Study of Neo-adjuvant RO7009789 Alone or Neo-adjuvant RO7009789 Plus Nab-Paclitaxel and Gemcitabine Followed by Adjuvant RO7009789 Plus Nab-Paclitaxel and Gemcitabine for Patients With Newly Diagnosed Resectable Pancreatic Carcinoma

• ClinicalTrials.gov Identifier: NCT02588443
• Recruitment Status: Completed
• First Posted: October 27, 2015
• Last Update Posted: April 16, 2019
• Sponsor: Abramson Cancer Center of the University of Pennsylvania
• Information provided by (Responsible Party): Abramson Cancer Center of the University of Pennsylvania

Study Description

Brief Summary:

The main purpose of this study is to learn if adding the investigational drug RO7009789 (anti-CD40) to nab-paclitaxel and gemcitabine both before surgery and after surgery is safe, feasible, and beneficial to patients with pancreatic cancer. This study also intends to look at blood and tissue samples to help doctors better understand the role of the immune system in fighting cancer.

Condition or disease	Intervention/treatment	Phase
Pancreatic Cancer	Drug: RO70097890; Drug: nab-paclitaxel; Drug: gemcitabine	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Intervention Model: Parallel Assignment
• Primary Purpose: Treatment
• Official Title: Phase I Study of Neo-adjuvant RO7009789 Alone or Neo-adjuvant RO7009789 Plus Nab-Paclitaxel and Gemcitabine Followed by Adjuvant RO7009789 Plus Nab-Paclitaxel and Gemcitabine for Patients With Newly Diagnosed Resectable Pancreatic Carcinoma
• Actual Study Start Date: October 2015
• Actual Primary Completion Date: November 2018
• Actual Study Completion Date: November 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm1; Arm I provides one dose of RO70097890 as a single agent in the neoadjuvant setting. Patients will recover from any toxicities and will then have their disease surgically resected. After recovery from surgery patients will proceed to adjuvant therapy which will include nab-paclitaxel 125mg/m2 and gemcitabine 1000mg/m2 on days 1,8 and 15 of a 28 day cycle along with RO7009789 0.2mg/kg on day 3 of each cycle. Four cycles of adjuvant therapy will be given. All medications are administered intravenously.	Drug: RO70097890; Drug: nab-paclitaxel; Drug: gemcitabine
Experimental: Arm2; Arm II provides one dose of RO7009789 two days after one dose of nab-paclitaxel and one dose of gemcitabine prior to surgery. Nab-paclitaxel and gemcitabine are given on day 1. RO7009789 will be given on day 3. Patients will recover from any toxicities and will then have their disease surgically resected. Patients will receive four cycles of these same medications in an adjuvant fashion after recovering from surgical resection. A cycle will consist of nab-paclitaxel (125mg/m²), gemcitabine (1000mg/m²) given on days 1,8 and 15 of a 28 day cycle along with RO7009789 0.2mg/kg on day 3 of each cycle.	Drug: RO70097890; Drug: nab-paclitaxel; Drug: gemcitabine

Outcome Measures

Primary Outcome Measures :

1. Number of Adverse Events [ Time Frame: 2 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Histological documentation of primary adenocarcinoma of the pancreas
• Surgically eligible for tumor resection with curative intent
• Age ≥18 years
• ECOG PS 0 or 1
• Adequate bone marrow function (ANC ≥1,500; Hgb >9; Plt >100)
• Adequate renal function (Cr <1.5 ULN)
• Total bilirubin ≤1.5 x ULN; and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2.5 x ULN (values post biliary stenting allowed for eligibility).
• Signed, written informed consent

Exclusion Criteria:

• Non ductal adenocarcinomas, neuroendocrine neoplasms, cystic tumors of the pancreas such as cystadenomas, cystadenocarcinomas and solid pseudopapillary neoplasms. In addition, adenocarcinomas arising from duodenum, distal bile duct, and ampulla will also be excluded.
• Patients with M1 disease or a history of M1 disease.
• Patients with any type of recurrent pancreatic adenocarcinoma
• Prior therapy such as chemotherapy or radiation therapy or anti-tumor experimental therapy for pancreatic cancer
• Previous treatment with any other compound that targets CD40
• Concurrent treatment with any anticancer agent outside of this protocol
• Prior allogeneic bone marrow transplant
• History of autoimmune disorder, including type 1 diabetes mellitus, pemphigus vulgaris, systemic mastocytosis, systemic lupus erythromatosis, dermatomyositis/polymyositis, rheumatoid arthritis, systemic sclerosis, Sjörgen's syndrome, vasculitis/arteritis, Behcet's syndrome, autoimmune thyroiditis, multiple sclerosis, or uveitis,. (Vitiligo is allowed)
• History (within the previous year) of stroke or transient ischemic attack, unstable angina, myocardial infarction, congestive heart failure
• History of deep venous thrombosis or migratory thrombophlebitis (Trousseau);
• Hereditary or acquired coagulopathies (e.g., hemophilia, von Willebrand disease, or cancer-associated DIC)
• Prior allergic reactions attributed to other monoclonal antibodies
• Concurrent or planned concurrent treatment with systemic high dose (immunosuppressive) corticosteroids or treatment with systemic corticosteroids within 4 weeks of baseline
• Treatment on another therapeutic clinical trial within 4 weeks of enrollment in this trial
• Concurrent or planned concurrent treatment with anticoagulants such as Coumadin or heparin, except to maintain patency of in-dwelling catheters
• Ongoing or active infection; treatment with systemic antibiotics or antifungals for ongoing or recurrent infection (topical use of antibiotics or antifungals is allowed)
• Pregnancy or breast-feeding - female patients must be surgically sterile, be post-menopausal, or must agree to use effective contraception during the period of therapy and for 90 days following the last dose of RO7009789. All female patients with reproductive potential must have a negative pregnancy test prior to enrollment. Women or men of reproductive potential may not participate unless they agree to use an effective contraceptive method. Female patients should not become pregnant while participating in this research study or for 90 days following therapy. Male patients should not father a child while in this research study or for 90 days following therapy.
• Other uncontrolled, concurrent illness that would preclude study participation; or, psychiatric illness or social challenges that would entail unreasonable risk or preclude informed consent or compliance with study procedures

Contacts and Locations

Locations

United States, Pennsylvania

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

Abramson Cancer Center of the University of Pennsylvania

Investigators

• Principal Investigator: Robert Vonderheide, MD, DPhil; Abramson Cancer Center of the University of Pennsylvania

More Information

• Responsible Party: Abramson Cancer Center of the University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT02588443
• Other Study ID Numbers: UPCC 20214
• First Posted: October 27, 2015
• Last Update Posted: April 16, 2019
• Last Verified: April 2019

Additional relevant MeSH terms:

Pancreatic Neoplasms; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Gemcitabine; Paclitaxel; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs