What side effects are associated with this type of intervention?

Olaparib, a PARP inhibitor used in breast cancer treatment, commonly causes side effects such as fatigue, anemia, nausea, and vomiting. Durvalumab, a PD-L1 inhibitor, can lead to immune-related adverse events including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Both treatments may also cause general side effects like decreased appetite and diarrhea. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

Olaparib, a PARP inhibitor, has been approved by the FDA for the treatment of BRCA-mutated, HER2-negative metastatic breast cancer. This approval is based on its ability to exploit the DNA repair weaknesses in cancer cells with BRCA mutations. Durvalumab, a PD-L1 inhibitor, is part of the immune checkpoint inhibitors class, which helps to enhance the body's immune response against cancer cells. While Durvalumab itself is not specifically approved for breast cancer, other PD-1/PD-L1 inhibitors like Pembrolizumab have been approved for PD-L1 positive triple-negative breast cancer, highlighting the role of immunotherapy in this setting.

What other types of research exist?

Promising novel alternatives to Olaparib and Durvalumab for breast cancer patients include Niraparib and Talazoparib as other PARP inhibitors. For immunotherapy, Pembrolizumab (PD-1 inhibitor) and Atezolizumab (PD-L1 inhibitor) are potential alternatives. Additionally, innovative approaches such as antibody-drug conjugates and combination therapies involving PARP inhibitors with other agents like Cediranib are being explored.

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PARP Inhibitor

Radiosurgery + Olaparib + Immunotherapy for Breast Cancer Brain Metastases (SOLARA Trial)

Phase 1 & 2

Recruiting

Led By Colette Shen, M.D., Ph.D

Research Sponsored by Colette Shen

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subject has histologically confirmed diagnosis of breast cancer per AJCC 8th edition (triple negative [any BRCA status], or HER2-negative with germline or somatic BRCA mutation).

Body weight >30 kg (for durvalumab monotherapy or durvalumab combination).

Must not have

Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug.

Patients who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4:

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of focused radiation, olaparib, and immunotherapy for patients with specific types of breast cancer that have spread to the brain. The treatment aims to kill cancer cells, make them more vulnerable, and boost the body's immune response. Olaparib has shown promising results in various cancers.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include fatigue, nausea, blood count changes which could increase infection risk or cause anemia/bruising easily; allergic reactions; inflammation in organs like lungs or intestines; headaches or dizziness related to brain treatment.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My breast cancer is either triple negative or HER2-negative with a BRCA mutation.

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I weigh more than 30 kg.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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

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I have had severe blood-related side effects from my last chemotherapy that lasted more than 4 weeks.

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I have been diagnosed with a primary immunodeficiency.

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I am not taking strong or moderate drugs that affect liver enzymes.

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I do not have any serious ongoing illnesses that could affect my participation in the study.

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I have been diagnosed with myelodysplastic syndrome or acute myeloid leukemia.

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I have had cancer before, but it was a different type than my current diagnosis.

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My cancer has spread to the lining of my brain and spinal cord.

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I cannot have MRI or CT scans regularly.

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I cannot take pills by mouth or have stomach issues that affect medication absorption.

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I have signs of bleeding in my brain or risk of brain tissue shift.

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I haven't had major surgery in the last 28 days, except for brain surgery or surgery to relieve symptoms.

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I need urgent surgery for brain metastases within a week.

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My condition is rapidly worsening, affecting my internal organs.

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I have had a bone marrow or cord blood transplant in the past.

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I am not currently using, or have stopped using certain strong medications as required before starting olaparib.

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I have over 10 untreated brain tumors or their total size is larger than 15cc.

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I have a history of lung scarring or fibrosis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Frequency and severity of adverse events

Intracranial Disease control rate

Secondary study objectives

Extracranial disease progression free survival per RECIST

Extracranial disease progression free survival per iRECIST

Extracranial response rate per RECIST 1.1

+6 more

Side effects data

From 2023 Phase 3 trial • 154 Patients • NCT02184195

49%

Nausea

47%

Fatigue

38%

Diarrhoea

29%

Abdominal pain

29%

Anaemia

28%

Constipation

27%

Decreased appetite

27%

Back pain

26%

Vomiting

21%

Arthralgia

19%

Pyrexia

18%

Asthenia

13%

Rash

13%

Nasopharyngitis

11%

Alanine aminotransferase increased

11%

Dyspnoea

10%

Neuropathy peripheral

10%

Cough

10%

Abdominal pain upper

10%

Dyspepsia

10%

Anxiety

10%

Pruritus

Hyperglycaemia

Dizziness

Aspartate aminotransferase increased

Thrombocytopenia

Oedema peripheral

Pain in extremity

Insomnia

Stomatitis

Dry mouth

Headache

Neutropenia

Blood creatinine increased

Weight decreased

Dysgeusia

Blood alkaline phosphatase increased

Neutrophil count decreased

Muscle spasms

Influenza

Influenza like illness

Myalgia

Peripheral sensory neuropathy

Gamma-glutamyltransferase increased

Hypertension

Platelet count decreased

Depression

Lymphopenia

Gastrooesophageal reflux disease

Abdominal distension

Musculoskeletal pain

Flank pain

Cholangitis

Flatulence

Paraesthesia

General physical health deterioration

Bladder papilloma

Pneumonia pneumococcal

Abdominal infection

Bartholinitis

Pneumonia

Cerebrovascular accident

Pneumothorax

Gastric varices haemorrhage

Large intestinal obstruction

Cholecystitis

Anastomotic haemorrhage

Device occlusion

Stent malfunction

Bronchiolitis

Empyema

Syncope

Incisional hernia

Device dislocation

Obstruction gastric

Cardiac failure

Vascular stenosis

Pleural effusion

Incarcerated inguinal hernia

Urinary tract infection

Hypothyroidism

Transient ischaemic attack

Infusion related reaction

Duodenal perforation

Melaena

Bile duct obstruction

Pancreatitis

100%

80%

60%

40%

20%

Study treatment Arm

Olaparib 300 mg Twice Daily (bd)

Placebo

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Study Treatment ArmExperimental Treatment4 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Olaparib

2007

Completed Phase 4

~2190

Stereotactic Radiosurgery

2021

Completed Phase 2

~440

Durvalumab

2017

Completed Phase 2

~3750

0 / 21Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Olaparib, a PARP inhibitor, works by blocking the PARP enzyme involved in DNA repair, leading to the accumulation of DNA damage and cell death in cancer cells, especially those with BRCA1/2 mutations. Durvalumab, a PD-L1 inhibitor, prevents cancer cells from evading the immune system by blocking the interaction between PD-L1 on cancer cells and PD-1 on T-cells, thereby enhancing the immune response against the tumor. These targeted therapies are crucial for breast cancer patients as they offer more personalized and potentially more effective treatment options with fewer side effects compared to traditional chemotherapy.

PARP Inhibition Elicits STING-Dependent Antitumor Immunity in Brca1-Deficient Ovarian Cancer.Olaparib for the treatment of relapsed ovarian cancer with a BRCA1/2 mutation.