Atezolizumab + Bevacizumab for Gastrointestinal Cancer
(MRD-GI Trial)
Recruiting in Palo Alto (17 mi)
+2 other locations
Overseen byJohn L. Marshall, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Georgetown University
Must not be taking: NSAIDs, Immunosuppressants, Anticoagulants, others
Disqualifiers: Autoimmune disease, Cardiovascular disease, Active infection, others
Stay on Your Current Meds
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This study is a non-randomized, open-label, multi-cohort, multi-site, pilot feasibility therapeutic trial. The study will enroll 20 patients across 4 cohorts (CRC, gastric, PDAC, and HCC/intra-hepatic-/extra-hepatic-, gall bladder adenocarcinomas) diagnosed with histologically confirmed GI cancers. These patients will have already completed all Standard of Care (SOC) treatments (including neoadjuvant, surgery, local therapies, and/or adjuvant therapy as applicable), as defined by the treating primary physician or research team, with curative intent but have a positive SignateraTM tumor-informed ctDNA test and NED radiographically by standard imaging within 28 days prior to enrollment and within 1 year of completing all curative-intent therapy. All patients will be treated with intravenous (IV) atezolizumab 1200 mg IV and bevacizumab 15 mg/kg on Day 1 of 21-day cycles until disease recurrence, ctDNA POD, unacceptable toxicity, or subject withdrawal of consent with a maximum 12 month total duration of study therapy. Atezolizumab and bevacizumab drug will be provided.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. However, it mentions that certain medications, like high-dose aspirin, clopidogrel, and chronic NSAIDs, should not be used close to the start of the study treatment. It's best to discuss your current medications with the study team to get specific guidance.
What data supports the effectiveness of the drug combination Atezolizumab and Bevacizumab for gastrointestinal cancer?
Bevacizumab (Avastin) has shown significant benefits in improving survival and delaying disease progression when combined with chemotherapy in colorectal cancer, which is a type of gastrointestinal cancer. This suggests that Bevacizumab may also be effective in other gastrointestinal cancers when used in combination with other treatments like Atezolizumab.
12345Is the combination of Atezolizumab and Bevacizumab generally safe for humans?
The combination of Atezolizumab (Tecentriq) and Bevacizumab (Avastin) has been studied for safety in various conditions, including liver cancer. Common side effects of Bevacizumab include high blood pressure, protein in urine, and bleeding, which are usually mild to moderate and manageable. Serious but less common side effects include issues with wound healing and gastrointestinal perforation.
678910How is the drug combination of Atezolizumab and Bevacizumab unique for treating gastrointestinal cancer?
The combination of Atezolizumab and Bevacizumab is unique because it targets both the immune system and blood vessel growth in tumors. Atezolizumab helps the immune system recognize and attack cancer cells, while Bevacizumab blocks the growth of blood vessels that supply nutrients to tumors, potentially enhancing the overall anticancer effect.
34111213Eligibility Criteria
Adults who've completed all standard treatments for certain GI cancers (like colorectal, stomach, liver cancer) with curative intent but still have detectable ctDNA. They must be in good physical condition, not pregnant or breastfeeding, willing to use contraception and not have any active infections or severe health conditions that could interfere with the trial.Inclusion Criteria
I am 18 years old or older.
Signed Informed Consent Form
Women of childbearing potential must have a negative serum test result within 28 days prior to initiation of study treatment
+16 more
Exclusion Criteria
I have high calcium levels in my blood that are causing symptoms.
I might have or know I have cancer that has come back or spread within the last 28 days.
I have a serious heart condition.
+30 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
4 weeks
1 visit (in-person)
Treatment
Participants receive intravenous atezolizumab and bevacizumab on Day 1 of 21-day cycles for a maximum of 12 months
12 months
Every 3 weeks (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
12 weeks
2 visits (in-person)
Open-label extension (optional)
Participants may opt into continuation of treatment long-term
Long-term
Participant Groups
The trial is testing Atezolizumab and Bevacizumab on patients with GI cancers who are ctDNA positive after standard treatment. It's an open-label study where everyone gets the drugs through IV every 21 days for up to a year unless their disease returns or side effects become too much.
