Atezolizumab + Bevacizumab for Rare Cancers

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

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

133 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well atezolizumab and bevacizumab work in treating patients with rare solid tumors. Immunotherapy with monoclonal antibodies, such as atezolizumab and bevacizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

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.

What data supports the effectiveness of the drug combination Atezolizumab and Bevacizumab for rare cancers?

Atezolizumab and Bevacizumab have shown effectiveness in treating advanced liver cancer, with studies indicating improved survival rates compared to other treatments. Additionally, Bevacizumab has been effective in improving survival in various advanced cancers, and Atezolizumab has shown promising results in bladder cancer, suggesting potential benefits for rare cancers as well. ^{1 2 3 4 5}

Is the combination of Atezolizumab and Bevacizumab safe for use in humans?

Atezolizumab and Bevacizumab have been studied for safety in various cancers. Bevacizumab can cause side effects like high blood pressure, protein in urine, bleeding, and wound healing issues, but these are generally manageable. Atezolizumab plus Bevacizumab has shown safety in patients with advanced liver cancer. ^{1 4 6 7 8}

How is the drug Atezolizumab + Bevacizumab unique for treating rare cancers?

Atezolizumab + Bevacizumab is unique because it combines two drugs that work together to target cancer in different ways: Atezolizumab helps the immune system attack cancer cells, while Bevacizumab blocks the blood supply that tumors need to grow. This combination has shown effectiveness in other cancers, like advanced liver cancer, and is now being explored for rare cancers where standard treatments may not exist. ^{1 4 9 10 11}

Research Team

Kanwal P. Raghav

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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.

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

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

Timeline

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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, 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

2. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of atezolizumab plus bevacizumab in Korean patients with advanced hepatocellular carcinoma. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Atezolizumab plus Bevacizumab: A Novel Breakthrough in Hepatocellular Carcinoma. [2022]

6. England 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. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Managing patients treated with bevacizumab combination therapy. [2015]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Bevacizumab in Cancer Patients with Inflammatory Bowel Disease. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Expanding the clinical development of bevacizumab. [2019]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Bevacizumab: a review of its use in combination with paclitaxel or capecitabine as first-line therapy for HER2-negative metastatic breast cancer. [2021]