Locally Advanced Pancreatic Ductal AdenocarcinomaEarly Phase 1NCT04005690
Targeted Pathway Inhibition in Patients With Pancreatic Cancer
A Early Phase 1 study testing Cobimetinib, Olaparib and Onvansertib in people with Locally Advanced Pancreatic Ductal Adenocarcinoma and Metastatic Pancreatic Ductal Adenocarcinoma, run by OHSU Knight Cancer Institute at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced Pancreatic Ductal Adenocarcinoma, Metastatic Pancreatic Ductal Adenocarcinoma, Stage II Pancreatic Cancer AJCC v8
- What is being tested?
- Cobimetinib, Olaparib and Onvansertib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2019to 1 Feb 2028
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x 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
- Participants must be willing to undergo mandatory on-study tumor biopsies
- Participant is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
- Participant must be able to swallow tablets or capsules. A participant with any gastrointestinal disease that would impair ability to swallow, retain, or absorb drug is not eligible
- Participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Participants must agree to use an adequate method of contraception starting with the first dose of study therapy and for the required length of time ascribed to the assigned study drug assignment
- No other prior invasive malignancy is allowed except for the following: adequately treated basal (or squamous cell) skin cancer, in situ breast or cervical cancer, any malignancy treated with a curative intent without evidence of disease recurrence for at least 6 months
- Individuals must not have known active hepatitis B virus (HBV). Those who have completed curative therapy for hepatitis C virus (HCV) are eligible. HCV infection permitted but patient must be Child's Pugh A. Patients with known human immunodeficiency virus (HIV) infection are eligible if they meet all of the following 3 criteria:
- CD4 counts >= 350 mm^3
- Serum HIV viral load of < 25,000 IU/ml and
- Treated on a stable antiretroviral regimen
- Note: HIV testing is not required at screening, unless if required by local regulations, where the testing will be done by local laboratory
- AZENOSERTIB SPECIFIC CRITERIA: Those with prior treatment with a WEE1 inhibitor are not eligible
- AZENOSERTIB SPECIFIC CRITERIA: Patients are not eligible if any of the following treatment interventions have occurred within the specified time frame(s) prior to starting study intervention:
- Major surgery within 28 days (the surgical incision should be fully healed prior to study drug administration)
- Radiation therapy within 21 days; however, if the radiation portal covered ≤ 5% of the bone marrow reserve, the subject is eligible irrespective of the end date of radiotherapy
- Autologous or allogeneic stem cell transplant within 3 months
- Current use of an investigational agent that is not expected to be cleared by the first dosing of study drug or that has demonstrated to have prolonged side effects
- Prescription, non-prescription drugs or food known as moderate to strong inducers of CYP3A within 2 weeks
- AZENOSERTIB SPECIFIC CRITERIA: Patients are not eligible if there is a serious illness or medical condition(s) including, but not limited to, the following:
- Symptomatic brain metastases
- Leptomeningeal disease that requires or is anticipated to require immediate treatment.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the subject inappropriate for entry into this study
- Significant gastrointestinal abnormalities, including an inability to take oral medication, requirement for IV alimentation, active peptic ulcer, chronic diarrhea or vomiting considered to be clinically significant in the judgment of the Investigator, or prior surgical procedures affecting absorption
- Active or uncontrolled infection. Subjects with an infection receiving treatment (antibiotic, antifungal or antiviral treatment) may be entered into the study but must be afebrile and hemodynamically stable for ≥ 72 hours
- AZENOSERTIB SPECIFIC CRITERIA: 12-lead ECG demonstrating a corrected QT interval using Fridericia's formula (QTcF) of >480 ms, except for subjects with atrioventricular pacemakers or other conditions (e.g., right bundle branch block) that render the QT measurement invalid
- AZENOSERTIB SPECIFIC CRITERIA: History or current evidence of congenital or family history of long QT syndrome or Torsade de Pointes
- AZENOSERTIB SPECIFIC CRITERIA: Patients are not eligible in cases of unresolved toxicity of grade > 1 attributed to any prior therapies (excluding grade 2 neuropathy, alopecia or skin pigmentation)
- AZENOSERTIB SPECIFIC CRITERIA: Patients are not eligible if there is known hypersensitivity to any drugs similar to ZN-c3 in class
- AZENOSERTIB SPECIFIC CRITERIA: Individuals that are pregnant or breast-feeding are not eligible
- AZENOSERTIB SPECIFIC CRITERIA: Participants must agree to use an adequate method of contraception as follows:
- Participants of childbearing potential agree to use adequate methods of contraception for the duration of study participation.
