Clinical trial for Advanced Pancreatic Ductal Adenocarcinoma
Official title Testing the Combination of Anti-Cancer Drugs, Selumetinib and DS-8201a (Trastuzumab Deruxtecan), for Advanced Pancreatic Ductal Adenocarcinoma
ClinicalTrials.gov ID: NCT07619521
What this study is testing
What is Selumetinib?
Selumetinib is an investigational medicine, being studied as a potential treatment for advanced pancreatic ductal adenocarcinoma.
Also referred to as ARRY-142886, AZD 6244.
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 phase I/II trial tests the safety, side effects, best dose and how well giving selumetinib with trastuzumab deruxtecan (DS-8201a) works for the treatment of pancreatic ductal adenocarcinoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced), that cannot be removed by surgery (unresectable) or that has spread from where it first started (primary site) to other places in the body (metastatic). Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
- Phase 2: a mid-size study of how well it works
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
- Review of eligibility criteria by the study principal investigator (PI) is required prior to enrollment
- Patients must have histologically or cytologically confirmed adenocarcinoma of the pancreas
- Patients must have unresectable or metastatic disease with KRAS mutation per Next Generation Sequencing (NGS) tumor testing and HER2...
- Patients must have measurable disease that can fulfill Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
- Patients must have exposure to at least one line of systemic chemotherapy for metastatic or unresectable PDAC (for both escalation and phase II...
You likely can't join if
- Patients with prior MEK inhibitor, ERK inhibitor, or HER2-directed therapy treatment
- Patients who have had chemotherapy (including antibody drug therapy, retinoid therapy, hormonal therapy for cancer) within 3 weeks (2 weeks or five...
- Patients who have had immunotherapy including monoclonal antibody therapy within 4 weeks
- Patients who have a history of severe hypersensitivity reactions to other monoclonal antibodies
- Patients who have had a major surgery within 4 weeks
- Patients with a history of allogeneic organ or stem cell transplant
See the full eligibility criteria
Who can join
- Review of eligibility criteria by the study principal investigator (PI) is required prior to enrollment
- Patients must have histologically or cytologically confirmed adenocarcinoma of the pancreas
- Patients must have unresectable or metastatic disease with KRAS mutation per Next Generation Sequencing (NGS) tumor testing and HER2 immunohistochemistry (IHC) positivity (2+ or above for dose escalation and per...
- Patients must have measurable disease that can fulfill Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
- Patients must have exposure to at least one line of systemic chemotherapy for metastatic or unresectable PDAC (for both escalation and phase II cohorts) or a documented patient decision to forego therapy that has an...
- Patients who have received prior topoisomerase inhibitors including irinotecan and nanoliposomal irinotecan will be eligible for this study
- Only 1 prior line of therapy for metastatic or unresectable PDAC will be allowed for patients in the phase II cohort.
- Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of selumetinib (AZD6244 hydrogen sulfate) in combination with DS-8201a (trastuzumab deruxtecan) in patients \< 18 years of age...
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 70%). Regardless of performance status, enrollment should be based on the judgment of the treating physician that the patient will be able to...
- Hemoglobin ≥ 9 g/dL (within 14 days of enrollment)
- No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment
- Leukocytes ≥ 3,000/mcL (within 14 days of enrollment)
- Absolute neutrophil count ≥ 1,500/mcL (within 14 days of enrollment)
- No administration of granulocyte colony-stimulating factor (G-CSF) is allowed within 1 week prior to screening assessment
- Platelets ≥ 100,000/mcL (within 14 days of enrollment)
- Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN), (\< 3 × ULN in the presence of documented Gilbert's syndrome or liver metastases at baseline) (within 14 days of enrollment)
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) \< 5 × ULN in participants with liver metastases (within 14...
- Serum albumin ≥ 2.5 g/dL (within 14 days of enrollment)
- International Normalized Ratio (INR)/Prothrombin Time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (within 14 days of enrollment)
- Creatine phosphokinase (CPK) ≤ 2.5 × ULN (within 14 days of enrollment)
- Glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2 (within 14 days of enrollment)
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- Patients with treated brain metastases are eligible if follow-up brain imaging, performed at least 6 months after central nervous system (CNS)-directed therapy, shows no evidence of progression
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or how well it works assessment of the investigational regimen are eligible for...
- Patients with a known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must undergo a clinical risk assessment of cardiac function using the New York Heart Association...