1Treatment groups
Experimental Treatment
Group I: Atezolizumab plus BevacizumabExperimental Treatment2 Interventions
atezolizumab 1200 mg and bevacizumab 15 mg/kg given intravenously on Day 1 of each 21-day cycle (every 3 weeks \[Q3W\]) for a maximum of 12 months.
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:
Georgetown Lombardi Comprehensive Cancer CenterWashington, United States
John Theurer Cancer Center at Hackensack University Medical CenterHackensack, NJ
Medstar Washington Hospital CenterWashington, United States
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Who Is Running the Clinical Trial?
Georgetown UniversityLead Sponsor
Genentech, Inc.Industry Sponsor
Natera, Inc.Industry Sponsor
References
The future development of bevacizumab in colorectal cancer. [2015]Bevacizumab (Avastin), the first approved therapy designed to inhibit tumor angiogenesis, has significant clinical benefits in the management of colorectal cancer (CRC). When bevacizumab is added to IFL (5-fluorouracil [5-FU]/leucovorin [LV]/irinotecan [Camptosar)]) as first-line therapy for metastatic CRC, significant overall and progression-free survival benefits are obtained. Similar survival benefits may be achieved when bevacizumab is added to 5-FU/LV alone. In addition, additive and synergistic effects with a range of chemotherapeutic agents illustrate that bevacizumab has considerable potential in combination with existing therapeutic options. Clinical data indicate that bevacizumab is the only agent in addition to chemotherapy that has demonstrated survival benefit in the first- and second-line settings. In addition, bevacizumab is expected to produce clinical benefit in the adjuvant setting: inhibition of vascular endothelial growth factor should prevent the angiogenic switch in micrometastases, which is a key factor in malignancy. The clinical program is examining the activity of bevacizumab in combination with the likely future standard of care in both the metastatic and adjuvant treatment settings. Phase III trials (NO16966C, CONcePT and TREE-2) are studying the benefit of combining bevacizumab with oxaliplatin (Eloxatin)-based regimens. Similarly, in the adjuvant setting, phase III trials are assessing the efficacy and tolerability of bevacizumab in combination with oxaliplatin-based chemotherapy (AVANT, NSABP C-08).
Expanding the clinical development of bevacizumab. [2019]Bevacizumab (Avastin; Genentech, Inc.; South San Francisco, CA) is a recombinant, humanized monoclonal antibody to vascular endothelial growth factor, a key regulator of tumor angiogenesis. Bevacizumab demonstrated potent antitumor activity in preclinical models and has also shown biologic activity and clinical benefit in clinical studies. Notably, a randomized, placebo-controlled phase II trial in renal cell carcinoma demonstrated a significantly longer time to tumor progression with bevacizumab monotherapy. Furthermore, in a phase III trial for untreated advanced colorectal cancer, the addition of bevacizumab to chemotherapy led to significantly longer overall survival and progression-free survival times than chemotherapy alone. The clinical development of bevacizumab has been expanded to include confirmatory phase III trials and exploratory phase II trials in a variety of solid tumors and hematologic malignancies. Treatment regimens being examined include bevacizumab alone and in combination with conventional chemotherapy, radiation, immune therapy, and biologically targeted agents.
Bevacizumab. [2020]Bevacizumab (Avastin; Genentech/Roche), an antibody against vascular endothelial growth factor, was approved by the US FDA in February 2004 for the first-line treatment of metastatic colorectal cancer in combination with 5-fluorouracil-based chemotherapy. It is the first approved agent to target tumour angiogenesis.
