapy; Procedure: Research blood draw

What is being measured

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

  1. Progression-free survival (PFS) (Experimental Arm only)

    • PFS is defined as the duration of time from start of standard of care chemotherapy treatment to time of progression or death, whichever occurs first. The alive patients without progression will be censored at the last follow-up.
    • Progressive disease: 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: After completion of treatment (estimated to be 12 months)

Secondary outcomes (6)

  1. Number of participants with acute adverse events (Experimental Arm only)

    -The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.

    Measured: From start of adaptive SBRT through 90 days

  2. Number of participants with late adverse events (Experimental Arm only)

    -The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.

    Measured: From 91 days through 12 months post-SBRT, or through 90 days after the last dose of defactinib, whichever comes first (estimated to be 12 months and 5 days)

  3. Overall survival (Experimental Arm only)

    -Overall survival as defined as the time from the date of treatment until death; censored at last follow-up if death is not observed

    Measured: Through completion of follow-up (estimated to be 24 months)

  4. Distant metastasis progression-free survival (DM-PFS) (Experimental Arm only)

    -Defined as the days from the date of the treatment to distant metastasis progression or death

    Measured: Through completion of follow-up (estimated to be 24 months)

  5. Objective response rate (Experimental Arm only)

    -Objective response rate as determined by RECIST 1.1 criteria, with one change. Patients who undergo resection will be considered to have a CR if there is a pathologic complete response (pCR) on the surgical specimen. After resection, patients will no longer be evaluated for ORR.

    Measured: 12-14 weeks post-adaptive SBRT

  6. Local control (Experimental Arm only)

    -Local control as defined by no progression of the primary tumor by RECIST 1.1 criteria

    Measured: Through completion of follow-up (estimated to be 24 months)

Timeline

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

  1. First posted2 Apr 2020
  2. Study start24 Aug 2021
  3. Primary completion9 Feb 2026
  4. Study completion21 Apr 2027 (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
Model description
The enrolled patients are 6:1 randomized to either Experimental Arm or Adaptive Comparator Arm.
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04331041
Sponsor's protocol ID
202106061
Other IDs
R01CA248917-01
Status last verified
May 2026
First submitted
30 Mar 2020
Last updated
8 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
Individual data sharing
Yes: Sharing of individual participant data that underlie the results reported in the article after deidentification (text, tables, figures, and appendices) for individual participant data meta-analysis.

Publications

  • Fard D, Giraudo E, Tamagnone L. Mind the (guidance) signals! Translational relevance of semaphorins, plexins, and neuropilins in pancreatic cancer. Trends Mol Med. 2023 Oct;29(10):817-829. doi: 10.1016/j.molmed.2023.07.009. Epub 2023 Aug 17.

    PubMed 37598000

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Adaptive stereotactic body radiation therapy, Defactinib and Tumor biopsy in people with Pancreas Cancer and Cancer of the Pancreas, 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 19 inclusion and 21 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 8 May 2026. 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 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?

Progression-free survival (PFS) (Experimental Arm only) (time frame: After completion of treatment (estimated to be 12 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 NCT04331041, 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 8 May 2026.

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