Atezolizumab + Chemotherapy for Thyroid Cancer

Overseen By Maria E. Cabanillas, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Corticosteroids, Anti-PD-1, Anti-PD-L1, others

Disqualifiers: Autoimmune disease, Liver disease, HIV, 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: 21

Duration: Up to 5 years

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of atezolizumab and chemotherapy in patients with aggressive thyroid cancer. The treatment aims to boost the immune system and stop cancer cell growth. Atezolizumab helps enhance the immune response against cancer cells.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, the use of corticosteroids is not allowed for 10 days before starting atezolizumab, except for certain cases like physiological replacement. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Atezolizumab in combination with chemotherapy for thyroid cancer?

Atezolizumab, when combined with nab-paclitaxel, has shown effectiveness in treating advanced triple-negative breast cancer by significantly prolonging progression-free survival compared to placebo, as seen in the IMpassion130 trial. This suggests potential benefits when used in combination with chemotherapy for other cancers, although specific data for thyroid cancer is not available. ^{1 2 3 4 5}

Is the combination of Atezolizumab and Chemotherapy safe for humans?

Atezolizumab, when combined with nab-paclitaxel (a type of chemotherapy), has been used in treating advanced breast cancer and has shown a safety profile consistent with each drug individually. Common side effects include fatigue, nausea, and immune-related issues like rash and thyroid problems. Serious side effects, though less common, can include anemia and liver inflammation. ^{1 3 6 7 8}

How is the drug combination of Atezolizumab and Paclitaxel unique for treating thyroid cancer?

The combination of Atezolizumab, an immune checkpoint inhibitor, and Paclitaxel, a chemotherapy drug, is unique because it leverages the immune system to target cancer cells, which is different from traditional chemotherapy that directly attacks cancer cells. This approach has shown promise in other cancers like triple-negative breast cancer, suggesting potential benefits for thyroid cancer, which lacks standard treatment options. ^{1 2 3 9 10}

Research Team

Maria E. Cabanillas, M.D.

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with anaplastic or poorly differentiated thyroid cancer that can't be removed by surgery or has spread. They must have proper kidney and liver function, not be pregnant, agree to use contraception, and have no autoimmune diseases. People who've had certain previous cancer treatments or have serious heart conditions, uncontrolled hypertension, active hepatitis or HIV are excluded.

Inclusion Criteria

I can perform all self-care but cannot work.

Ability to provide informed consent

I have a measurable thyroid cancer lesion, unless I have anaplastic thyroid cancer.

Exclusion Criteria

I do not have eye conditions that exclude me from cohorts 1 and 2.

I do not have a history of serious heart problems, including specific heart rhythm issues.

You have HIV, active hepatitis B, or hepatitis C infections. If you had hepatitis B in the past, you can join the study, but you will need to be watched closely by a specialist. If you have hepatitis C antibodies, you can join only if a specific test is negative.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atezolizumab in combination with chemotherapy based on cohort assignment. Treatment cycles repeat every 21 or 28 days depending on the cohort.

Up to 5 years

Visits every 21 or 28 days for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 3 months for the first 2 years, every 6 months for years 3-4, and then yearly thereafter.

5 years

Regular follow-up visits as per schedule

Treatment Details

Interventions

• Atezolizumab
• Bevacizumab
• Cobimetinib
• Nab-paclitaxel
• Paclitaxel
• Vemurafenib

Trial Overview The study tests if atezolizumab combined with chemotherapy (paclitaxel, nab-paclitaxel) and targeted drugs (vemurafenib, cobimetinib) improves outcomes in thyroid cancer compared to standard treatments. It examines how well these drugs work together to stop cancer growth by targeting specific enzymes and boosting the immune system's response.

Participant Groups

Group I: Cohort IV (nab-paclitaxel, atezolizumab, paclitaxel,) Experimental Treatment 3 Interventions

Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15 and atezolizumab IV on day 1 over 30-60 minutes. Patients may receive paclitaxel IV over 30 minutes on day 1 as a substitute for nab-paclitaxel. Cycles repeat every 21 days in the absence of disease progression and unacceptable toxicity.

Group II: Cohort III (atezolizumab, bevacizumab) Experimental Treatment 2 Interventions

Patients receive atezolizumab IV over 30-60 minutes and bevacizumab IV over 60-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression and unacceptable toxicity.

Group III: Cohort II (atezolizumab, cobimetinib) Experimental Treatment 2 Interventions

Patients receive cobimetinib PO QD on days 1-21 and atezolizumab IV over 30-60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression and unacceptable toxicity.

