Calaspargase + Cobimetinib for Pancreatic Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: OHSU Knight Cancer Institute
Must not be taking: CYP3A inhibitors, CYP3A inducers
Disqualifiers: Chronic pancreatitis, Cardiac disease, others
No Placebo Group
Trial Summary
What is the purpose of this trial?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.
Do I have to stop taking my current medications for the trial?
The trial protocol does not specify if you must stop all current medications, but you cannot use other anti-cancer therapies or certain medications like strong CYP3A inhibitors or inducers within 7 days before starting the trial. Check with the trial team for specific guidance on your medications.
What data supports the idea that Calaspargase + Cobimetinib for Pancreatic Cancer is an effective treatment?
The available research does not provide specific data on the effectiveness of Calaspargase + Cobimetinib for Pancreatic Cancer. Instead, it discusses other treatments like FOLFIRINOX and GEMNAB, which have shown improved survival rates for advanced pancreatic cancer compared to single-agent gemcitabine. Additionally, PEGylated curcumin has been shown to inhibit pancreatic cancer cell growth more effectively than free curcumin. However, there is no direct comparison or data available for Calaspargase + Cobimetinib in the provided information.
12345What safety data is available for Calaspargase + Cobimetinib in pancreatic cancer treatment?
The provided research does not directly address the safety data for the combination of Calaspargase and Cobimetinib in pancreatic cancer. However, it includes a study on the safety and toxicity of Calaspargase Pegol in childhood acute lymphoblastic leukemia, which may provide some insights into its safety profile. Additionally, there is a study on the safety of Pegaspargase in combination with gemcitabine in advanced metastatic solid tumors, which could offer relevant information. No specific safety data for Cobimetinib in this context is mentioned in the provided research.
46789Is the drug Calaspargase Pegol-mknl, Cobimetinib a promising treatment for pancreatic cancer?
The combination of Calaspargase Pegol-mknl and Cobimetinib shows promise for pancreatic cancer treatment. Cobimetinib, when used with another drug, has shown positive results in targeting specific mutations in pancreatic cancer, suggesting potential effectiveness.
2581011Eligibility Criteria
Adults with advanced or metastatic pancreatic cancer who have not responded to, cannot tolerate, or refused standard treatments like Gemcitabine-based therapy or FOLFORINOX. They must be in relatively good health (ECOG 0-2), have acceptable blood counts and organ function, and agree to use non-hormonal contraception. Pregnant women, those with certain heart conditions, severe allergies to trial drugs, uncontrolled medical issues, or recent other cancer therapies are excluded.Inclusion Criteria
My pancreatic cancer is confirmed and has spread.
I can take care of myself and am up and about more than half of the day.
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)
+14 more
Exclusion Criteria
I am allergic to calaspargase pegol-mknl, cobimetinib, or similar drugs.
I am not taking any strong or moderate drugs that affect liver enzymes.
My high blood pressure is not under control.
+14 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants 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.
18 weeks
6 cycles, each with 1 in-person visit
Follow-up
Participants are monitored for safety and effectiveness after treatment
6 months
Follow-up visits at 3 and 6 months
Participant Groups
The trial is testing the combination of Calaspargase Pegol-mknl and Cobimetinib for safety and optimal dosing against pancreatic cancer that has spread. Calaspargase Pegol-mknl deprives cancer cells of a needed amino acid while Cobimetinib blocks a protein that helps these cells grow.
1Treatment groups
Experimental Treatment
Group I: Treatment (calaspargase pegol-mknl, cobimetinib)Experimental Treatment3 Interventions
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.
Calaspargase Pegol-mknl is already approved in European Union, United States for the following indications:
🇪🇺 Approved in European Union as Besponsa for:
- Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL)
🇺🇸 Approved in United States as Besponsa for:
- Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients 1 year and older
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
OHSU Knight Cancer InstitutePortland, OR
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Who Is Running the Clinical Trial?
OHSU Knight Cancer InstituteLead Sponsor
Genentech, Inc.Industry Sponsor
Servier Pharmaceuticals, LLCCollaborator
Oregon Health and Science UniversityCollaborator
References
Front-line treatment of inoperable or metastatic pancreatic cancer with gemcitabine and capecitabine: an intergroup, multicenter, phase II study. [2022]To evaluate the efficacy and toxicity of gemcitabine (GEM) combined with capecitabine (CAP) in untreated patients with inoperable or metastatic pancreatic cancer.
Randomized Phase III Study of FOLFOX Alone or With Pegilodecakin as Second-Line Therapy in Patients With Metastatic Pancreatic Cancer That Progressed After Gemcitabine (SEQUOIA). [2022]SEQUOIA compared efficacy and safety of adding pegilodecakin (PEG), a pegylated recombinant human interleukin (IL)-10, with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) in patients following progression on first-line gemcitabine-containing therapy with metastatic pancreatic ductal adenocarcinoma (PDAC).
The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer. [2023]Gemcitabine-nab-paclitaxel (GEMNAB) and fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) both improve survival of patients with advanced pancreatic cancer when compared with single-agent gemcitabine in clinical trials.
