Bevacizumab + Doxorubicin + Radiation for Sarcoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Massachusetts General Hospital

Must not be taking: Anticoagulants, Anthracyclines

Disqualifiers: Metastatic disease, Pregnancy, others

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

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

Compensation: Varies

Number of Visits: 2

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for certain types of sarcoma, a cancer that begins in the body's connective tissues. Researchers aim to determine the safety and effectiveness of combining bevacizumab (Avastin) with doxorubicin (a common chemotherapy drug) and radiation therapy. The goal is to find better treatments for sarcomas that may recur after surgery or spread to other parts of the body. Suitable participants have a soft tissue sarcoma that hasn't spread and have not previously received radiation. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Do I have to stop taking my current medications for the trial?

The trial requires that you have not received chemotherapy, immunotherapy, or radiotherapy within 4 weeks before starting the study drugs. If you are currently on these treatments, you will need to stop them before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining bevacizumab and doxorubicin with radiation therapy has been studied for safety and effectiveness. In one study, adding bevacizumab improved patient response to treatment and extended survival, although the study did not specifically focus on sarcoma. This suggests the combination might be tolerable, but further research is needed.

Some patients have tolerated bevacizumab well when used with doxorubicin. However, bevacizumab can cause side effects like high blood pressure and an increased risk of bleeding. Doxorubicin may lead to heart-related side effects, especially at higher doses or with long-term use.

Radiation therapy is generally safe, but it can cause tiredness and skin changes in the treated area. Researchers continue to test how to safely and effectively combine these treatments. Since this study is in an early phase, it primarily focuses on safety and determining the right dose, so much remains to be learned about how well patients handle this treatment combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Bevacizumab, Doxorubicin, and Radiation Therapy for treating sarcoma because this approach targets the cancer in a multi-faceted way. Bevacizumab works by inhibiting the blood vessels that supply nutrients to the tumor, essentially starving it, while Doxorubicin is a chemotherapy agent that attacks cancer cells directly via a different mechanism. Adding Radiation Therapy helps to further damage the cancer cells and prevent their growth. This combination could potentially enhance the effectiveness of treatment compared to using these therapies individually or the current standard treatments, which typically rely on surgery, radiation, and chemotherapy used separately.

What evidence suggests that this treatment might be an effective treatment for sarcoma?

Research has shown that combining bevacizumab with doxorubicin and radiation therapy may help treat certain cancers. In this trial, participants will receive this combination treatment. One study found that adding bevacizumab improved patient response to treatment and extended survival by about 4.7 months. Another study reported that 65% of patients maintained stable disease, meaning their cancer did not worsen. Additionally, a different study found that half of the patients experienced a significant reduction in tumor size with a similar treatment combination. These results suggest this treatment could be effective, but further research is needed to confirm these findings for sarcomas. ^{3 6 7 8 9}

Who Is on the Research Team?

Edwin Choy, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults with intermediate- or high-grade soft tissue sarcoma that can be surgically removed, located on limbs, trunk, or pelvis. The tumor must be at least 5 cm across or a local recurrence of any size without prior radiation. It's not for those with metastatic disease, pregnant/breastfeeding individuals, recent major surgery patients, people who have had doxorubicin/anthracycline chemotherapy/bevacizumab before, or those with certain medical conditions.

Inclusion Criteria

My cancer is a primary or locally recurrent soft tissue sarcoma and I haven't had radiation before.

My primary tumor is at least 5 cm wide or I have a local recurrence of any size.

My sarcoma is confirmed to be of intermediate or high severity.

Exclusion Criteria

I have not had a heart attack or any heart procedures in the last 6 months.

I have not had major surgery in the last 4 weeks.

I have a condition that makes my blood clot more than normal.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive bevacizumab, metronomic doxorubicin, and radiation therapy

6 weeks

Weekly visits for drug administration and radiation therapy

Surgery

Surgical evaluation and potential removal of the tumor

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

Annual follow-up calls

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Doxorubicin
• Radiation Therapy

Trial Overview The study tests the safety and effectiveness of combining bevacizumab (a drug not yet approved for sarcomas) with doxorubicin chemotherapy and radiation therapy to find the maximum tolerated dose. As a Phase I clinical trial, it focuses on determining the right dosage for further research.

How Is the Trial Designed?

Group I: Treatment Arm Experimental Treatment 3 Interventions

Bevacizumab, metronomic doxorubicin and radiation therapy

Bevacizumab is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2005.16.139

Phase II Study of Doxorubicin and Bevacizumab for ... The addition of bevacizumab demonstrated increased response rate, time to progression, and a 4.7 month increase in overall survival, leading to ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/16192597/

Phase II study of doxorubicin and bevacizumab for patients ... The 12% response rate for these patients was no greater than that observed for single-agent doxorubicin. However, the 65% of patients with stable disease ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00356031

Bevacizumab and Radiation Therapy for Sarcomas The main purpose of this study is to test the effectiveness of bevacizumab in combination with radiation therapy to see what effects (good or bad) they have ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301610009557

Phase II Study of Neoadjuvant Bevacizumab and ... In that study, 50% of the patients showed major or complete pathologic responses (≥80% tumor necrosis).

5. academic.oup.com academic.oup.com/jnci/article/106/11/dju329/1500708

Combining Targeted Agents With Modern Radiotherapy in ... The NRG oncology sarcoma working group is currently designing a prospective randomized trial to evaluate this highly precise radiation technique ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01746238?tab=history&a=19

Bevacizumab/​Doxorubicin/​Radiation for Sarcoma Outcome Measures · Pathologic response rate · gene expression signatures · Obtain preliminary data overall survival · Microvessel density · Obtain preliminary data ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7693687/

Radiation Therapy in Adult Soft Tissue Sarcoma—Current ... With a median f/u of 12 months, they observed 1-year local control and overall survival rates of 88% and 61%, which is superior to the published ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2452109422001282

Safety and Tolerability of Metastasis-Directed Radiation ... The aim of this review was to describe up-to-date published data on the safety and tolerability of metastasis-directed hypofractionated radiation therapy (RT)

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4994894/

A Feasibility Study of Bevacizumab Plus Dose-Dense ... The primary objective was to determine the cardiac safety of adjuvant bevacizumab administered for 1 year (concurrently with dose-dense doxorubicin– ...