- Sperm-producing participants must agree to refrain from sperm donation during the study and for 30 days after the last dose of study drug
- AZENOSERTIB SPECIFIC CRITERIA: Participant requiring any medications that can lead to significant QT prolongation are not eligible
- AZENOSERTIB SPECIFIC CRITERIA: Participant requires administration of strong and moderate CYP3A4 inhibitors and inducers as well as strong and moderate P-glycoprotein (P-gp) inhibitors are not eligible
- AZENOSERTIB SPECIFIC CRITERIA: Due to potential CYP3A4 interaction with the study medication, participants are asked to refrain from consumption of seville oranges, grapefruit or grapefruit juice, ppomelos, exotic citrus fruits, grapefruit hybrids, or fruit juices) from 7 days prior to the initiating study agent and during the entire study. NOTE: Orange juice is permitted
- AZD5305 SPECIFIC CRITERIA: Participants must agree to use an adequate method of contraception as follows:
- Participants of childbearing potential must agree to use adequate methods of contraception starting with the first dose of study therapy through at least 6 months after the last dose of study therapy
- Sperm-producing participants must use a condom during treatment and for 6 months after the last dose of AZD5305 when having sexual intercourse with an individual that is pregnant or of childbearing potential. Individuals that are partners of sperm-producing participants should also use a highly effective form of contraception if they are of childbearing potential
- TREMELIMUMAB SPECIFIC CRITERIA: Participants of childbearing potential must agree to use adequate methods of contraception starting with the first dose of study therapy through at least 3 months after the last dose of study therapy
Who cannot join
- 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
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- 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)
- Psychiatric illness/social situations that would limit compliance with study requirements
- Participants with a history of hypersensitivity reactions to study agents or their excipients
- Participant is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through at least 120 days after the last dose of trial treatment
- AZD5305 SPECIFIC CRITERIA: Known allergy or hypersensitivity to AZD5305 or any of its excipients
- AZD5305 SPECIFIC CRITERIA: Patients with myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML
- AZD5305 SPECIFIC CRITERIA: Cardiovascular disease, QTc > 450 ms, or any factors that increase the risk of QTc prolongation or risk of arrhythmic events
- AZD5305 SPECIFIC CRITERIA: History of persisting (> 2 weeks) severe pancytopenia due to any cause (ANC < 0.5 x 10^9/L or platelets < 50 x 10^9/L)
- TREMELIMUMAB SPECIFIC CRITERIA: Medical co-morbidities that are deemed to make risk of surgery unacceptably high as determined by institutional standards
- TREMELIMUMAB SPECIFIC CRITERIA: Participants have received prior immunotherapy for the treatment of their PDAC
- TREMELIMUMAB SPECIFIC CRITERIA: Any unresolved toxicity Common Terminology Criteria for Adverse Events (CTCAE) > grade 2 from prior neoadjuvant therapy
- TREMELIMUMAB SPECIFIC CRITERIA: History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis, interstitial lung disease (ILD), pleural effusion, or pulmonary fibrosis diagnosed in the past 6 months prior to randomization
- TREMELIMUMAB SPECIFIC CRITERIA: Active or prior documented autoimmune or inflammatory disorders
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
OHSU Knight Cancer Institute
Portland, Oregon, 97239
Charles D. Lopez, 503-494-8534, lopezc@ohsu.edu
Charles D. Lopez
About this study
Official title: A Window of Opportunity Strategy for Targeted Pathway Inhibition in Patients With Pancreatic Ductal Adenocarcinoma
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.
