- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05034627
Calaspargase Pegol-Mnkl and Cobimetinib for the Treatment of Locally Advanced or Metastatic Pancreatic Cancer
A Phase I, Open-Label, Dose Finding Study of Calaspargase Pegol-Mnkl in Combination With Cobimetinib in Locally-Advanced or Metastatic Pancreatic Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVE:
I. To determine the maximum tolerated dose (MTD) of calaspargase pegol-mknl in combination with cobimetinib.
SECONDARY OBJECTIVES:
I. To assess the safety of calaspargase pegol-mknl in combination with cobimetinib.
II. To assess preliminary response to treatment with calaspargase pegol-mknl and cobimetinib.
III. To monitor levels of plasma asparaginase.
EXPLORATORY OBJECTIVE:
I. To evaluate therapy induced changes in the tumor and tumor ecosystem.
OUTLINE: This is a dose-escalation study.
Patients receive calaspargase pegol-mknl intravenously (IV) over 1 hour on day 1 and cobimetinib orally (PO) once daily (QD) on days 1-14. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a biopsy 14 days prior to starting therapy and on day 14 of cycle 2.
After completion of study intervention, patients are followed up at 3 and 6 months.
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Oregon
-
Portland, Oregon, United States, 97239
- Recruiting
- OHSU Knight Cancer Institute
-
Contact:
- Charles D. Lopez
- Phone Number: 503-494-8321
- Email: lopezc@ohsu.edu
-
Principal Investigator:
- Charles D. Lopez
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Participant must provide written informed consent before any study-specific procedures or interventions are performed
- Participants are >= 18 years old at the time of informed consent. Both men and women of all races and ethnic groups will be included
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Histologically or cytologically-proven adenocarcinoma of the exocrine pancreas with locally advanced or metastatic disease
- Must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
- Must have at least one disease lesion that is amenable to biopsy procedures performed per institutional standards
- Must have progressed on, been intolerant to, or refused systemic therapy that is consistent with institutional standards (e.g., Gemcitabine-based, or fluorouracil, irinotecan, leucovorin and oxaliplatin [FOLFORINOX])
Must not have received any systemic therapy or other investigational agents within 30 days or 5 half-lives (whichever is longer) from first dose of study therapy
- This requirement is waived for patients receiving cobimetinib or other investigational agent(s) as part of participation in NCT04005690, provided that all prior drug-related toxicities have resolved to Grade ≤ 1 prior to initiating study intervention
- Hemoglobin: >= 9.0 g/dL with no blood transfusion within 14 days of starting treatment
- White blood cells (WBC): > 3 x 10^9/L
- Absolute neutrophil count (ANC): >= 1.5 x 10^9/L (> 1500 per mm^3)
- Platelet count: >= 100 x 10^9/L (> 100,000 per mm^3)
- Creatinine =< 1.5 x upper limit of normal (ULN), or measured or calculated creatinine clearance >= 60 mL/min/1.73 m^2 for participants with creatinine levels > 1 x institutional (ULN)
- Serum bilirubin: =< 1.5 x institutional ULN
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT): =< 2.5 x ULN
- Participants of childbearing potential (POCBP) must agree to abstain from sexual intercourse or use effective non-hormonal methods of contraception starting with the first dose of study therapy through 90 days after the last dose of study therapy (because calaspargase pegol can render hormonal contraceptives ineffective)
- POCBP may participate provided they have a negative serum pregnancy test at screening and a negative serum OR urine pregnancy test within 7 days of starting treatment
Exclusion Criteria:
- 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 receiving study medication
- Prior treatment with an L-asparaginase therapy
- Known severe hypersensitivity to calaspargase pegol-mknl (or equivalent) or to cobimetinib (or equivalent), or to any excipient of these medicinal products, or history of allergic reactions attributed to compounds of similar chemical or biologic composition to calaspargase pego-mknl or cobimetinib
- Use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir), known strong CYP3A inducers (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil) within 7 days of prior to initiating study treatment or on going requirement for these medications
- Uncontrolled serious thrombosis
Uncontrolled severe or symptomatic coagulopathy; exclude if:
- Prothrombin time (PT) >= 1.5 x ULN, or
- International normalized ratio (INR) >= 1.5 x ULN, or
- Fibrinogen =< 0.66 x LLN
Known history of chronic pancreatitis or recurrent acute pancreatitis, or at time of screening evidence of acute pancreatitis, defined by at least two of the following:
- Clinical symptoms of upper abdominal pain
- Serum amylase or lipase that is >= 3 x ULN
- Imaging evidence (computed tomography [CT], magnetic resonance imaging [MRI], ultrasonography)
Significant cardiac disease within 6 months prior to start of study treatment, including any of the following:
- New York Heart Association class III or IV,
- Congestive heart failure, acute coronary syndrome, and/or stroke, or
- Left ventricular ejection fraction (LVEF) < 40% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan obtained within 28 days prior to start of study treatment
Known risk factors for ocular toxicity, consisting of any of the following:
- History of serous retinopathy
- History of retinal vein occlusion (RVO)
- Evidence of ongoing serous retinopathy or RVO at screening
- Uncontrolled hypertension, or hypertension that cannot otherwise be clinically managed before initiating study therapy
- 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)
- Participant has corrected QT (QTc) interval (i.e., Fridericia's correction [QTcF]) >= 450 ms or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) at screening
- Psychiatric illness/social situations that would limit compliance with study requirements
- Any concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, etc.)
