Trial Summary
What is the purpose of this trial?Pancreatic cancer is one of the leading causes of cancer deaths in the United States with limited treatment options, especially for those patients with metastatic disease. Combination treatment with cabozantinib and atezolizumab, has demonstrated safety for the treatment of other cancers and has shown promise in preclinical studies utilizing patient derived pancreas organoids. In this study, patients with refractory, metastatic pancreatic cancer will receive combination cabozantinib + atezolizumab and the efficacy of this treatment will be assessed through overall response rate (ORR), disease control rate (DCR), median overall survival (mOS), and median progression free survival (mPFS). Safety and tolerability of combination cabozantinib plus atezolizumab in metastatic pancreatic cancer patients will also be assessed and immune profiling pre- and post-treatment will be explored.
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you must not have received certain treatments like small molecule kinase inhibitors, cytotoxic, biologic, or other systemic anticancer therapies within 2-4 weeks before starting the study treatment. It's best to discuss your current medications with the trial team to ensure eligibility.
What data supports the idea that Atezolizumab + Cabozantinib for Pancreatic Cancer is an effective drug?
The available research does not provide specific data on the effectiveness of Atezolizumab + Cabozantinib for pancreatic cancer. Instead, it discusses other treatments and approaches, such as gemcitabine, multi-kinase inhibitors, and novel therapies targeting specific genetic changes in pancreatic cancer. These treatments have shown some promise in clinical trials, but there is no direct mention of Atezolizumab + Cabozantinib in the context of pancreatic cancer in the provided information.
12345What safety data exists for Atezolizumab and Cabozantinib treatment?
Atezolizumab, also known as Tecentriq, has been evaluated for safety in various cancers, including bladder cancer, non-small cell lung cancer, and breast cancer. Common adverse reactions include fatigue, decreased appetite, dyspnea, cough, nausea, musculoskeletal pain, and constipation. Grade 3 to 4 adverse events include dyspnea, pneumonia, hypoxia, hyponatremia, fatigue, anemia, and musculoskeletal pain. Immune-related adverse events include pneumonitis, hepatitis, colitis, and thyroid disease. The safety profile is considered acceptable, with manageable side effects. However, specific safety data for the combination of Atezolizumab and Cabozantinib in pancreatic cancer is not detailed in the provided research.
678910Is the drug Atezolizumab, Cabozantinib a promising treatment for pancreatic cancer?
Atezolizumab, known as Tecentriq, is a drug that helps the immune system fight cancer by blocking a protein that stops immune cells from attacking cancer cells. It has shown promise in treating other types of cancer, like bladder and lung cancer, by improving survival rates and response to treatment. While specific results for pancreatic cancer aren't provided, its success in other cancers suggests it could be promising for pancreatic cancer as well.
79111213Eligibility Criteria
Adults over 18 with stage IV pancreatic adenocarcinoma that has spread and is resistant to certain chemotherapies. They must have measurable disease, be in good physical condition (ECOG ≤1), and recovered from previous treatments' side effects. Participants need functioning organs/marrow, can't be pregnant or breastfeeding, must use contraception, and not have had specific prior treatments like cabozantinib or immune therapies.Inclusion Criteria
I am fully active and can carry on all my pre-disease activities without restriction.
I am 18 years old or older.
I have recovered from side effects of previous treatments, with only mild symptoms remaining.
+9 more
Exclusion Criteria
I have previously been treated with specific immune therapies.
I haven't taken any kinase inhibitor medication in the last 28 days.
I have pain from my cancer that isn't relieved by treatment.
+28 more
Participant Groups
The trial tests a combination of Cabozantinib + Atezolizumab for metastatic pancreatic cancer patients who haven't responded to standard treatments. It measures how well the treatment works (response rate), controls the disease, extends life without progression, overall survival time, safety/tolerability and examines immune changes before/after treatment.
1Treatment groups
Experimental Treatment
Group I: Cabozantinib 40mg + Atezolizumab 1200mgExperimental Treatment1 Intervention
Cabozantinib 40 mg, tablets, oral administration, once daily, continuously. Atezolizumab 1200 mg, administered intravenously, on Day 1 of every 21 day cycle.
