Combination Therapy in Patients With Localized Pancreatic Ductal Adenocarcinoma
ConditionPancreatic Ductal Adenocarcinoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorGulam Manji
About this trial
The purpose of this study is to combine standard radiation therapy with drugs that encourages the body's immune system against cancer cells and simultaneously adding drugs which also target the pathway that the tumor uses to evade the immune system (CD73 and A2a/b). The study hopes that these drugs will work in concert with radiation therapy to kill cancer cells.
The specific goal of this study is to ensure that treatment with zimberelimab and stereotactic body radiation therapy (SBRT) alone or in combination with quemliclustat (a drug which blocks CD73), with or without etrumadenant (a drug which blocks the A2a/b) given before surgery is safe and if it can further increase the immune response against the tumor.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Histological or pathological confirmation of pancreatic adenocarcinoma Cytologic or histologic proof of pancreatic ductal adenocarcinoma (PDAC) needs to be verified by the treating institution pathologist. A pathological report from non-treating institutions is sufficient to consent and to initiate investigational therapy if tissue sample is unavailable for evaluation at time of consent or enrollment. However, in such a case, PDAC diagnosis should be confirmed by the treating institution pathologist at a later time.
Completed 8 cycles of neoadjuvant modified FOLFIRINOX. Omission of oxaliplatin due to adverse events may be allowed in cycles 5-8 with consultation with the principal investigator.
Patients with surgically resectable PDAC who are considered appropriate to undergo the applicable operation.
Eligible to undergo SBRT.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Stereotactic body radiotherapy (SBRT)
RadiationSBRT 40 gray (Gy) over 5 fractions
Zimberelimab
Drug240 mg intravenously (IV)
Quemliclustat
Drug100 mg IV
Etrumadenant
Drug150 mg orally
Modified FOLFIRINOX
Drug* Oxaliplatin 85 mg per square meter IV * Irinotecan 150 mg per square meter IV * Leucovorin 400 mg per square meter IV * Fluorouracil 2400 mg per square meter IV * Pegfilgrastim injector kit (6mg subcutaneous)
Treatment groups
60 Participants
are divided into 4 treatment groupsGroup A: Arm A: Safety run-inExperimental treatment 5 interventions
Group B: Arm B: SBRT with Zimberelimab (AB122) Alone (Control Arm)Active comparator 3 interventions
Group C: Arm C: SBRT, Zimberelimab with quemliclustat (AB680)Experimental treatment 4 interventions
Group D: Arm D: SBRT, Zimberelimab with AB680 and Etrumadenant (AB928)Experimental treatment 5 interventions
Trial outcomes
Primary outcomes
1
Change in the number of intratumoral CD8+ T-cells
The primary endpoint is change in the number of intratumoral CD8+ T-cells at time of surgery between treatment arm(s) compared to the SBRT + zimberelimab arm (Control Arm B). To obtain CD8+ T-cell count, simple immunohistochemistry (IHC) will be used to quantitate CD8+ T-cells. A designated gastrointestinal (GI) pathologist will review each hematoxylin and eosin (H\&E) stained serial section and IHC slide to oversee the process. Representative areas within the slide will be used for cell counts.
Time frame
PerioperativeSecondary outcomes
1
Resection rate
The proportion of patients undergoing surgical resection after randomization. Patients that do not undergo an explorative laparotomy at all or do undergo an explorative laparotomy but not a resection are considered a failure.
Time frame
Week 82
Microscopically Negative Margins (R0) resection rate
R0 resection rate: Defined as the percentage of eligible patients who underwent surgery with microscopically negative margins (R0). The resection is considered R0 if the inked margin is further than 1 mm distinct from any tumor cells. .
Time frame
Week 83
Pathologic Complete Response Rate
Pathologic complete response rates after R0 or R1 resection as per the Modified Ryan Scheme for Tumor Regression Score (no viable cancer cells). R0 defined as inked margin is further than 1 mm distinct from any tumor cells. R1 defined as macroscopically curative resection, but tumor cells are observed by microscopy at one or more edges of the resected specimen.
Time frame
Week 84
Recurrence free survival
Defined as investigator assessed survival without overt recurrent pancreatic cancer from the date of randomization. Any sign of recurrent or persistent disease, locoregional or distant, as well as death from any cause is considered an event for this endpoint. Recurrence of disease is defined as radiological evidence of recurrence that is confirmed by biopsy. However, if recurrence is suspected due to participant symptoms consistent with disease recurrence and rising tumor markers (that are not explained due to inflammation or biliary obstruction) may result in sooner scans. All efforts will be made to confirm recurrence by conducting a biopsy if considered safe. If a patient is unable to undergo biopsy to confirm recurrence, these cases will be discussed at the institutional multidisciplinary conference for consensus and discussed with the overall study principal investigator (PI) and the participant will be deemed to have clinical recurrence.
Time frame
18 monthsSponsors and contacts
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Source ClinicalTrials.gov