Study of Nivolumab, Cabiralizumab, and Stereotactic Body Radiotherapy (SBRT) for Locally Advanced Unresectable Pancreatic Cancer

NCT03599362 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-01430
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

Brief Summary

A multi-institutional, single arm phase II study of nivolumab, cabiralizumab and stereotactic body radiotherapy (SBRT) in patients with LAUPC. The purpose of this study is to determine the safety and tolerability of combined cabiralizumab, nivolumab and radiotherapy in the treatment of locally advanced pancreatic cancer. Investigators will also estimate the surgical resection rate following treatment with combined cabiralizumab, nivolumab and radiotherapy in subjects with locally advanced unresectable pancreatic cancer.

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Incidence of Unacceptable Toxicity

  Measure of safety of combined cabiralizumab, nivolumab and radiotherapy in the treatment of locally advanced pancreatic cancer measured by unacceptable toxicity, which includes: * Grade 3 fatigue lasting \> 2 Weeks * Grade 3 Nausea lasting \> 7 days despite maximal medical management * Grade 3 or more anorexia * Grade 3 or more vomiting * Grade 3 or more diarrhea * Grade 3 or more pancreatitis * Grade 3 abdominal pain * Grade 3 or more radiation dermatitis * Grade 3 or more GI hemorrhage * Grade 3 or more GI fistula * Grade 3 or more GI stenosis * Grade 3 or more GI perforation

  24 Months

• Number of Participants Who Proceeded to Surgical Resection

  Surgical resection rate following treatment with combined cabiralizumab, nivolumab and radiotherapy in subjects with locally advanced unresectable pancreatic cancer. This will be measured by tabulating adverse events

  24 Months

Study Arms (1)

Multi Agent Chemotherapy Cancer Patients

EXPERIMENTAL

Subjects will be enrolled into this study following completion of 2-6 months of multi agent chemotherapy with documentation of stable or responsive disease.

Drug: Nivolumab + Cabiralizumab; Radiation: Stereotactic Body Radiotherapy (SBRT)

Interventions

Nivolumab + Cabiralizumab DRUG

Will be administered on Day 1 and Day 14; Subjects will continue treatment every 2 weeks with subsequent imaging every 8 weeks.

Multi Agent Chemotherapy Cancer Patients

Stereotactic Body Radiotherapy (SBRT) RADIATION

Patients will be simulated supine with the addition of a 4D C T if appropriate. A stereotactic immobilization device with abdominal compression will be used.

Multi Agent Chemotherapy Cancer Patients

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed locally advanced, unresectable pancreatic cancer as defined by NCCN Guidelines 3.2017
• Locally advanced unresectable disease is defined by the NCCN as:
• Tumors of the head that have greater than 180 degrees of SMA encasement or any celiac abutment, unreconstructable SMV or portal occlusion, or aortic invasion or encasement.
• Tumors of the body with SMA or celiac encasement of greater than 180 degrees, unreconstructable SMV or portal occlusion, or aortic invasion.
• Tumors of the tail with SMA or celiac encasement of greater than 180 degrees. Irrespective of location, all tumors with evidence of nodal metastasis outside of the resection field are deemed unresectable.
• Patients must agree to pretreatment and on treatment tumor biopsy
• ECOG performance status of 0 or 1
• Completion of at least 2 months, but no more than 6 months of standard induction chemotherapy for LAPC, which must include either FOLFIRINOX or gemcitabine and nab- paclitaxel, preferably within 2-4 weeks but no longer than 8 weeks.
• Normal organ and marrow function as defined below:
• absolute neutrophil count ≥ 1,500/mm3
• platelets ≥ 100,000/mm3
• total bilirubin ≤ 1.5 x institutional upper limit of normal (except participants with Gilbert's syndrome who must have normal direct bilirubin)
• AST(SGOT) and ALT(SGPT) ≤ 2 × institutional upper limit of normal
• creatinine ≤ 1.5 mg/ dL OR
• creatinine clearance≥ 30 mL/min (as estimated by Cockcroft Gault Equation)

You may not qualify if:

• Resectable, borderline resectable or metastatic disease
• Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity.
• Participants with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study treatment administration except for adrenal replacement steroid doses \> 10 mg daily prednisone equivalent in the absence of active autoimmune disease.
• Note: Treatment with a short course of steroids (\< 5 days) up to 7 days prior to initiating study treatment is permitted.
• Current or history of clinically significant muscle disorders (eg, myositis), recent unresolved muscle injury, or any condition known to elevate serum CK levels
• Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:
• Myocardial infarction or stroke/transient ischemic attack within the past 6 months
• Uncontrolled angina within the past 3 months
• Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
• History of other clinically significant heart disease (eg, cardiomyopathy, congestive heart failure with New York Heart Association functional classification III to IV, pericarditis, significant pericardial effusion, or myocarditis)
• Cardiovascular disease-related requirement for daily supplemental oxygen therapy.
• Evidence of uncontrolled, active infection, requiring parenteral anti-bacterial, anti-viral or anti-fungal therapy ≤ 7 days prior to administration of study medication.
• Any uncontrolled inflammatory GI disease including Crohn's Disease and ulcerative colitis.
• Participants with active, known, or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, euthyroid participants with a history of Grave's disease (participants with suspected autoimmune thyroid disorders must be negative for thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin prior to first dose of study treatment), psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll after discussing with the Principal Investigator.
• Concomitant use of statins while on study. However, a patient using statins for over 3 months prior to study drug administration and in stable status without CK rise may be permitted to enroll.

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (2)

New York University School of Medicine

New York, New York, 10016, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Nivolumab; cabiralizumab; Radiosurgery

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Fraustina Hsu
• Organization: NYU Langone Health

Fraustina.Hsu@nyulangone.org

6467547124

Study Officials

• Deirdre Cohen, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: July 10, 2018
• First Posted: July 26, 2018
• Study Start: July 31, 2018
• Primary Completion: June 15, 2020
• Study Completion: June 15, 2020
• Last Updated: October 19, 2021
• Results First Posted: October 19, 2021

Record last verified: 2021-09

Locations

US (2)