Atezolizumab is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Tecentriq for:
- Melanoma
- Hepatocellular carcinoma
- Small cell lung cancer
- Non-small cell lung cancer
- Urothelial carcinoma
🇪🇺 Approved in European Union as Tecentriq for:
- Melanoma
- Hepatocellular carcinoma
- Small cell lung cancer
- Non-small cell lung cancer
- Urothelial carcinoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Arizona Cancer CenterTucson, AZ
Loading ...
Who Is Running the Clinical Trial?
University of ArizonaLead Sponsor
References
Future directions in the treatment of pancreatic cancer. [2022]Fewer than 20% of patients with pancreatic cancer present with disease macroscopically confined to the pancreas, and approximately 40% already have locally advanced disease. Based on data from the Gastrointestinal Tumor Study Group, adjuvant therapy with radiation and 5-fluorouracil has become standard practice in the United States; however, in other countries, adjuvant treatment has not been as widely accepted. Other issues include the potential of neoadjuvant therapy and optimal systemic management. The issue of second-line therapy has also been raised in the treatment of pancreatic carcinoma, after the establishment of gemcitabine as a first-line standard treatment approach, in which it achieves a significant clinical benefit response. Other combination partners with gemcitabine under investigation include the antimetabolite 5-fluorouracil, the topoisomerase-I inhibitor irinotecan, the taxane docetaxel, the platinum oxaliplatin, the multitargeted antifolate pemetrexed, the farnesyl transferase inhibitor R-115777, the anti-HER2/neu antibody trastuzumab, and the epidermal growth factor inhibitor cetuximab. Combined-modality approaches with gemcitabine and radiation are also under active investigation.
A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab-Paclitaxel and Gemcitabine in Advanced Solid Tumors. [2022]Label="LESSONS LEARNED">Itacitinib in combination with nab-paclitaxel plus gemcitabine demonstrated an acceptable safety profile with clinical activity in patients with advanced solid tumors including pancreatic cancer.The results support future studies of itacitinib as a component of combination regimens with other immunologic and targeted small molecule anticancer agents.
The development of multi-kinase inhibitors as pancreatic cancer therapeutics. [2022]Pancreatic cancer is an almost incurable malignancy whose incidence has increased over the past 30 years. Instead of pursuing the development of modalities utilizing 'traditional' cytotoxic chemotherapeutic agents, we have explored the possibilities of developing novel multi-kinase inhibitor drug combinations to kill this tumor type. Several approaches using the multi-kinase inhibitors sorafenib, regorafenib, and neratinib have been safely translated from the bench to the bedside, with objective anti-tumor responses. This review will discuss our prior preclinical and clinical studies and discuss future clinical opportunities in this disease.
Translational advances in pancreatic ductal adenocarcinoma therapy. [2023]Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that is most frequently detected at advanced stages, limiting treatment options to systemic chemotherapy with modest clinical responses. Here, we review recent advances in targeted therapy and immunotherapy for treating subtypes of PDAC with diverse molecular alterations. We focus on the current preclinical and clinical evidence supporting the potential of these approaches and the promise of combinatorial regimens to improve the lives of patients with PDAC.
From state-of-the-art treatments to novel therapies for advanced-stage pancreatic cancer. [2023]Improvements in the outcomes of patients with pancreatic ductal adenocarcinoma (PDAC) have lagged behind advances made in the treatment of many other malignancies over the past few decades. For most patients with PDAC, cytotoxic chemotherapy remains the mainstay of treatment. For patients with resectable disease, modified 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (mFOLFIRINOX) is the standard-of-care adjuvant therapy, although data from several randomized trials have shown improved outcomes with neoadjuvant treatment strategies. For patients with advanced-stage or metastatic disease, comprehensive genomic profiling has revealed several potentially actionable alterations in small subsets of patients and the feasibility of implementing such strategies is beginning to be confirmed. Novel therapies targeting certain aberrations, most notably BRCA1/2 mutations, mismatch repair (MMR) deficiencies or NTRK1-3 fusions, have shown considerable activity in clinical trials, and larotrectinib, entrectinib and pembrolizumab have received FDA approval for the treatment of patients with tumours harbouring NTRK fusions and MMR deficiencies, respectively, regardless of primary tumour histology. In this Review, we describe the available data on the activity of these and other agents in patients with PDAC. Our discussion is structured according to the acronym 'PRIME' to organize the various treatment strategies currently undergoing evaluation in clinical trials: Pathway inhibition, alteration of DNA Repair pathways, Immunotherapy, cancer Metabolism and targeting the Extracellular tumour microenvironment.
Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. [2020]Since the US FDA-approval of the first immune checkpoint inhibitor, anticytotoxic T-lymphocyte antigen-4 monoclonal antibody ipilimumab, for metastatic melanoma on 28 March 2011, another six agents have been granted use among a multitude of tumors, including renal cell cancer, Hodgkin lymphoma, urothelial carcinoma and non-small-cell lung cancer. The first anti-programmed cell death ligand-1 monoclonal antibody to receive the FDA approval, atezolizumab (Tecentriq®), has yielded promising results among international Phase III trials in triple-negative breast cancer and small-cell lung cancer, expanding the field of cancer immunotherapies. Herein, we review the pharmacodynamic and pharmacokinetic properties of atezolizumab, its safety and efficacy data from early clinical trials and summarize data from Phase III IMpassion130 trial, prompting FDA and EMA approval of atezolizumab in metastatic triple-negative breast cancer. Finally, implications for clinical use and ongoing research will be briefly discussed.
Atezolizumab: First Global Approval. [2019]Atezolizumab (Tecentriq™)-a monoclonal antibody targeting programmed death ligand 1 (PD-L1 or CD274 antigen)-is being developed by Genentech as treatment for a variety of haematological malignancies and solid tumours. It been approved in the US as a second-line therapy for urothelial carcinoma and is awaiting approval as a second-line therapy for non-small cell lung cancer. This article summarizes the milestones in the development of atezolizumab leading to this first approval for urothelial carcinoma.
Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences. [2022]Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies in patients with locally advanced or metastatic platinum-resistant urothelial carcinoma.
Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]Atezolizumab (Tecentriq, MPDL3280A; Genentech/Roche) is an FcγR binding-deficient, fully humanized IgG1 mAb designed to interfere with the binding of PD-L1 ligand to its two receptors, PD-1 and B7.1. By blocking the PD-L1/PD-1 immune checkpoint, atezolizumab reduces immunosuppressive signals found within the tumor microenvironment and, consequently, increases T-cell-mediated immunity against the tumor. Atezolizumab has been FDA approved as second-line therapy for advanced bladder cancer. This accelerated approval was based on phase II trial data in patients with metastatic bladder cancer that showed unexpected and durable tumor responses. In subjects whose tumors progressed on first-line platinum-based chemotherapy, the objective response rate was 15%, the complete response rate was 5%, and 1-year overall survival was 36%. In subjects that were chemotherapy naïve and cisplatin ineligible, the objective response rate was 24%, the complete response rate was 7%, and 1-year overall survival was 57%. Better responses were associated with higher PD-L1 expression on the tumor-infiltrating leukocytes. These data suggest that patients with advanced bladder cancer treated with atezolizumab have significantly better response rates and survival than historical controls treated with other second-line regimens. The toxicity profile of atezolizumab is also favorable. Trials are currently assessing whether atezolizumab is effective in earlier bladder cancer stages and in the first-line metastatic setting. Clin Cancer Res; 23(8); 1886-90. ©2016 AACR.
U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. [2022]On October 18, 2016, the FDA approved atezolizumab (TECENTRIQ; Genentech, Inc.) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose disease progressed during or following platinum-containing chemotherapy. Approval was based on demonstration of clinically meaningful improvements in overall survival (OS) and an acceptable safety profile in two randomized clinical trials (OAK and POPLAR). Median OS in OAK, a phase III trial, was 13.8 months [95% confidence interval (CI), 11.8-15.7] in the atezolizumab arm compared with 9.6 months (95% CI, 8.6-11.2) in the docetaxel arm [hazard ratio (HR) = 0.74; 95% CI, 0.63-0.87; P = 0.0004]. Median OS in POPLAR, a phase II trial, was 12.6 months (95% CI, 9.7-16.0) and 9.7 months (95% CI, 8.6-12.0; HR = 0.69; 95% CI, 0.52-0.92) for the atezolizumab and docetaxel arms, respectively. In patients treated with atezolizumab, the most common (≥20%) adverse reactions were fatigue, decreased appetite, dyspnea, cough, nausea, musculoskeletal pain, and constipation; the most common (≥2%) grade 3 to 4 adverse events were dyspnea, pneumonia, hypoxia, hyponatremia, fatigue, anemia, musculoskeletal pain, aspartate aminotransferase increase, alanine aminotransferase increase, dysphagia, and arthralgia. Clinically significant immune-related adverse events for patients receiving atezolizumab included 1.4% incidence each of grade 3 to 4 pneumonitis, hepatitis, colitis, and thyroid disease. Clin Cancer Res; 23(16); 4534-9. ©2017 AACR.