Polyethylene glycosylated curcumin conjugate inhibits pancreatic cancer cell growth through inactivation of Jab1. [2022]Jab1 (Jun activation domain binding protein 1), integrated into COP9 signalosome complex (CSN), induces protein instability of many tumor suppressors and cell cycle regulators and is therefore a novel target in cancer therapy. Curcumin, an inhibitor of Jab1/CSN-associated kinase(s), has been reported to suppress tumor growth; however, curcumin is highly hydrophobic, and this feature prevents its usage as an antitumor drug. To increase the solubility and targeted delivery, we generated a water-soluble polyethylene glycol (PEG)-conjugated curcumin system, in which curcumin is covalently linked to PEG(35kD). PEGylated curcumin showed much greater reduction of cell growth than free curcumin in pancreatic cancer cells. Cells treated with PEGylated curcumin had increased arrest at the mitotic phase with the formation of abnormal multinucleated cells, indicating that this compound affects cell cycle progression, which may contribute to cell growth inhibition. The stabilities of Jab1 target proteins were also examined. PEGylated curcumin increased protein stability of these proteins in pancreatic cancer cells and directly inhibited the activity of Jab1/CSN-associated kinases. Moreover, the inhibitory effect of PEGylated curcumin on cell proliferation was blunted in pancreatic cancer cells with Jab1 knockdown. The results suggest that PEGylated curcumin inhibits cell proliferation through suppression of Jab1/CSN activity. More importantly, the new compound sensitized pancreatic cancer cells to gemcitabine-induced apoptosis and cell proliferation inhibitory effects. Collectively, the PEGylated curcumin conjugate has much more potent effects on pancreatic cancer cell growth inhibition than free curcumin. The current study provides a biologic rationale to treat patients with pancreatic adenocarcinoma with the nontoxic phytochemical conjugated to PEG for systemic delivery.
Ipilimumab and Gemcitabine for Advanced Pancreatic Cancer: A Phase Ib Study. [2022]Pancreatic ductal adenocarcinoma (PDAC) remains resistant to chemotherapy and immunotherapy individually because of its desmoplastic stroma and immunosuppressive tumor microenvironment. Synergizing cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) immune checkpoint blockade with chemotherapy could overcome these barriers. Here we present results of a phase Ib trial combining ipilimumab and gemcitabine in advanced PDAC.
Phase 1b study of galunisertib in combination with gemcitabine in Japanese patients with metastatic or locally advanced pancreatic cancer. [2022]Transforming growth factor-beta inhibitors may enhance the antitumor activity of gemcitabine with acceptable safety and tolerability. This open-label, multicenter, non-randomized phase 1b study assessed the safety/tolerability, pharmacokinetics, and tumor response of galunisertib plus gemcitabine in Japanese patients with advanced or metastatic pancreatic cancer.
Galunisertib plus gemcitabine vs. gemcitabine for first-line treatment of patients with unresectable pancreatic cancer. [2022]Galunisertib is the first-in-class, first-in-human, oral small-molecule type I transforming growth factor-beta receptor (ALK5) serine/threonine kinase inhibitor to enter clinical development. The effect of galunisertib vs. placebo in patients with unresectable pancreatic cancer was determined.
Efficacy and Toxicity of Pegaspargase and Calaspargase Pegol in Childhood Acute Lymphoblastic Leukemia: Results of DFCI 11-001. [2021]Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia (ALL) Consortium Protocol 11-001 assessed efficacy and toxicity of calaspargase pegol (calaspargase), a novel pegylated asparaginase formulation with longer half-life, compared with the standard formulation pegaspargase.
A multicenter, open-label, Phase 1 study evaluating the safety and tolerability of pegaspargase in combination with gemcitabine in advanced metastatic solid tumors and lymphoma. [2022]To evaluate the maximum tolerated dose, safety profile, pharmacokinetics, and pharmacodynamics of pegaspargase (PEG-ASP) in combination with gemcitabine in patients with advanced metastatic solid tumors and lymphoma.
Dose finding and early efficacy study of gemcitabine plus capecitabine in combination with bevacizumab plus erlotinib in advanced pancreatic cancer. [2022]This study evaluated safety and efficacy of chemotherapy (gemcitabine plus capecitabine) plus bevacizumab/erlotinib in advanced pancreatic cancer because dual epidermal growth factor receptor/vascular endothelial growth factor blockade has a rational biologic basis in this malignancy.
Molecular Targeting of a BRAF Mutation in Pancreatic Ductal Adenocarcinoma: Case Report and Literature Review. [2021]Current standard-of-care treatment for advanced pancreatic ductal adenocarcinoma is mainly based on conventional cytotoxic chemotherapy. Until recently, no randomized clinical trials had shown any clinically meaningful outcome benefit from targeted therapy in this indication. This is in contrast to many other tumor types. The majority of pancreatic tumors are driven by KRAS mutations, which are generally not amenable to targeted therapy. Driving mutations in the BRAF oncogene have proven to be an interesting molecular target in the management of advanced melanoma and colorectal adenocarcinoma and can be found in 3% of patients with advanced pancreatic ductal adenocarcinoma. Here, we report objective tumor response to treatment with the combination of the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib in a patient with poorly differentiated, V600E mutant, advanced pancreatic ductal adenocarcinoma.