Radiosurgery + Olaparib + Immunotherapy for Breast Cancer Brain Metastases

(SOLARA Trial)

Recruiting at 6 trial locations

Overseen By Allison Lipps

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Colette Shen

Must be taking: Olaparib

Must not be taking: Strong CYP3A inhibitors, Strong CYP3A inducers

Disqualifiers: Leptomeningeal carcinomatosis, Brain injury, Autoimmune disorders, others

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

Compensation: Varies

Number of Visits: Unknown

41 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with breast cancer that has spread to the brain. Researchers study the safety and effectiveness of focused radiation (radiosurgery) combined with the cancer drug olaparib, followed by immunotherapy using durvalumab. The trial targets patients with specific types of breast cancer, either triple-negative or BRCA-mutated, who have noticeable brain metastases. Suitable candidates for this trial include those with this type of cancer who have at least one brain metastasis larger than 5mm and plans for focused radiation treatment. As a Phase 1, Phase 2 trial, the research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires a washout period for certain medications. If you are taking strong or moderate CYP3A inhibitors or inducers, you will need to stop them 2 to 5 weeks before starting olaparib. Other medications may also need to be stopped, so it's best to discuss your current medications with the trial team.

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

Research has shown that olaparib, a drug used in this trial, is usually well-tolerated. Common side effects include nausea and low red blood cell count (anemia), but only 6.3% of patients discontinued use due to these issues. Importantly, recent studies have not identified any new safety concerns.

Stereotactic radiosurgery, the focused radiation treatment in this trial, also appears safe. Studies indicate it is effective and safe for treating cancer that has spread to the brain from breast cancer.

Lastly, durvalumab, an immunotherapy drug in this study, is considered safe for many cancer patients. It has a manageable safety profile when used with other treatments.

Overall, previous research shows that the treatments in this trial are generally safe. However, like all treatments, they may still cause side effects in some patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this combination treatment for breast cancer brain metastases because it brings together olaparib, a PARP inhibitor, and stereotactic radiosurgery (SRS) with immunotherapy in a novel way. Unlike traditional treatments like chemotherapy or whole-brain radiation, which can affect healthy tissue, SRS precisely targets tumor sites, potentially reducing side effects. Olaparib specifically exploits cancer cell weaknesses by interfering with DNA repair, making it a powerful partner to radiosurgery. Additionally, the inclusion of durvalumab, an immunotherapy drug, could enhance the immune system's ability to fight cancer, offering a multi-pronged attack against the disease that current standard treatments don't provide.

What evidence suggests that this trial's treatments could be effective for breast cancer brain metastases?

Research shows that olaparib, which participants in this trial will receive, may effectively treat breast cancer with certain genetic changes. Studies found that it helped patients live longer without disease progression compared to some traditional chemotherapy treatments. Stereotactic radiosurgery (SRS), also part of this trial, is a precise form of radiation therapy that effectively controls cancer spread to the brain, with success rates between 65% and 94% for breast cancer cases. Regarding immunotherapy, durvalumab, another treatment in this trial, demonstrated lasting tumor shrinkage in treating advanced triple-negative breast cancer. Together, these treatments offer potential hope for managing breast cancer that has spread to the brain. ^{4 6 7 8 9}

Who Is on the Research Team?

Colette Shen

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

This trial is for adults over 18 with breast cancer that has spread to the brain, specifically triple negative or BRCA-mutated types. They should have completed prior cancer treatments at least a week before and recovered from any acute effects except hair loss. Participants need normal organ and bone marrow function, must not be pregnant, agree to use contraception, and have a life expectancy of more than 16 weeks.

Inclusion Criteria

I may have cancer spread beyond the brain without immediate life-threatening symptoms.

I am willing to follow the safe sex or abstinence guidelines for 3 months after treatment.

I have new brain metastasis and am planning to undergo or have undergone specific brain radiation treatments.

Exclusion Criteria

I haven't had extensive radiation to my bone marrow or wide field radiation in the last 4 weeks.

I have or had an autoimmune or inflammatory disorder.