Atezolizumab for the treatment of colorectal cancer: the latest evidence and clinical potential. [2022]Atezolizumab is a fully humanized, engineered monoclonal antibody that specifically targets PD-L1, key molecule in the cancer-immunity pathway. Atezolizumab is currently approved for the treatment of metastatic non-small-cell lung cancer and advanced urothelial carcinomas. Areas covered: In this review, we will present the available data supporting the efficacy of atezolizumab for the treatment of metastatic colorectal cancer (mCRC). We will also provide an update on the ongoing/future clinical trials evaluating the role of atezolizumab for the treatment of CRC in different settings (alone or in combination with other checkpoint inhibitors and/or targeted therapies). So far, a small subgroup of mCRC (those with deficiency in mismatch repair - dMMR) appears to benefit significantly from checkpoint inhibitors. As expected, further research is needed to develop biomarkers, effective therapeutic strategies and novel combinations to overcome immune escape resistance and achieve better responses with minimal toxicities. Expert opinion: Interim analyses from ongoing early-phase studies in mCRC have shown encouraging activity of atezolizumab in combination with chemotherapy and/or targeted therapies, especially with MEK inhibitor cobimetinib. Within the next few years, this PD-L1 checkpoint inhibitor will likely be included as one of the treatment options for CRC, at least for patients with dMMR.
Efficacy of neoadjuvant atezolizumab treatment in patients with advanced urothelial bladder cancer according to the BASQ classification: a study protocol for an open-label, two-cohort, phase II trial. [2021]Atezolizumab is a programmed death ligand-1 inhibitor for urothelial bladder cancer treatment. Atezolizumab has become the standard therapy for patients with urothelial bladder cancer who are not responding to cisplatin-based chemotherapy and is also used as a first-line treatment in cisplatin-ineligible patients. However, the efficacy of atezolizumab as a neoadjuvant chemotherapy for radical cystectomy has not yet been published and is still under study. This trial investigates the effectiveness of basal/squamous-like (BASQ) classification in the selection of an effective target group of patients with muscle-invasive bladder cancer (MIBC) for neoadjuvant atezolizumab treatment.
Extension of the Alternative Intravenous Dosing Regimens of Atezolizumab into Combination Settings through Modeling and Simulation. [2022]Atezolizumab is approved as an intravenous (IV) infusion for use as a single agent and in combination with other therapies in a number of indications. The objectives of this publication are to characterize atezolizumab pharmacokinetics (PK) across indications with the available clinical data from one phase I and eight phase III studies, to determine the exposure-response (ER) relationships in combination settings across a variety of tumor types, and to provide the clinical safety to support the extension of the 840 mg q2w, 1200 mg q3w, and 1680 mg q4w IV dosing regimens across various indications in combination settings. Across all clinical studies, atezolizumab PK remained in the dose-linear range and were similar across tumor types when used in combination therapy or as a monotherapy. In the combination studies, efficacy was independent of the exposures tested and there was no significant increase in adverse events with increasing atezolizumab exposure (flat ER). The safety profile of atezolizumab in the individual combination studies was generally consistent with the established safety profile of atezolizumab, the combination partners, and the disease under study. The similar atezolizumab PK across monotherapy and combination therapy settings as well as the flat ER in new tumor types and combination therapies support the use of the 3 interchangeable atezolizumab dosing regimens in the combination setting. Atezolizumab is now approved with 3 interchangeable IV dosing regimens of 840 mg q2w, 1200 mg q3w, and 1680 mg q4w for single-agent and combination therapy use in the USA and EU.