Read the detailed description
PRIMARY OBJECTIVE:
- Independently assess the pharmacodynamic (PD) feasibility of detecting a measurable change in tumor biology at post-treatment from baseline (i.e., before the study treatment window) for all feasibility-evaluable participants in each study arm.
SECONDARY OBJECTIVE:
- Assess preliminary safety and tolerability of the proposed study agent(s) in each study arm.
EXPLORATORY OBJECTIVES:
- Identify predictive biomarkers of sensitivity to assigned study agent(s).
II. Identify emerging mechanism(s) of resistance to assigned study agent(s).
III. Determine cellular and molecular changes in pancreatic tumor cells exposed to assigned study agent(s).
IV. Identify tumor markers suggestive of combinatorial therapy that could overcome resistance to therapy.
OUTLINE: Patients are assigned to 1 of 6 arms.
ARM Olaparib: Patients receive olaparib orally (PO) twice daily (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)
ARM Cobimetinib: Patients receive cobimetinib PO once daily (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)
ARM Onvansertib: 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)
ARM Azenosertib: 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.
ARM AZD5305: Patients receive AZD5305 (saruparib) 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 Tremelimumab: Patients receive tremelimumab intravenously (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.
After completion of study treatment, patients are followed up for 12 months.
- 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
- Being tested
- Cobimetinib, Olaparib, Onvansertib, Azenosertib, Saruparib
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CobimetinibDrug
Also called Cotellic, GDC-0973, MEK Inhibitor GDC-0973, XL518
Given PO
OlaparibDrug
Also called AZD 2281, AZD-2281, AZD2281, KU-0059436
Given PO
OnvansertibDrug
Also called 'PLK1 Inhibitor PCM-075, NMS-1286937, PCM 075, PCM-075
Given PO
AzenosertibDrug
Also called ZN-c3, KP-2638, C29H34N8O2
Given PO
SaruparibDrug
Also called AZD5305, 2589531-76-8, AZD 5305, AZD-5305
Given PO
TremelimumabBiological
Also called 745013-59-6, Anti-CTLA4 Human Monoclonal Antibody CP-675,206, CP 675, CP 675206
Given IV
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: 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) Receives: 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. Receives: 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. Receives: 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. Receives: Biological: Tremelimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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)
Assessed per Common Terminology Criteria for Adverse Events version 5.0. The 95% CI will be reported with the point estimate of toxicity rate. All grade 3+ acute toxicities will also be summarized with its grade.
Measured: Up to 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2019
- Study start1 Aug 2019
- Primary completion1 Jun 2027 (estimated)
- Study completion1 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Pancreatic Ductal AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by OHSU Knight Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- OHSU Knight Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- American Association for Cancer Research, Oregon Health and Science University, Genentech, Inc., Cardiff Oncology
- Responsible party
- Principal investigator, Charles D Lopez, OHSU Knight Cancer Institute
- Investigators
- Charles D Lopez, Principal investigator, OHSU Knight Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04005690
- Sponsor's protocol ID
- STUDY00019211
- Other IDs
- NCI-2019-01265, STUDY00019211
- Status last verified
- Sep 2026
- First submitted
- 23 May 2019
- Last updated
- 4 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Window of Opportunity Strategy for Targeted Pathway Inhibition in Patients With Pancreatic Ductal Adenocarcinoma
- ClinicalTrials.gov ID
- NCT04005690
- Acronym / sponsor ID
- STUDY00019211
- 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
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- OHSU Knight Cancer InstituteUniversity, hospital or other
- Collaborators
- American Association for Cancer Research, Oregon Health and Science University, Genentech, Inc., Cardiff Oncology
- Study start
- 1 Aug 2019 (actual)
- Primary completion
- 1 Jun 2027 (estimated)
- Study completion
- 1 Feb 2028 (estimated)
- First posted
- 2 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVE:
- Independently assess the pharmacodynamic (PD) feasibility of detecting a measurable change in tumor biology at post-treatment from baseline (i.e., before the study treatment window) for all feasibility-evaluable participants in each study arm.
