Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Symptoms and General Pathology

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Tissue Adhesions

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Gastrointestinal Agents

All Drugs and Chemicals

Pancrelipase

Pancreatin

* 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.

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

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

Adaptive stereotactic body radiation therapy

Defactinib

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

Tumor biopsy

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

Research blood draw

Hyun Kim, M.D.

Julie Schwarz, M.D., Ph.D.

David DeNardo, Ph.D.

Pamela Samson, M.D.

Carl DeSelm, M.D., Ph.D.

Allen Mo, M.D., Ph.D.

Ryan Fields, M.D.

Natasha Leigh, M.D.

Roheena Panni, M.D., Ph.D.

Majella Doyle, M.D.

Adeel Khan, M.D.

William Chapman, M.D.

Dominic Sanford, M.D.

Kian-Huat Lim, M.D., Ph.D.

Katrina Pedersen, M.D.

Benjamin Tan, M.D.

Rama Suresh, M.D.

Patrick Grierson, M.D.

Nikolaos Trikalinos, M.D.

Vladimir Kushnir, M.D.

Gabriel Lang, M.D.

Dan Mullady, M.D.

Koushik Das, M.D.

Esther Lu, Ph.D.

Olivia Aranha, M.D.

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 first 6 patients randomized to the experimental arm will be considered the safety lead-in and will be assessed for dose-limiting toxicities (DLTs). The 6 patients randomized to the control arm will be evaluated for correlatives but will not be included in the analysis for primary and secondary endpoints.

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

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

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

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.

* 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).

-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.

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

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

-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.

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

National Cancer Institute (NCI)

Verastem, Inc.

Washington University School of Medicine

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Stereotactic Body Radiotherapy and Focal Adhesion Kinase Inhibitor in Advanced Pancreas Adenocarcinoma	NCT04331041	Pancreas Cancer Cancer of the P... Pancreas Adenoc...	Adaptive stereo... Defactinib Tumor biopsy Research blood ...	18 Years -	Washington University School of Medicine
Stereotactic Body Radiotherapy and Focal Adhesion Kinase Inhibitor in Advanced Pancreas Adenocarcinoma	NCT04331041	Pancreas Cancer Cancer of the P... Pancreas Adenoc...	Adaptive stereo... Defactinib Tumor biopsy Research blood ...	18 Years -	Washington University School of Medicine

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