Phase IV study of bevacizumab in combination with infusional fluorouracil, leucovorin and irinotecan (FOLFIRI) in first-line metastatic colorectal cancer. [2022]Bevacizumab (Avastin) significantly improves overall survival (OS) and progression-free survival (PFS) when combined with first-line irinotecan (IFL) plus bolus 5-fluorouracil (5-FU) and leucovorin (LV) in patients with metastatic colorectal cancer (CRC). This open-label, phase IV trial evaluated the efficacy and safety of first-line bevacizumab in combination with IFL and infusional 5-FU/LV (FOLFIRI).
Targeted therapy of colorectal cancer: clinical experience with bevacizumab. [2019]Advanced colorectal cancer remains an urgent health concern, despite improvements in systemic chemotherapy. Targeted therapeutics promise effective tumor therapy with minimal side effects. Angiogenesis (the formation of new blood vessels) is essential for tumor growth and metastasis and may be an ideal target in the search for new antineoplastic agents. Vascular endothelial growth factor is one of the best characterized of the proangiogenic growth factors that regulate angiogenesis and is a logical target in colorectal cancer therapy. Bevacizumab (Avastin; Genentech Inc.; South San Francisco, CA), a humanized murine monoclonal antibody directed at vascular endothelial growth factor, is being evaluated in the treatment of various types of cancer. It has shown promising efficacy in phase II clinical trials in patients with metastatic colorectal cancer. Addition of bevacizumab at a dose of 5 mg/kg to chemotherapy (5-fluorouracil plus leucovorin) resulted in a higher objective response rate (40% versus 17%), longer time to disease progression (9.0 versus 5.2 months), and longer median survival time (21.5 versus 13.8 months). Hypertension and thrombosis were the principal safety concerns, but were manageable. Further phase II/III studies of bevacizumab, administered with 5-fluorouracil plus leucovorin, with or without irinotecan and/or oxaliplatin, in colorectal cancer, are under way.
Managing patients treated with bevacizumab combination therapy. [2015]The anti-angiogenic agent bevacizumab (Avastin) has been rationally designed to target vascular endothelial growth factor (VEGF), a key mediator of tumor angiogenesis. Based on its limited roles in adults, VEGF inhibition using bevacizumab would be expected to have limited side effects. Furthermore, because its mechanism of action is different to that of standard chemotherapeutic agents, bevacizumab would not be expected to cause typical cytotoxic agent-related toxicity or to exacerbate the toxicity of concomitant chemotherapy. We have reviewed clinical trials published to date, primarily in metastatic colorectal cancer, and describe the safety profile of bevacizumab. The review focuses on hypertension, proteinuria, arterial thrombosis, effects on wound healing, bleeding and gastrointestinal (GI) perforation, which are the principal bevacizumab-related events seen in clinical trials. These events are for the most part mild to moderate in severity and clinically manageable (hypertension, proteinuria, minor bleeding) or occur uncommonly (wound healing complications, GI perforations and arterial thrombosis). The side-effect profile of bevacizumab makes it a suitable adjunct to standard chemotherapy in settings where efficacy has been demonstrated, and it is now approved for use in the USA, the European Union and other markets worldwide.
Efficacy and safety of atezolizumab plus bevacizumab in Korean patients with advanced hepatocellular carcinoma. [2022]Atezolizumab plus bevacizumab (Ate/Bev) has demonstrated efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the phase III trial. Further evaluation is necessary to investigate the safety and efficacy of Ate/Bev in real settings.
