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New treatment option for Locally Advanced Pancreatic Ductal Adenocarcinoma
Official title Targeted Pathway Inhibition in Patients With Pancreatic Cancer
ClinicalTrials.gov ID: NCT04005690
What this study is testing
What is Cobimetinib?
Cobimetinib is an investigational medicine, given as an once-daily infusion into a vein, being studied as a potential treatment for locally advanced pancreatic ductal adenocarcinoma.
Also referred to as Cotellic, GDC-0973.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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.
- Phase 1: an early, usually small safety study
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join 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.
You likely can't join 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...
- Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St...
- Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or...
- Concomitant use of other anti-cancer therapy (chemotherapy, immunotherapy, hormonal therapy (hormone replacement therapy is acceptable), radiotherapy...
See the full eligibility criteria
Who can 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...
- 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...
- 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...
- 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...
- 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...
- Creatinine =\ = 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...
- 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...
- 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)...
- 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...
- 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...
- 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...
- 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...
- 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...
- 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...
- Active or uncontrolled infection. people 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 people with atrioventricular pacemakers or other conditions (e.g., right bundle...
- 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...
- 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...
- 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...
What rules you out
- 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...
- Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir)...
- 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...
- 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...
- 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...
- 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...
- 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...
- 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)...
- TREMELIMUMAB SPECIFIC CRITERIA: Active or prior documented autoimmune or inflammatory disorders
The study team makes the final eligibility decision.
Where it's taking place
- Portland, Oregon, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Portland, Oregon, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.