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

NCT04331041 | Active Not Recruiting Phase 2 DMC FDA Drug FDA Device

• 2 other identifiers: 202106061R01CA248917-01
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Pancreas Adenocarcinoma; Pancreas Cancer; Cancer of the Pancreas

Outcome Measures

Primary Outcomes (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).

  After completion of treatment (estimated to be 12 months)

Secondary Outcomes (6)

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

  From start of adaptive SBRT through 90 days

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

  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)

• Overall survival (Experimental Arm only)

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

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

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

• Objective response rate (Experimental Arm only)

  12-14 weeks post-adaptive SBRT

Study Arms (2)

Adaptive SBRT + Defactinib

EXPERIMENTAL

* 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.

Device: Adaptive stereotactic body radiation therapy; Drug: Defactinib; Procedure: Tumor biopsy; Procedure: Research blood draw

Adaptive SBRT

ACTIVE COMPARATOR

-Participants in this study will receive 5 fractions of magnetic resonance adaptive stereotactic body radiation therapy (SBRT)

Device: Adaptive stereotactic body radiation therapy; Procedure: Research blood draw

Interventions

Adaptive stereotactic body radiation therapy DEVICE

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

Also known as: Adaptive SBRT

Adaptive SBRT; Adaptive SBRT + Defactinib

Defactinib DRUG

-Oral drug 400 mg twice a day

Also known as: VS-6063, PF-04554878

Adaptive SBRT + Defactinib

Tumor biopsy PROCEDURE

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

Adaptive SBRT + Defactinib

Research blood draw PROCEDURE

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

Adaptive SBRT; Adaptive SBRT + Defactinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• Verastem, Inc.: collaborator
• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• 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.

  PMID: 37598000 DERIVED

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

defactinib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Carl DeSelm, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The enrolled patients are 6:1 randomized to either Experimental Arm or Adaptive Comparator Arm.

Study Record Dates

• First Submitted: March 30, 2020
• First Posted: April 2, 2020
• Study Start: August 24, 2021
• Primary Completion: February 9, 2026
• Study Completion (Estimated): April 21, 2027
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 9 months and ending 36 months following article publication.
• Access Criteria: Investigators who proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.

Locations

US (1)