I have previously received treatments targeting PD-1, PD-L1, or CTLA-4.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation and Olaparib Treatment

Cycle 1: Olaparib is given twice daily concurrently with stereotactic radiosurgery (SRS) for up to 28 days

4 weeks

Systemic Therapy and Durvalumab

Cycle 2 and 3: Physician's choice systemic therapy and durvalumab are administered, each cycle lasting 21 days

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Olaparib
• Physicians Choice Systemic Chemotherapy
• Stereotactic Radiosurgery

Trial Overview The study tests focused radiation therapy combined with olaparib (a drug), followed by immunotherapy durvalumab in patients with brain metastases from certain breast cancers. It includes an initial phase where different doses of olaparib are tested alongside radiosurgery, then systemic chemotherapy chosen by the physician plus durvalumab.

How Is the Trial Designed?

Group I: Study Treatment Arm Experimental Treatment 4 Interventions

Cycle 1 of study treatment will consist of Olaparib twice daily concurrently with stereotactic radiosurgery (SRS). Olaparib will start one week prior to SRS and continue during and following SRS (1-5 fractions) for up to 28 days total. Once the subject has recovered from SRS, Cycle 2 will be initiated with physician's choice systemic therapy and durvalumab. Cycle 2+ will equal 21 days. During Cycles 2 and 3, physician's choice systemic monotherapy will be given along with durvalumab. Each cycle will last 21 days. Imaging to evaluate intracranial and extracranial disease will be performed after Cycle 3, and subjects with response will continue with the systemic therapy and durvalumab until progression (intracranial or extracranial), unacceptable toxicity or death.

Olaparib is already approved in European Union, United States for the following indications:

Approved in European Union as Lynparza for:

• Breast cancer
• Ovarian cancer
• Fallopian tube cancer
• Peritoneal cancer
• Pancreatic cancer
• Prostate cancer
• Endometrial cancer

Approved in United States as Lynparza for:

• Ovarian, fallopian tube, and primary peritoneal cancer
• Breast cancer
• Prostate cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

Colette Shen

Lead Sponsor

Trials

1

Recruited

40+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

University of North Carolina, Chapel Hill

Collaborator

Trials

1,588

Recruited

4,364,000+

Published Research Related to This Trial

In a study of 106 patients with early-stage non-small cell lung cancer treated with CyberKnife® SBRT, the treatment demonstrated an 88% local control rate at 2 years, indicating its efficacy in managing this type of cancer.

The treatment was associated with low toxicity, with only 20% of patients experiencing mild fatigue and 17% mild dyspnea, and only 4% experiencing significant late effects, suggesting it is a safe option for medically inoperable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk-adapted robotic stereotactic body radiation therapy for inoperable early-stage non-small-cell lung cancer. Temming, S., Kocher, M., Stoelben, E., et al.[2022]

In a study of 251 patients with 1-4 brain metastases, linac-based stereotactic radiosurgery (SRS) did not show a significant reduction in the incidence of symptomatic radionecrosis compared to a multi-source gamma-ray system, with rates of 3.8% for linac and 9.3% for gamma-ray (p=0.43).

Both treatment methods resulted in similar local control rates and overall survival, but linac-based SRS had a significantly shorter treatment delivery time (approximately 3.1 minutes) compared to the gamma-ray system (approximately 49 minutes).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosurgery of limited brain metastases from primary solid tumor: results of the randomized phase III trial (NCT02355613) comparing treatments executed with a specialized or a C-arm linac-based platform. Scorsetti, M., Navarria, P., Cozzi, L., et al.[2023]

Out of 221 reported incidents related to CyberKnife™ SRS and SBRT from 2012 to 2019, the majority (205 incidents) had little to no clinical impact, indicating a high level of safety in the treatment process.

Human performance issues were the most common contributing factor (79% of incidents), with many errors occurring during pre-treatment phases, highlighting the need for improved training and protocols to enhance patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Common Error Pathways in CyberKnife™ Radiation Therapy. Mullins, BT., Mazur, L., Dance, M., et al.[2020]

In a study involving 95 patients with 134 lung metastases, Cyberknife stereotactic radiosurgery demonstrated a high local control rate of 97.6% at one year and 87.0% at three years, indicating its efficacy in treating lung metastases.

