NCT03599362

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

Terminated Phase 2 Results posted Last updated 19 October 2021

What this trial tests

Phase 2 trial testing Nivolumab + Cabiralizumab in Pancreatic Cancer in 7 participants. Terminated before completion.

Timeline

31 July 2018

Primary endpoint
15 June 2020

15 June 2020

Quick facts

Lead sponsor	NYU Langone Health
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	7
Start date	31 July 2018
Primary completion	15 June 2020
Estimated completion	15 June 2020
Sites	2 locations across United States

Drugs / interventions tested

• Nivolumab + Cabiralizumab — full drug profile →
• Stereotactic Body Radiotherapy (SBRT) — full drug profile →

Conditions studied

• Pancreatic Cancer — all drugs for Pancreatic Cancer →

Sponsor

NYU Langone Health — full company profile →

Who can join

Adults 18 to 100, any sex, with Pancreatic Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Incidence of Unacceptable Toxicity Primary · 24 Months

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

Group	Value	95% CI
Multi Agent Chemotherapy Cancer Patients	4

Number of Participants Who Proceeded to Surgical Resection Primary · 24 Months

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

Group	Value	95% CI
Multi Agent Chemotherapy Cancer Patients	1

Adverse events — posted to ClinicalTrials.gov

Time frame: 24 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Multi Agent Chemotherapy Cancer Patients

Serious: 3/4 (75%)

Deaths: 2/4

Serious adverse events (4 terms)

Reaction	System	Multi Agent Chemotherapy C…
Liver dysfunction	Hepatobiliary disorders	—
Chest Pain	Cardiac disorders	—
Hypertension	Vascular disorders	—
Aspiration	Respiratory, thoracic and mediastinal disorders	—

Other adverse events (46 terms — click to expand)

Reaction	System	Multi Agent Chemotherapy C…
Increase in ALT	Investigations	—
Increase in AST	Investigations	—
Increase in CPK	Investigations	—
Increase in Lipase	Investigations	—
Increase in Alkaline Phosphatase	Investigations	—
Back Pain	Musculoskeletal and connective tissue disorders	—
Decrease in Lymphocyte Count	Investigations	—
Nausea	Gastrointestinal disorders	—
Abdominal Pain	Gastrointestinal disorders	—
Anemia	Blood and lymphatic system disorders	—
Anorexia	Metabolism and nutrition disorders	—
Chills	General disorders	—
Constipation	Gastrointestinal disorders	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—
Fall	Injury, poisoning and procedural complications	—
Gastritis	Gastrointestinal disorders	—
Headache	Nervous system disorders	—
Decrease in Platelet Count	Investigations	—
Rash Maculo	Skin and subcutaneous tissue disorders	—
Increase in Serum Amylase	Investigations	—
Agitation	Psychiatric disorders	—
Bloating	Gastrointestinal disorders	—
Bruising	Injury, poisoning and procedural complications	—
Confusion	Psychiatric disorders	—
Increase in Creatinine	Investigations	—
Diarrhea	Gastrointestinal disorders	—
Dry Mouth	Gastrointestinal disorders	—
Dizziness	Nervous system disorders	—
Ear and Labyrinth Disorder	Ear and labyrinth disorders	—
Ear Pain	Ear and labyrinth disorders	—
Edema Face	General disorders	—
Epis Taxis	Respiratory, thoracic and mediastinal disorders	—
Fatigue	General disorders	—
Gait Disturbance	General disorders	—
General Disorders and Administration Site Conditions	General disorders	—
Hyperuricemia	Metabolism and nutrition disorders	—
Hypoalbuminemia	Investigations	—
Hyponatremia	Investigations	—
Localized Edema	General disorders	—
Pain in Extremity	Musculoskeletal and connective tissue disorders	—

Most-reported serious reactions: Liver dysfunction, Chest Pain, Hypertension, Aspiration.

Data from ClinicalTrials.gov NCT03599362 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Challenges and Opportunities for Pancreatic Cancer Immunotherapy.
   Bear AS, Vonderheide RH, O'Hara MH. · · 2020 · cited 500× · PMID 32946773 · DOI 10.1016/j.ccell.2020.08.004
2. The Evasion Mechanisms of Cancer Immunity and Drug Intervention in the Tumor Microenvironment.
   Kim SK, Cho SW. · · 2022 · cited 300× · PMID 35685630 · DOI 10.3389/fphar.2022.868695
3. A narrative review of tumor-associated macrophages in lung cancer: regulation of macrophage polarization and therapeutic implications.
   Sedighzadeh SS, Khoshbin AP, Razi S, Keshavarz-Fathi M, et al · · 2021 · cited 160× · PMID 34012800 · DOI 10.21037/tlcr-20-1241
4. TAMing pancreatic cancer: combat with a double edged sword.
   Lankadasari MB, Mukhopadhyay P, Mohammed S, Harikumar KB. · · 2019 · cited 84× · PMID 30925924 · DOI 10.1186/s12943-019-0966-6
5. Targeting of TAMs: can we be more clever than cancer cells?
   Kzhyshkowska J, Shen J, Larionova I. · · 2024 · cited 79× · PMID 39516356 · DOI 10.1038/s41423-024-01232-z
6. Tumor-Associated Macrophages in Pancreatic Ductal Adenocarcinoma: Therapeutic Opportunities and Clinical Challenges.
   Poh AR, Ernst M. · · 2021 · cited 79× · PMID 34201127 · DOI 10.3390/cancers13122860
7. Role of Tumor-Mediated Dendritic Cell Tolerization in Immune Evasion.
   DeVito NC, Plebanek MP, Theivanthiran B, Hanks BA. · · 2019 · cited 72× · PMID 31921140 · DOI 10.3389/fimmu.2019.02876
8. The Interplay of the Extracellular Matrix and Stromal Cells as a Drug Target in Stroma-Rich Cancers.
   Kozlova N, Grossman JE, Iwanicki MP, Muranen T. · · 2020 · cited 66× · PMID 32014341 · DOI 10.1016/j.tips.2020.01.001