- 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 90 days after the last dose of trial treatment
- Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (calaspargase pegol-mknl, cobimetinib)
Patients receive calaspargase pegol-mknl IV over 1 hour on day 1 and cobimetinib PO QD on days 1-14.
Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
|
Undergo biopsy
Other Names:
Given IV
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of dose-limiting toxicities (DLTs)
Time Frame: Up to cycle 2 day 21 (1 cycle = 21 days)
|
Defined as any treatment-related grade >= 3 non-hematological or hematological adverse events.
The incidence of DLT at each dose level will be summarized using the proportion and exact binomial confidence interval.
Dose-limiting toxicities will specifically be reported for the DLT evaluation period using the maximum tolerated dose (MTD)-evaluable population.
The MTD will be identified using isotonic regression.
|
Up to cycle 2 day 21 (1 cycle = 21 days)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of treatment-emergent adverse events (AEs) and serious AEs
Time Frame: Up to 30 days after last dose of study intervention
|
Evaluated by Common Terminology Criteria for Adverse Events version 5.0.
|
Up to 30 days after last dose of study intervention
|
Objective response rate (ORR)
Time Frame: Up to 6 months after initiating study intervention
|
Evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Overall response will be summarized descriptively.
ORR will be estimated with 95% confidence interval.
The confidence interval will be calculated based on the exact method for binomial distributions.
|
Up to 6 months after initiating study intervention
|
Disease control rate (DCR)
Time Frame: Up to 6 months after initiating study intervention
|
Evaluated using RECIST version 1.1.
An estimate of DCR will be measured and reported with 95% exact confidence interval.
Participants who achieve a complete response, partial response, or stable disease for at least 6 months on the current protocol will be qualified as deriving benefit from therapy and will count towards the DCR measurement.
|
Up to 6 months after initiating study intervention
|
Mean plasma asparaginase activity
Time Frame: Up to 6 cycles from initiating study intervention (1 cycle = 21 days)
|
Will be reported with 95% confidence interval.
|
Up to 6 cycles from initiating study intervention (1 cycle = 21 days)
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Therapy induced changes in the tumor and tumor ecosystem
Time Frame: Up to 6 cycles from completing study intervention (1 cycle = 21 days)
|
Descriptive summary of cellular and molecular assays.
|
Up to 6 cycles from completing study intervention (1 cycle = 21 days)
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Charles D Lopez, OHSU Knight Cancer Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- STUDY00022141 (Other Identifier: OHSU Knight Cancer Institute)
- NCI-2021-09061 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Stage II Pancreatic Cancer AJCC v8
-
Thomas Jefferson UniversitySuspendedMalignant Solid Neoplasm | Gastric Adenocarcinoma | Pancreatic Ductal Adenocarcinoma | Stage II Pancreatic Cancer AJCC v8 | Stage III Pancreatic Cancer AJCC v8 | Colorectal Adenocarcinoma | Small Intestinal Adenocarcinoma | Clinical Stage III Gastric Cancer AJCC v8 | Stage IV Colorectal Cancer AJCC v8 | Stage IVA Colorectal Cancer AJCC... and other conditionsUnited States
-
Thomas Jefferson UniversityRecruitingStage II Pancreatic Cancer AJCC v8 | Stage 0 Pancreatic Cancer AJCC v8 | Stage I Pancreatic Cancer AJCC v8 | Stage IA Pancreatic Cancer AJCC v8 | Stage IB Pancreatic Cancer AJCC v8 | Stage IIA Pancreatic Cancer AJCC v8 | Stage IIB Pancreatic Cancer AJCC v8 | Resectable Pancreatic Ductal AdenocarcinomaUnited States
-
