Atezolizumab + Bevacizumab for Rare Cancers

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Immunostimulants

Disqualifiers: Autoimmune disease, Severe infection, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 2

Duration: 21-day cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of two medicines, atezolizumab (Tecentriq) and bevacizumab (Avastin), in combating rare solid tumors. These medicines are a type of immunotherapy, helping the body's immune system attack cancer cells and prevent their growth or spread. The trial seeks participants with specific rare cancers, such as certain neuroendocrine tumors, mesothelioma, or HPV-associated cancers, that have spread or recurred and cannot be surgically removed. Participants should have previously tried other treatments that were ineffective or intolerable. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using a somatostatin analogue for symptom control, you must be on a stable dose for 56 days before joining the study. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that atezolizumab and bevacizumab are likely to be safe for humans?

A previous study found that the combination of atezolizumab and bevacizumab generally causes manageable side effects, consistent with known effects of each drug and the conditions they treat. Some serious and life-threatening side effects have been reported with this treatment, but these risks are usually well-understood and monitored in clinical settings.

Atezolizumab and bevacizumab are monoclonal antibodies already used to treat other cancers, offering some reassurance about their use. Patients should be aware of possible side effects and discuss these with their doctors before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of atezolizumab and bevacizumab for rare cancers because these drugs work together in a unique way. Atezolizumab is an immunotherapy that helps the immune system recognize and attack cancer cells by targeting the PD-L1 protein, while bevacizumab is an antibody that inhibits blood vessel growth in tumors by targeting the VEGF protein. This combo could be more effective than traditional chemotherapy or radiation because it not only boosts the body's natural defenses but also cuts off the tumor's blood supply, potentially leading to better outcomes for patients with rare cancers.

What evidence suggests that atezolizumab and bevacizumab might be effective for rare cancers?

Research has shown that combining atezolizumab and bevacizumab may help treat certain cancers. In earlier studies, this combination extended patients' lives and slowed tumor growth or spread. For instance, 82% of patients were alive at 6 months, and 65% at 12 months. Other studies found that patients went up to 23.2 months without their cancer worsening. This trial will assess the effectiveness of the atezolizumab and bevacizumab combination in managing rare solid tumors by enhancing the body's immune response against cancer. ^{4 6 7 8 9}

Who Is on the Research Team?

Kanwal P. Raghav

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with rare solid tumors like certain types of lung, anal, cervical, and other cancers. Participants must have measurable disease growth, adequate liver/kidney function, and be able to follow the study plan. They should not have severe allergies or autoimmune diseases, recent cancer treatments or investigational therapies within 28 days prior to the study.

Inclusion Criteria

Ability to comply with the study protocol, in the investigator's judgment

My cancer type matches the specific criteria listed.

My liver and kidney are working well.

Exclusion Criteria

I have not been excluded due to previous treatments or medications.

I do not have autoimmune diseases, organ transplants, serious lung, infectious, or heart conditions.

Pregnancy, breastfeeding, or intention to become pregnant during the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atezolizumab and bevacizumab intravenously over 60 minutes on day 1, with courses repeating every 21 days in the absence of disease progression or unacceptable toxicity

21-day cycles

1 visit every 21 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 3 months

Up to 4 years

1 visit every 3 months (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Bevacizumab

Trial Overview

The trial tests how well atezolizumab (an immunotherapy drug) combined with bevacizumab (a drug that inhibits blood vessel growth in tumors) works against various rare solid tumors. It's a phase II study focusing on the effectiveness of these monoclonal antibodies in stopping tumor growth.

How Is the Trial Designed?

Group I: Treatment (atezolizumab, bevacizumab) Experimental Treatment 4 Interventions

Patients receive atezolizumab and bevacizumab IV over 60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

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

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, has shown significant antitumor activity, particularly in renal cell carcinoma, where it extended the time to tumor progression compared to placebo.

In advanced colorectal cancer, adding bevacizumab to chemotherapy resulted in significantly longer overall survival and progression-free survival, indicating its effectiveness when combined with standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanding the clinical development of bevacizumab. Chen, HX.[2019]

The combination of atezolizumab and bevacizumab has been shown to significantly increase overall survival in patients with advanced hepatocellular carcinoma (HCC) compared to sorafenib.

The FDA's approval of this combination therapy marks a significant advancement in the treatment of HCC, potentially changing how the disease is managed across all stages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus Bevacizumab: A Novel Breakthrough in Hepatocellular Carcinoma. Castet, F., Willoughby, CE., Haber, PK., et al.[2022]

In a multicenter study of 121 patients with advanced hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Ate/Bev), the objective response rate was 24% and the disease control rate was 76%, demonstrating real-world efficacy similar to phase III trial results.

The most common severe side effect was an increase in aspartate aminotransferase levels (10.7%), and factors like elevated baseline neutrophil-to-lymphocyte ratio were linked to poorer progression-free and overall survival, indicating the need for careful monitoring in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of atezolizumab plus bevacizumab in Korean patients with advanced hepatocellular carcinoma. Cheon, J., Yoo, C., Hong, JY., et al.[2022]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

In a combined analysis of three studies involving 490 patients, the addition of bevacizumab to FU/LV treatment resulted in a median overall survival of 17.9 months, compared to 14.6 months for the control group, indicating a significant survival benefit.

Patients receiving FU/LV with bevacizumab also experienced improved progression-free survival (8.8 months vs. 5.6 months) and a higher response rate (34.1% vs. 24.5%), demonstrating the efficacy of bevacizumab in treating metastatic colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. Kabbinavar, FF., Hambleton, J., Mass, RD., et al.[2022]

Bevacizumab (Avastin) effectively targets VEGF to inhibit tumor angiogenesis, showing a safety profile that includes mostly mild to moderate side effects such as hypertension and proteinuria, which are manageable in clinical settings.

The side effects associated with bevacizumab, including rare but serious events like gastrointestinal perforation and arterial thrombosis, do not typically exacerbate the toxicity of standard chemotherapy, making it a suitable adjunct treatment for metastatic colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing patients treated with bevacizumab combination therapy. Gordon, MS., Cunningham, D.[2015]

Bevacizumab (Avastin) has been shown to improve progression-free and overall survival in patients with various advanced cancers, including colorectal, lung, renal, breast, and ovarian cancers, based on phase III trials and real-world studies.

The safety profile of bevacizumab is well established, with manageable adverse effects such as hypertension and proteinuria, making it a valuable treatment option for patients with advanced cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab: a review of its use in advanced cancer. Keating, GM.[2022]

A total of 3120 adverse event cases related to avapritinib were reported to the FDA, with 44% occurring within the first 30 days of treatment, highlighting the importance of monitoring patients closely during this period.

The study found that elderly male patients are at a higher risk for serious adverse events, indicating that clinicians should exercise caution when prescribing avapritinib to this demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A post-marketing pharmacovigilance study of avapritinib: Adverse event data mining and analysis based on the United States Food and Drug Administration Adverse Event Reporting System database. Rong, L., Xie, M., Jiang, M., et al.[2023]

A study of 27 cancer patients with inflammatory bowel disease (IBD) showed that combining bevacizumab with chemotherapy is safe, with no observed clinical flares of IBD during treatment.

Despite some patients experiencing grade 2 or higher complications like proteinuria and hypertension, the overall safety profile suggests that bevacizumab can be effectively used in patients with either quiescent or moderately active IBD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Bevacizumab in Cancer Patients with Inflammatory Bowel Disease. Herrera-Gómez, RG., Grecea, M., Gallois, C., et al.[2022]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

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