The treatment was found to be safe, with no severe toxicity (grade 4 or higher) reported, suggesting that Cyberknife is a tolerable option for patients with oligometastatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes of cyberknife stereotactic radiosurgery for lung metastases. Wang, Z., Kong, QT., Li, J., et al.[2022]

Moderately dosed stereotactic radiosurgery (SRS) for one to four brain metastases showed a median overall survival of 7.5 months, with high local brain control rates of 87% at 6 months and 79% at 12 months, indicating its efficacy in treating limited brain metastases.

The study suggests that initial SRS alone can be a safe treatment option, as only 22% of patients required additional whole-brain radiotherapy, and significant predictors of survival included the time between the primary diagnosis and brain metastases, as well as the volume of the treated metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of moderately dosed radiosurgery for limited brain metastases. Report of a single-center experience. Meisner, J., Meyer, A., Polivka, B., et al.[2021]

Stereotactic radiosurgery for brain metastases from breast cancer showed a high tumor control rate of 93% and a median survival of 13 months post-treatment, indicating its efficacy as a treatment option.

The absence of multiple brain metastases was the only significant factor associated with longer survival, while the treatment had a low complication rate, with only a few cases of radiation-induced edema that did not require further surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery for brain metastases from breast cancer. Firlik, KS., Kondziolka, D., Flickinger, JC., et al.[2019]

Stereotactic radiosurgery is an effective and noninvasive treatment for brain metastases, providing ablative doses of radiation for long-term control of macroscopic disease, especially in patients with a limited number of metastases.

While there is mature data supporting the use of stereotactic radiosurgery in combination with whole-brain radiation therapy, more prospective randomized studies are needed to clarify its effectiveness in patients with multiple metastases and in various treatment settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Radiosurgery for Treatment of Brain Metastases. Badiyan, SN., Regine, WF., Mehta, M.[2018]

Stereotactic radiosurgery is a valuable treatment option for both intracranial and extracranial lesions, often used alongside surgery, conventional radiation, and chemotherapy.

The review highlights the evolution and variety of stereotactic radiosurgery machines, including the Gamma Knife, indicating a growing range of technologies available for effective cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delivery of stereotactic radiosurgery: a cross-platform comparison. Nguyen, T., Hsu, W., Lim, M., et al.[2011]

In a study of 18 breast cancer patients with spinal metastases treated with CyberKnife radiosurgery, outcomes were comparable to 18 matched patients who received conventional external beam radiotherapy, indicating that CyberKnife can be an effective salvage treatment option.

While survival rates and complications did not show significant differences between the CyberKnife and conventional treatment groups, the CyberKnife treatment did not result in added toxicity, suggesting it is a safe alternative for patients with limited options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyberknife radiosurgery for breast cancer spine metastases: a matched-pair analysis. Gagnon, GJ., Henderson, FC., Gehan, EA., et al.[2007]

A recent meta-analysis suggests that patients with brain metastases may have better survival outcomes when treated with stereotactic radiosurgery alone, rather than in combination with whole-brain radiation therapy, although this finding may be influenced by differences in patient characteristics.

The American Society of Radiation Oncology has recommended against the routine use of whole-brain radiation therapy alongside stereotactic radiosurgery, leading to controversy among radiation oncologists who still support the effectiveness of whole-brain radiation therapy based on existing evidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole-brain radiation therapy for brain metastases: detrimental or beneficial? Gemici, C., Yaprak, G.[2018]

Stereotactic radiosurgery (SRS) using CyberKnife is a safe and effective treatment for elderly patients (≥65 years) with brain metastases, achieving high local control rates and maintaining a stable quality of life in 97.9% of patients.

In a study of 97 patients, SRS demonstrated a 79% overall survival rate at 3 months and a 99.2% local tumor progression-free rate at 6 months, indicating its efficacy compared to traditional whole brain radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of CyberKnife radiosurgery in elderly patients with brain metastases: a retrospective clinical evaluation. Acker, G., Hashemi, SM., Fuellhase, J., et al.[2021]

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