Thomas Jefferson UniversityNational Cancer Institute (NCI)CompletedStage II Pancreatic Cancer AJCC v8 | Stage III Pancreatic Cancer AJCC v8 | Stage IV Pancreatic Cancer AJCC v8 | Clinical Stage III Gastric Cancer AJCC v8 | Clinical Stage IV Gastric Cancer AJCC v8 | Stage IV Colorectal Cancer AJCC v8 | Stage IVA Colorectal Cancer AJCC v8 | Stage IVB Colorectal Cancer... and other conditionsUnited States
-
University of WashingtonNational Center for Complementary and Integrative Health (NCCIH); National...Not yet recruitingStage II Pancreatic Cancer AJCC v8 | Stage III Pancreatic Cancer AJCC v8 | Stage IV Pancreatic Cancer AJCC v8 | Clinical Stage III Gastric Cancer AJCC v8 | Clinical Stage IV Gastric Cancer AJCC v8 | Clinical Stage II Esophageal Adenocarcinoma AJCC v8 | Clinical Stage II Esophageal Squamous Cell... and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)WithdrawnPancreatic Ductal Adenocarcinoma | Stage II Pancreatic Cancer AJCC v8 | Stage III Pancreatic Cancer AJCC v8 | Stage IV Pancreatic Cancer AJCC v8 | Homologous Recombination Deficiency | Stage IIA Pancreatic Cancer AJCC v8 | Stage IIB Pancreatic Cancer AJCC v8 | ATM Gene Mutation | Deleterious BRCA1 Gene... and other conditions
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedAnatomic Stage III Breast Cancer AJCC v8 | Anatomic Stage IIIA Breast Cancer AJCC v8 | Anatomic Stage IIIB Breast Cancer AJCC v8 | Anatomic Stage IIIC Breast Cancer AJCC v8 | Prognostic Stage III Breast Cancer AJCC v8 | Prognostic Stage IIIA Breast Cancer AJCC v8 | Prognostic Stage IIIB Breast... and other conditionsUnited States
-
Ohio State University Comprehensive Cancer CenterRecruitingStage III Uterine Corpus Cancer AJCC v8 | Stage IVA Uterine Corpus Cancer AJCC v8 | Malignant Female Reproductive System Neoplasm | Stage I Cervical Cancer AJCC v8 | Stage IA Cervical Cancer AJCC v8 | Stage IA1 Cervical Cancer AJCC v8 | Stage IA2 Cervical Cancer AJCC v8 | Stage IB Cervical Cancer... and other conditionsUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingStage II Pancreatic Cancer AJCC v8 | Stage III Pancreatic Cancer AJCC v8 | Stage IV Pancreatic Cancer AJCC v8 | Stage IIA Pancreatic Cancer AJCC v8 | Stage IIB Pancreatic Cancer AJCC v8 | Advanced Pancreatic Ductal Adenocarcinoma | Unresectable Pancreatic Ductal AdenocarcinomaUnited States
-
University of California, San FranciscoBristol-Myers Squibb FoundationCompletedStage III Lung Cancer AJCC v8 | Stage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage IIIB Lung Cancer AJCC v8 | Malignant Neoplasm | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal... and other conditionsUnited States
-
M.D. Anderson Cancer CenterActive, not recruitingAnatomic Stage I Breast Cancer AJCC v8 | Anatomic Stage IA Breast Cancer AJCC v8 | Anatomic Stage IB Breast Cancer AJCC v8 | Anatomic Stage II Breast Cancer AJCC v8 | Anatomic Stage IIA Breast Cancer AJCC v8 | Anatomic Stage IIB Breast Cancer AJCC v8 | Anatomic Stage III Breast Cancer AJCC v8 | Anatomic... and other conditionsUnited States
Clinical Trials on Biopsy
-
UNICANCERNational Cancer Institute, FranceActive, not recruitingTriple-Negative Breast NeoplasmFrance
-
Postgraduate Institute of Medical Education and...CompletedLung Cancer | Endobronchial GrowthIndia
-
Centre Hospitalier Universitaire de NiceUnknownParodontitis Aggressive | Parodontitis ChronicFrance
-
Chandan SenTerminatedWound Leg | Non-Diabetic Patients | Chronic Ulcer Leg/FootUnited States
-
Duke UniversityCompletedInterstitial Lung DiseaseUnited States
-
Ardeshir RastinehadPhilips HealthcareRecruitingProstate Cancer | Prostate Disease | Elevated Prostate Specific Antigen | Family History of Prostate Cancer | Positive Digital Rectal ExamUnited States
-
Odense University HospitalNot yet recruitingProstate Cancer (Diagnosis)
-
Mayo ClinicErbe USA IncorporatedCompletedLung Diseases, Obstructive | Bronchi--Diseases | Lesions MassUnited States
-
Hordinsky, Maria K., MDTerminated