Study Evaluating NEOadjuvant Immunotherapy in Resectable PANCreatic Ductal Adenocarcinoma

NCT03979066 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: AAAS1908
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if study treatment with atezolizumab and PEGPH20 given before and after surgery, followed by chemotherapy is safe and if it can further increase the immune response against the tumor rather than increase the chance of cure.

Conditions

Pancreatic Ductal Adenocarcinoma

Keywords

Neoadjuvant therapy; PEGPH20; Atezolizumab; Columbia; Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Change in the Number of CD8+ T Cells Within the Tumor

  The change in number of intratumoral CD8+ T-cells the at time of surgery between treatment arm(s) compared to the atezolizumab arm. The CD8+ T-cell count within the tumor with neoadjuvant atezolizumab vs atezolizumab + PEGPH20 at the time of surgery will be reported using means and standard deviations by group and will be compared using a twosample T-test. If the data are not normally distributed, non-parametric models such as the Wilcoxon Rank Sum test will be used. Moreover, the distribution of CD8+ T-cell count by treatment arm will be assessed using box plots, histograms, and q-q plots.

  At time of surgery (approximately 3 weeks)

Secondary Outcomes (4)

• 18-Month Survival Rate

  18 Months

• Overall Survival

  Up to 5 years

• R0 Resection Rate

  At time of surgery (approximately 3 weeks)

• Incidence of Treatment-Emergent Adverse Events

  Cycle 1 through 28 days after adjuvant chemotherapy period

Study Arms (2)

Atezolizumab

ACTIVE COMPARATOR

Atezolizumab 840mg IV every 2 weeks for 2 doses prior to surgery and 4 doses after surgery.

Drug: Atezolizumab

Atezolizumab in combination with PEGPH20

EXPERIMENTAL

Atezolizumab 840mg IV every 2 weeks for 2 doses prior to surgery and 4 doses after surgery in combination with PEGPH20 3ug/kg IV twice weekly for 3 weeks prior to surgery and once weekly for 3 weeks (of 28 day cycle) for two cycles after surgery.

Drug: Atezolizumab; Drug: PEGPH20

Interventions

Atezolizumab DRUG

840mg IV every 2 weeks for 2 doses prior to surgery and 4 doses after surgery.

Also known as: Tecentriq

Atezolizumab; Atezolizumab in combination with PEGPH20

PEGPH20 DRUG

PEGPH20 3ug/kg IV twice weekly for 3 weeks prior to surgery and once weekly for 3 weeks (of 28 day cycle) for two cycles after surgery.

Also known as: pegvorhyaluronidase alfa

Atezolizumab in combination with PEGPH20

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological or pathological confirmation of pancreatic adenocarcinoma Cytologic or histologic proof of PDA needs to be verified by the treating institution pathologist either from the initial diagnostic biopsy, or from the required pre treatment biopsy and prior to initiation of any study-related therapy
• Extent of disease. Stage 1 or 2 PDA and patient deemed a surgical candidate by the PI in consultation with the designated site radiologist and surgeon at the treating institution
• No prior surgical, systemic or radiotherapy for PDA.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Minimum age of at least 18 years.
• Adequate hematological and end-organ function, defined by laboratory test results, obtained within 14 days prior to initiation of study treatment:
• Tumor accessible for fresh biopsy
• Women of child-bearing potential must have a negative serum pregnancy test at screening and must agree to use two forms of effective contraception from the time of the negative pregnancy test and for a minimum of 5 months after the last dose of study drug. Women will be considered not of child-bearing potential if amenorrheic at least for one year or have undergone surgical sterilization.
• Fertile men must agree to use an effective method of birth control during the study and for up to 5 months after the last dose of study drug.
• Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements.
• Able to comply with the study protocol, in the investigator's judgment.

You may not qualify if:

• Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, including but not limited to anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies.
• Patients who are receiving any other investigational agents concurrently.
• Concomitant treatment with other anti-neoplastic agents (hormonal therapy acceptable).
• Uncontrolled pleural effusion, pericardial effusion, or ascites.
• Patient receiving therapeutic doses of anticoagulation.
• Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy.
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study.
• Patients with controlled Type 1 diabetes mellitus who are on a stable insulin regimen are eligible for the study.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Rash must cover \< 10% of body surface area.
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids.
• No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
• History of idiopathic pulmonary fibrosis, interstitial lung disease, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
• History of radiation pneumonitis in the radiation field (fibrosis) is permitted

Sponsors & Collaborators

• Gulam Manji: lead
• Genentech, Inc.: collaborator
• Halozyme Therapeutics: collaborator

Study Sites (1)

Columbia University

New York, New York, 10032, United States

Location

MeSH Terms

Interventions

atezolizumab; PEGPH20

Results Point of Contact

• Title: Gulam Manji, MD, PhD
• Organization: Columbia University

gam2140@columbia.edu

212-305-0592

Study Officials

• Gulam Manji, MD, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine at Columbia University Medical Center

Model Details: Randomized phase 2 trial for a total of 20 patients per cohort

Study Record Dates

• First Submitted: June 6, 2019
• First Posted: June 7, 2019
• Study Start: November 1, 2019
• Primary Completion: November 3, 2019
• Study Completion: November 3, 2019
• Last Updated: December 23, 2020
• Results First Posted: December 23, 2020

Record last verified: 2020-12

Locations

US (1)