Group IV: Cohort I (vemurafenib, cobimetinib, atezolizumab) Experimental Treatment 3 Interventions

Patients receive vemurafenib PO BID on days 1-21, cobimetinib PO QD on days 1-21, and atezolizumab IV over 30-60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression and 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

Atezolizumab, combined with nab-paclitaxel, significantly improved progression-free survival in patients with advanced triple-negative breast cancer (TNBC) compared to placebo, based on the phase III IMpassion130 trial involving patients with unresectable locally advanced or metastatic TNBC.

While the combination therapy showed a tolerable safety profile, with common side effects like neutropenia and immune-related adverse events, it did not significantly affect health-related quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab (in Combination with Nab-Paclitaxel): A Review in Advanced Triple-Negative Breast Cancer. Kang, C., Syed, YY.[2020]

The ANTELOPE trial is a phase II study comparing the efficacy of a pemetrexed-free regimen (atezolizumab, carboplatin, and nab-paclitaxel) against a pemetrexed-based regimen (pembrolizumab, cis-/carboplatin, and pemetrexed) in treating TTF-1 negative non-small cell lung adenocarcinoma (NSCLC/ADC).

This trial aims to enroll 136 participants across 30 sites in Germany, focusing on overall survival as the primary endpoint, which will help determine the best treatment approach for this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design of the Phase II ANTELOPE Study of Atezolizumab, Carboplatin and nab-Paclitaxel vs. Pembrolizumab, Platinum and Pemetrexed in TTF-1 Negative, Metastatic Lung Adenocarcinoma (AIO-TRK-0122). Frost, N., Bleckmann, A., Griesinger, F., et al.[2023]

Atezolizumab combined with nab-paclitaxel has been approved by the FDA for treating patients with locally advanced or metastatic triple-negative breast cancer that expresses PD-L1.

This combination therapy is significant as it is the first immunotherapy regimen to receive marketing authorization for any form of breast cancer, marking a new treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab Combo Approved for PD-L1-positive TNBC. [2020]

Atezolizumab, when used with nab-paclitaxel for treating triple negative breast cancer, can cause rare side effects like autoimmune hemolytic anemia, as seen in a case study of a 59-year-old female patient.

The patient's hemolytic anemia was effectively managed with a high-dose prednisone taper, allowing her to continue her cancer treatment without further complications through multiple cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab-induced hemolytic anemia - A case report. Younce, CM., Lawton, JM., Patel, DR.[2021]

Atezolizumab significantly improves overall survival in patients with metastatic non-small cell lung cancer (mNSCLC), with median survival times of 13.8 months in the atezolizumab group compared to 9.6 months in the docetaxel group in the OAK trial.

The treatment has an acceptable safety profile, with common side effects including fatigue and decreased appetite, and serious immune-related adverse events occurring in a small percentage of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. Weinstock, C., Khozin, S., Suzman, D., et al.[2022]

Atezolizumab, a PD-L1 blocking antibody, shows higher rates of objective response, progression-free survival, and overall survival when used as a first-line therapy in chemotherapy-naïve patients with metastatic non-small cell lung cancer (NSCLC), compared to its use in later treatment lines.

The review included 15 ongoing studies, with 5 reporting results, indicating that atezolizumab is being explored in various treatment combinations and settings, suggesting its potential as a versatile first-line treatment option for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for the First-Line Treatment of Non-small Cell Lung Cancer (NSCLC): Current Status and Future Prospects. Ryu, R., Ward, KE.[2023]

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]

References

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

Atezolizumab (in Combination with Nab-Paclitaxel): A Review in Advanced Triple-Negative Breast Cancer. [2020]

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

Rationale and Design of the Phase II ANTELOPE Study of Atezolizumab, Carboplatin and nab-Paclitaxel vs. Pembrolizumab, Platinum and Pemetrexed in TTF-1 Negative, Metastatic Lung Adenocarcinoma (AIO-TRK-0122). [2023]

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

FDA Approval Summary: Atezolizumab Plus Paclitaxel Protein-bound for the Treatment of Patients with Advanced or Metastatic TNBC Whose Tumors Express PD-L1. [2021]

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

Atezolizumab Combo Approved for PD-L1-positive TNBC. [2020]

5. Ireland pubmed.ncbi.nlm.nih.gov

Atezolizumab in patients with advanced non-small cell lung cancer and history of asymptomatic, treated brain metastases: Exploratory analyses of the phase III OAK study. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Atezolizumab-induced hemolytic anemia - A case report. [2021]

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

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Phase 1b/2a study of trastuzumab emtansine (T-DM1), paclitaxel, and pertuzumab in HER2-positive metastatic breast cancer. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Atezolizumab for the First-Line Treatment of Non-small Cell Lung Cancer (NSCLC): Current Status and Future Prospects. [2023]

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

Atezolizumab: First Global Approval. [2019]