Targeted Pathway Inhibition in Patients With Pancreatic Cancer

NCT04005690 | Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY00019211NCI-2019-01265
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This early phase I trial aims to determine how cobimetinib, olaparib, onvansertib, azenosertib, AZD5305 or tremelimumab works in patients with pancreatic cancer. Validation of cobimetinib, olaparib, onvansertib azenosertib, AZD5305 and tremelimumab molecular targets will be explored by comparing pre-treatment biopsies with post-treatment specimens. This knowledge will help design future biomarker driven trials to determine whether giving cobimetinib, or olaparib, or onvansertib or azenosertib, or AZD5305, or tremelimumab will work better than standard treatments in patients with pancreatic cancer.

Conditions

Locally Advanced Pancreatic Ductal Adenocarcinoma; Metastatic Pancreatic Ductal Adenocarcinoma; Stage II Pancreatic Cancer AJCC v8; Stage III Pancreatic Cancer AJCC v8; Stage IV Pancreatic Cancer AJCC v8; Unresectable Pancreatic Ductal Adenocarcinoma; Borderline Resectable Pancreatic Ductal Adenocarcinoma; Resectable Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Proportion of all pharmacodynamic feasibility-evaluable participants within a study arm that have a measurable change in post-treatment tumor biology from baseline

  Will be estimated with a 95% confidence interval (CI).

  Changes in tumor biology from baseline (i.e., Day 0) and on-treatment biopsy (i.e., 10 days from start of study intervention)

Secondary Outcomes (1)

• Incidence of >= grade 3 toxicities for each assigned window treatment (as described in sub-protocol)

  Up to 30 days

Study Arms (6)

Arm Olaparib

EXPERIMENTAL

Patients receive olaparib PO BID on days 1-10 in the absence of disease progression or unacceptable toxicity. Within 12-24 hours, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease. (Arm Closed as of 8/12/2024)

Drug: Olaparib

Arm Cobimetinib

EXPERIMENTAL

Patients receive cobimetinib PO QD on days 1-10 in the absence of disease progression or unacceptable toxicity. Within 12-24 hours, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease. (Arm Closed as of 8/12/2024)

Drug: Cobimetinib

Arm Onvansertib

EXPERIMENTAL

Patients receive onvansertib PO QD on days 1-10 in the absence of disease progression or unacceptable toxicity. Within 12-24 hours, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease. (Arm Closed as of 8/12/2024)

Drug: Onvansertib

Arm Azenosertib

EXPERIMENTAL

Patients receive azenosertib PO QD on days 1-10 in the absence of disease progression or unacceptable toxicity. Within 12-24 hours, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease.

Drug: Azenosertib

Arm AZD5305

EXPERIMENTAL

Patients receive AZD5305 PO QD on days 1-10 in the absence of disease progression or unacceptable toxicity. Within 12-24 hours, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease.

Drug: Saruparib

Arm Tremelimumab

EXPERIMENTAL

Patients receive tremelimumab IV over 60 minutes one-time. Within 12-24 hours of cycle completion, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease.

Biological: Tremelimumab

Interventions

Cobimetinib DRUG

Given PO

Also known as: Cotellic, GDC-0973, MEK Inhibitor GDC-0973, XL518

Arm Cobimetinib

Olaparib DRUG

Given PO

Also known as: AZD 2281, AZD-2281, AZD2281, KU-0059436, Lynparza, PARP Inhibitor AZD2281

Arm Olaparib

Onvansertib DRUG

Given PO

Also known as: 'PLK1 Inhibitor PCM-075, NMS-1286937, PCM 075, PCM-075, PLK-1 Inhibitor PCM-075, Polo-like Kinase 1 Inhibitor NMS-1286937, Polo-like Kinase 1 Inhibitor PCM-075

Arm Onvansertib

Azenosertib DRUG

Given PO

Also known as: ZN-c3, KP-2638, C29H34N8O2

Arm Azenosertib

Saruparib DRUG

Given PO

Also known as: AZD5305, 2589531-76-8, AZD 5305, AZD-5305, PARP Inhibitor AZD5305

Arm AZD5305

Tremelimumab BIOLOGICAL

Given IV

Also known as: 745013-59-6, Anti-CTLA4 Human Monoclonal Antibody CP-675,206, CP 675, CP 675206, CP-675, CP-675,206, CP-675206, CP675, CP675206, Imjudo, Immunoglobulin G2, Anti-(Human CTLA-4 (Antigen)) (Human Monoclonal CP-675206 Clone 11.2.1 Heavy Chain) Disulfide with Human Monoclonal CP-675206 Clone 11.2.1 Light Chain, Dimer, ticilimumab, Tremelimumab-actl