SECONDARY OBJECTIVE:
- Assess preliminary safety and tolerability of the proposed study agent(s) in each study arm.
EXPLORATORY OBJECTIVES:
- Identify predictive biomarkers of sensitivity to assigned study agent(s).
II. Identify emerging mechanism(s) of resistance to assigned study agent(s).
III. Determine cellular and molecular changes in pancreatic tumor cells exposed to assigned study agent(s).
IV. Identify tumor markers suggestive of combinatorial therapy that could overcome resistance to therapy.
OUTLINE: Patients are assigned to 1 of 6 arms.
ARM Olaparib: Patients receive olaparib orally (PO) twice daily (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)
ARM Cobimetinib: Patients receive cobimetinib PO once daily (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)
ARM Onvansertib: 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)
ARM Azenosertib: 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.
ARM AZD5305: Patients receive AZD5305 (saruparib) 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 Tremelimumab: Patients receive tremelimumab intravenously (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.
After completion of study treatment, patients are followed up for 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Arm Olaparib | Experimental | Drug: OlaparibPatients 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) |
| Arm Cobimetinib | Experimental | Drug: CobimetinibPatients 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) |
| Arm Onvansertib | Experimental | Drug: OnvansertibPatients 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) |
| Arm Azenosertib | Experimental | Drug: AzenosertibPatients 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. |
| Arm AZD5305 | Experimental | Drug: SaruparibPatients 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. |
| Arm Tremelimumab | Experimental | Biological: TremelimumabPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (55 listed)
- 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.
- Based on available imaging, participant must have at least one disease lesion that can be biopsied in accordance with institutional standards
Key exclusion criteria (27 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CobimetinibAlso: Cotellic, GDC-0973, MEK Inhibitor GDC-0973, XL518Given PO | Drug | Arm Cobimetinib |
| OlaparibAlso: AZD 2281, AZD-2281, AZD2281, KU-0059436Given PO | Drug | Arm Olaparib |
| OnvansertibAlso: 'PLK1 Inhibitor PCM-075, NMS-1286937, PCM 075, PCM-075Given PO | Drug | Arm Onvansertib |
| AzenosertibAlso: ZN-c3, KP-2638, C29H34N8O2Given PO | Drug | Arm Azenosertib |
| SaruparibAlso: AZD5305, 2589531-76-8, AZD 5305, AZD-5305Given PO | Drug | Arm AZD5305 |
| TremelimumabAlso: 745013-59-6, Anti-CTLA4 Human Monoclonal Antibody CP-675,206, CP 675, CP 675206Given IV | Biological | Arm Tremelimumab |
Primary outcome
Proportion of all pharmacodynamic feasibility-evaluable participants within a study arm that have a measurable change in post-treatment tumor biology from baseline
Time frame: Changes in tumor biology from baseline (i.e., Day 0) and on-treatment biopsy (i.e., 10 days from start of study intervention)
Will be estimated with a 95% confidence interval (CI).
1 secondary outcome
Incidence of >= grade 3 toxicities for each assigned window treatment (as described in sub-protocol)
Time frame: Up to 30 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Charles D Lopez principal investigator
OHSU Knight Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Cobimetinib, Olaparib and Onvansertib in people with Locally Advanced Pancreatic Ductal Adenocarcinoma and Metastatic Pancreatic Ductal Adenocarcinoma, run by OHSU Knight Cancer Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 55 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of all pharmacodynamic feasibility-evaluable participants within a study arm that have a measurable change in post-treatment tumor biology from baseline (time frame: Changes in tumor biology from baseline (i.e., Day 0) and on-treatment biopsy (i.e., 10 days from start of study intervention)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2026.