Incidence and management of bevacizumab-related toxicities in colorectal cancer. [2022]Bevacizumab, a recombinant, humanised monoclonal antibody against vascular endothelial growth factor, when used in combination with intravenous 5-fluorouracil (5-FU)-based chemotherapy as first-line treatment of metastatic colorectal cancer (CRC) improves survival. In a randomised, placebo-controlled Phase III study, the addition of bevacizumab to irinotecan/5-FU/leucovorin (IFL) resulted in significant improvement in survival compared with IFL alone, which led to its approval for first-line use in CRC. Bevacizumab also demonstrates improved efficacy in combination with 5-FU/LV over chemotherapy alone when data were pooled from two randomised Phase II studies utilising bevacizumab with 5-FU/leucovorin, and also in a third treatment arm of bevacizumab/5-FU/LV of a randomised Phase III study. More recently, in the second-line setting, bevacizumab in combination with FOLFOX improved survival from 10.8 to 12.9 months in the ECOG 3200 trial. Clinical activity with the addition of bevacizumab to oxaliplatin and either 5-FU or capecitabine-based regimens has also been shown in TREE-2, and activity with the combination of bevacizumab and the EGFR inhibitor cetuximab has been documented in BOND-2. In this study, bevacizumab was generally well-tolerated with no unexpected toxicities when combined with cetuximab. A few toxicities were uniformly encountered in all of the above studies, in particular grade 3 medically-manageable hypertension (3 - 16%). In addition, other toxicities were haemorrhage (2 - 9.3%), gastrointestinal perforation (1.5%), arterial thromboembolism (3.8%), wound healing (1 - 2%) and proteinuria (1 - 2%). As bevacizumab is becoming widely used in general oncology practice, it is important to understand the toxicities which can arise and to develop practice guidelines for their management. This review addresses the toxicities noted in trials using bevacizumab for the treatment of CRC and provides recommendations for toxicity management.
Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. [2021]The combination of atezolizumab and bevacizumab showed encouraging antitumor activity and safety in a phase 1b trial involving patients with unresectable hepatocellular carcinoma.
Adverse events as potential predictive factors of therapeutic activity in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab. [2023]To investigate the possible correlation between the development of adverse events (AEs) and prognosis in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Atez/Bev).
Safety and Clinical Activity of Atezolizumab Plus Bevacizumab in Patients with Ovarian Cancer: A Phase Ib Study. [2021]Atezolizumab has shown antitumor activity in patients with ovarian cancer. Dual blockade of programmed death-ligand 1 (PD-L1) and VEGF enhances anticancer immunity and augments antitumor activity in several cancers. The safety and efficacy of atezolizumab plus bevacizumab were evaluated in patients with ovarian cancer.
Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. [2022]Bevacizumab (Avastin; Genentech Inc, South San Francisco, CA), a recombinant, humanized anti-vascular endothelial growth factor monoclonal antibody that inhibits tumor angiogenesis, has demonstrated survival benefit in patients with previously untreated metastatic colorectal cancer when combined with irinotecan/fluorouracil (FU)/leucovorin (LV; IFL). Three randomized clinical studies have evaluated bevacizumab in combination with FU/LV alone. A combined analysis of raw data from these studies was performed to better assess the efficacy of bevacizumab with FU/LV.
Drug insight: antiangiogenic therapies for gastrointestinal cancers--focus on monoclonal antibodies. [2015]Tumor angiogenesis is strongly induced by vascular endothelial growth factor (VEGF), which is overexpressed in most human gastrointestinal cancers. VEGF overexpression is known to be associated with poor prognosis and survival in patients with various solid tumors. The humanized monoclonal anti-VEGF antibody bevacizumab (Avastin, Genentech Inc., South San Francisco, CA) is a prototypic antiangiogenic compound, and has proven therapeutic benefit combined with conventional chemotherapy-namely, significantly improved progression-free survival in patients with metastatic colorectal cancer. Bevacizumab is the only anti-VEGF antibody that has been approved by the FDA and the European Medicines Agency for the treatment of metastatic colorectal cancer. Several ongoing clinical studies are evaluating the potential of bevacizumab therapy for other gastrointestinal cancers, in combination with chemotherapy, other targeted therapies and/or radiation. Soluble chimeric receptors, tyrosine kinase inhibitors, and monoclonal antibodies against VEGF and molecular targets in the integrin and Delta-like protein 4-Notch pathways are being developed. As tumors acquire resistance to anti-VEGF therapy, further development of antiangiogenic and vascular targets and therapy is warranted.