Arm Tremelimumab

Eligibility Criteria

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

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document
• Age \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Clinically-confirmed diagnosis of resectable, borderline resectable, locally-advanced or metastatic adenocarcinoma of the pancreas.
• Patients with disease that is eligible for curative surgery may not be eligible for all study arms.
• Participants may be treatment naïve or have received prior therapy for the treatment of their pancreatic ductal adenocarcinoma (PDAC). A minimum washout period of 10-days after completing the most recent line of therapy is required before a participant can initiate treatment with study agent(s)
• Based on available imaging, participant must have at least one disease lesion that can be biopsied in accordance with institutional standards
• Hemoglobin \>= 9.0 g/dL with no blood transfusion within 28 days of starting treatment (within 4 weeks prior to initiating window treatment). Note: laboratory tests performed after initial screening (but still within the screening window) will be evaluated by the investigator; should any of these values fall outside eligibility parameters, the patient may still be eligible per investigator discretion
• White blood cells (WBC) \> 3 x 10\^9/L (within 4 weeks prior to initiating window treatment). Note: laboratory tests performed after initial screening (but still within the screening window) will be evaluated by the investigator; should any of these values fall outside eligibility parameters, the patient may still be eligible per investigator discretion
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (\> 1500 per mm\^3) (within 4 weeks prior to initiating window treatment). Note: laboratory tests performed after initial screening (but still within the screening window) will be evaluated by the investigator; should any of these values fall outside eligibility parameters, the patient may still be eligible per investigator discretion.
• May be waived on a case-by-case basis for patient populations recognized to have normal baseline values below this level
• Platelet count \>= 100 x 10\^9/L (\> 100,000 per mm\^3) (within 4 weeks prior to initiating window treatment). Note: laboratory tests performed after initial screening (but still within the screening window) will be evaluated by the investigator; should any of these values fall outside eligibility parameters, the patient may still be eligible per investigator discretion
• Creatinine =\< 1.5 x upper limit of normal (ULN), OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 60 mL/min/1.73m\^2 for participants with creatinine levels \> 1.5 x institutional ULN (within 4 weeks prior to initiating window treatment). Note: laboratory tests performed after initial screening (but still within the screening window) will be evaluated by the investigator; should any of these values fall outside eligibility parameters, the patient may still be eligible per investigator discretion.
• Creatinine clearance should be calculated per institutional standard. For participants with a baseline calculated creatinine clearance below normal institutional laboratory values, a measured baseline creatinine clearance should be determined. Individuals with higher values felt to be consistent with inborn errors of metabolism will be considered on a case-by-case basis
• Serum bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (within 4 weeks prior to initiating window treatment). Note: laboratory tests performed after initial screening (but still within the screening window) will be evaluated by the investigator; should any of these values fall outside eligibility parameters, the patient may still be eligible per investigator discretion

You may not qualify if:

• Tumor not accessible for core biopsy
• Medical co-morbidities that are deemed to make risk of surgery unacceptably high as determined by institutional standards
• Recent major surgery within 4 weeks prior to starting study treatment. Minor surgery within 2 weeks of starting study treatment. Patients must be recovered from effects of surgery
• Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's wort) or moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil)
• Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil)
• Concomitant use of other anti-cancer therapy (chemotherapy, immunotherapy, hormonal therapy (hormone replacement therapy is acceptable), radiotherapy (except for palliative), biological therapy or other novel agent) or live virus and live bacterial vaccines while the patient is receiving study medication. Strong or moderate CYP3A inhibitors and inducers should not be taken with study treatment; however, if no other suitable alternative concomitant medication is available, dose reductions may be allowed under careful monitoring
• Known severe hypersensitivity to the study agent(s) (or equivalent agents, respectively), or any excipient of these medicinal products, or history of allergic reactions attributed to compounds of similar chemical or biologic composition to the study agent(s)
• Clinically significant cardiac disease or impaired cardiac function, including any of the following:
• Clinically significant and/or uncontrolled heart disease such as congestive heart failure (New York Heart Association grade \>= 2) uncontrolled hypertension, or clinically significant arrhythmia currently requiring medical treatment
• Corrected QT using Fridericia's formula (QTcF) \> 470 msec for females, or \> 450 msec for males, on screening electrocardiogram (ECG) or congenital long QT syndrome
• Acute myocardial infarction or unstable angina pectoris \< 6 months prior to screening
• Clinically significant cardiac disease or impaired cardiac function
• Female participant who is pregnant or lactating
• Participant is known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally
• Participant has active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment)

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• American Association for Cancer Research: collaborator
• Oregon Health and Science University: collaborator
• Genentech, Inc.: collaborator
• Cardiff Oncology: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

cobimetinib; olaparib; onvansertib; AZD5305; tremelimumab; Immunoglobulin G; Antigens; Disulfides

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Factors; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Study Officials

• Charles D Lopez

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 23, 2019
• First Posted: July 2, 2019
• Study Start: August 1, 2019
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): February 1, 2028
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

US (1)