- Patients must have a baseline left ventricular ejection fraction (LVEF) ≥ 50% as measured by echocardiogram (ECHO) or mutilated acquisition scan (MUGA) scan within 28 days before randomization/enrollment
- Patients must be willing to undergo baseline ophthalmic evaluation, including visual acuity and slit-lamp examination
- The effects of selumetinib (AZD6244 hydrogen sulfate) and DS-8201a (trastuzumab deruxtecan) on the developing human fetus are unknown.
- Women of non-child-bearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy
- Male people must not freeze or donate sperm starting at screening and throughout the study period, and at least 4 months after the final study drug administration.
- Female people must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the final study drug administration
- Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
What rules you out
- Patients with prior MEK inhibitor, ERK inhibitor, or HER2-directed therapy treatment
- Patients who have had chemotherapy (including antibody drug therapy, retinoid therapy, hormonal therapy for cancer) within 3 weeks (2 weeks or five half-lives, whichever is longer for small-molecule targeted agents such...
- Patients who have had immunotherapy including monoclonal antibody therapy within 4 weeks
- Patients who have a history of severe hypersensitivity reactions to other monoclonal antibodies
- Patients who have had a major surgery within 4 weeks
- Patients with a history of allogeneic organ or stem cell transplant
- Patients who are receiving any other investigational agents or received any other investigational agents within the past 21 days prior to protocol treatment initiation
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib (ADZ6244 hydrogen sulfate) or DS-8201a (trastuzumab deruxtecan)
- Current use or anticipated need for alternative, holistic, naturopathic, or botanical formulations used for the purpose of cancer treatment
- Patients with prior use of immunosuppressive medication within 14 days prior to first study dose, except for intranasal and inhaled corticosteroids or systemic corticosteroids at doses less than 10 mg/day of prednisone...
- Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
- Patients with a corrected QT interval (QTc) prolongation to \> 470 ms (females) or \> 450 ms (males) based on average of the screening triplicate 12-lead electrocardiogram (ECG)
- Patients with a history of (non-infectious) interstitial lung disease (ILD) that required steroids, presence of ILD that is symptomatic or may interfere with the detection or management of suspected treatment-related...
- Patients with lung-specific, intercurrent, clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within three months prior to study enrollment, severe...
- Patients with gastrointestinal conditions which could impair absorption of selumetinib (AZD6244 hydrogen sulfate) or inability to ingest selumetinib (AZD6244 hydrogen sulfate)
- Patients with a history of significant retinal pathology (including but not limited to, retinal vein occlusion, retinal detachment, or macular degeneration) or clinically significant ophthalmic abnormalities that may...
- Active ocular disease requiring systemic therapy or current use of contact lenses that may interfere with ophthalmic evaluations
- Based on pre-clinical and clinical data, DS-8201a (trastuzumab deruxtecan) and selumetinib (AZD6244 hydrogen sulfate) are associated with ocular toxicity.
- Patients who have had chest radiation therapy within 4 weeks (2 weeks for palliative stereotactic body radiation therapy).
- Patients with spinal cord compression, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms
- Patients with an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
- Patients that have received a live vaccine within 30 days prior to the first dose of study drug will be excluded.
- Patients with unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia or peripheral neuropathy) not yet resolved to grade ≤ 1 or baseline.
- Patients with ongoing muscle disorders or elevated baseline creatine phosphokinase (CPK) levels suggestive of rhabdomyolysis or myopathy
- Patients currently using high-dose vitamin E supplements exceeding the recommended daily intake (≥ 400 IU/day) or concurrent use of anticoagulants/antiplatelets that may increase bleeding risk, unless clinically...
- Pregnant women are excluded from this study because selumetinib (AZD6244 hydrogen sulfate) is a MEK inhibitor agent with the potential for teratogenic or abortifacient effects.
- Patients who have received prior systemic anticancer therapy, investigational agents, or radiotherapy without completion of an adequate washout period prior to study treatment initiation defined as at least 14 days or...
The study team makes the final eligibility decision.
Where it is enrolling
- Pittsburgh, Pennsylvania, 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, but 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?
This study is enrolling now at Pittsburgh, Pennsylvania, United States. Enter your location above to see the nearest enrolling site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool that is independent of the study sponsor. Details come from ClinicalTrials.gov. The study team decides eligibility, and your own doctor gives medical advice.