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Not recruiting
Phase 1

Calaspargase Pegol-Mnkl & Cobimetinib

Sponsor:

OHSU Knight Cancer Institute

Code:

NCT05034627

Conditions

Locally Advanced Pancreatic Adenocarcinoma

Metastatic Pancreatic Adenocarcinoma

Stage II Pancreatic Cancer AJCC v8

Stage IIA Pancreatic Cancer AJCC v8

Stage IIB Pancreatic Cancer AJCC v8

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biopsy

Calaspargase Pegol-mknl

Cobimetinib

Study Details

Brief summary:

This phase I trial tests the safety, side effects, and best dose of calaspargase pegol-mknl in combination with cobimetinib in treating patients with pancreatic cancer that has spread to nearby tissue or lymph nodes (locally advanced) or has spread to other places in the body (metastatic). Cobimetinib attacks a protein called MEK that has been known to stimulate cells that promote the growth of cancer cells in the body. Calaspargase pegol-mknl is an enzyme that converts the amino acid L-asparagine into aspartic acid and ammonia. Many types of cancer cell rely on the amino acid L-asparagine, and depleting this amino acid with calaspargase pegol-mknl starves cancer cells of this nutrient. Attacking the MEK protein with cobimetinib is thought to further prevent cancer cells from using this amino acid, causing them to die. Giving calaspargase pegol-mknl in combination with cobimetinib may help control the disease in patients with pancreatic cancer.

Conditions

Locally Advanced Pancreatic Adenocarcinoma

Metastatic Pancreatic Adenocarcinoma

Stage II Pancreatic Cancer AJCC v8

Stage IIA Pancreatic Cancer AJCC v8

Stage IIB Pancreatic Cancer AJCC v8

Study ID

NCT05034627

Start date

Aug 9, 2022

Status verified date

Oct, 2024

Completion date

Oct 1, 2026

Anticipated

Primary completion date

Dec 16, 2025

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

15 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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.

Interventions

Biopsy

Undergo biopsy

Calaspargase Pegol-mknl

Given IV

Cobimetinib

Given PO

Primary outcome measure

  • Incidence of dose-limiting toxicities (DLTs) [ Time Frame: Up to cycle 2 day 21 (1 cycle = 21 days) ]

Central Contacts and Locations

Locations

OHSU Knight Cancer Institute

Recruiting

Portland, Oregon, United States, 97239

Contacts

Charles D. Lopez

503-494-8321lopezc@ohsu.edu

Principal Investigator:

Charles D. Lopez

More Information

Sponsor

OHSU Knight Cancer Institute

Last update posted

Oct 28, 2024

Last verified

Oct, 2024

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-02. This information was provided to ClinicalTrials.gov by OHSU Knight Cancer Institute on 2024-10-28. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.