What side effects are associated with this type of intervention?

Common treatments for solid tumors, particularly those involving PARP inhibitors like Olaparib, often have side effects such as nausea, fatigue, anemia, and gastrointestinal disturbances (e.g., diarrhea, constipation). Other systemic therapies, including chemotherapy and targeted agents, can cause myelosuppression, neuropathy, alopecia, mucosal inflammation, hypertension, and cardiovascular effects. The severity and type of side effects can vary based on the specific agent and patient factors.

What prior FDA approvals exist?

Olaparib, a PARP inhibitor, has been approved by the FDA for the treatment of advanced cancers with BRCA1/2 mutations, including ovarian and breast cancers. Other PARP inhibitors like niraparib and rucaparib have also shown efficacy in treating solid tumors, particularly in ovarian cancer. Niraparib has demonstrated progression-free survival benefits in maintenance therapy for advanced ovarian cancer, while rucaparib has been used in recurrent ovarian carcinoma after response to platinum therapy. These approvals highlight the role of PARP inhibitors in targeting homologous recombination deficiencies in solid tumors.

What other types of research exist?

Promising alternatives to Olaparib for solid tumor patients include Niraparib and Rucaparib, both of which have shown efficacy in various cancers. Additionally, combination therapies such as Abiraterone plus Niraparib or Abiraterone plus Olaparib have demonstrated improved outcomes in specific patient subgroups. Emerging therapies like Adavosertib (a WEE1 inhibitor) combined with chemotherapy and novel antibody-drug conjugates are also being explored and show potential.

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PARP Inhibitor

Olaparib for Pediatric Cancer

Q: What is the mechanism of action of this treatment?

The most common treatments for solid tumors include chemotherapy, targeted therapy, and immunotherapy. Chemotherapy works by killing rapidly dividing cells, but it can also affect healthy cells, leading to side effects. Targeted therapies, such as PARP inhibitors like Olaparib, specifically target cancer cells with certain genetic mutations, such as BRCA1/2, by inhibiting the PARP enzyme involved in DNA repair, leading to cancer cell death. Immunotherapy boosts the body's immune system to recognize and destroy cancer cells. These mechanisms are crucial for solid tumor patients as they offer more personalized and potentially more effective treatment options with fewer side effects compared to traditional chemotherapy.

Phase 1

Recruiting

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

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

Must have

A formalin fixed, paraffin embedded (FFPE) tumour sample from the primary cancer (all patients) suitable for central HRR testing and a blood sample (patients ≥2 years old) for central germline BRCA testing must be provided for each patient

For all non-neuroblastoma tumours, patients must have at least 1 radiographical assessable lesion (measurable and/or non-measurable). For neuroblastoma tumours, patients must have radiographical assessable disease with at least 1 lesion (measurable and/or non measurable) OR disease evidenced by uptake of meta-iodobenzylguanidine- (MIBG) or fluorodeoxyglucose positron emission tomography (FDG-PET) scans

Must not have

Concomitant use of known strong or moderate CYP3A inhibitors or concomitant use of known strong or moderate CYP3A inducers

Previous treatment with a PARP inhibitor, including olaparib

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 64 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing olaparib, a medication, to see if it is safe for children and teenagers with certain hard-to-treat tumors. These patients have tumors that have come back or haven't responded to other treatments. Olaparib works by stopping cancer cells from fixing themselves, which can help to kill them. Olaparib has been approved for use in various cancers, including ovarian and breast cancer, and has shown promising activity in both adult and pediatric patients.

Who is the study for?

This trial is for children and adolescents aged 6 months to under 18 with solid tumors that have relapsed or are resistant to treatment. They must be able to swallow tablets, have a tumor sample available for testing, and meet specific genetic criteria indicating a deficiency in HRR (a DNA repair process). Patients who've had certain recent treatments or those with blood disorders like MDS/AML can't participate.

What is being tested?

The study tests the safety and tolerability of Olaparib, a medication targeting cancer cells' DNA repair mechanisms. It's given to young patients with solid tumors. The trial has two phases: dose finding for all eligible patients and signal identification specifically for those with confirmed HRR gene mutations.

What are the potential side effects?

While not explicitly listed here, common side effects of Olaparib may include nausea, fatigue, anemia (low red blood cell counts), vomiting, diarrhea, decreased appetite, headache, coughing and shortness of breath.

Eligibility Criteria

Inclusion Criteria

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

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I can provide a tumor sample and, if I'm over 2, a blood sample for testing.

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My cancer can be seen and measured on scans.

Exclusion Criteria

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

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I am not taking any strong or moderate drugs that affect enzyme CYP3A.

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I have been treated with a PARP inhibitor like olaparib before.

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I have been diagnosed with MDS/AML or have symptoms suggesting it.

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I cannot swallow pills.

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I still have side effects from past cancer treatments.

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I do not have untreated brain or spinal issues related to my cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 64 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 64 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 64 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Dose limiting toxicity [DLTs]

Safety profile

Secondary study objectives

Apparent total clearance of the drug from plasma at steady state after oral administration [CLss/F]

Area under the curve at 0-8 hours [AUC(0-8)]

Area under the curve at steady state [AUCss]

+9 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

4Treatment groups

Experimental Treatment

Group I: Signal identificationExperimental Treatment1 Intervention

A secondary analysis of response in patients recruited into the signal identification phase will be conducted. Patients included in this analysis must have documented evidence of a deleterious or suspected deleterious germline or tumour HRR gene mutation. A minimum of 10 patients across age and dose cohorts with deleterious or suspected deleterious HRR mutations will be enrolled.

Group II: Cohort C: ≥6 months to <6 yearsExperimental Treatment1 Intervention

Patients will receive a single dose of olaparib on Day 1, followed by initiation of bd continuous dosing from Day 2 onwards. Olaparib should be taken at the same time each day (morning and evening), approximately 12 hours apart. Patients in Cohort C will receive a predetermined number of each sprinkle capsule strength (15 and 19.5 mg,) to make up the required dose. Olaparib sprinkle capsules will be administered to the child by the parent/caregiver. Patients in Cohort C are not required to fast including PK sampling days. The dispensed granules should be swallowed whole and not chewed, crushed, dissolved or divided, and should be consumed within 30 minutes of preparation.

Group III: Cohort B: ≥3 to <12 yearsExperimental Treatment1 Intervention

Patients will receive a single dose of olaparib on Day 1, followed by initiation of bd continuous dosing from Day 2 onwards. Olaparib tablets should be taken at the same time each day (morning and evening), approximately 12 hours apart with one glass of water. The tablets should be swallowed whole and not chewed, crushed, dissolved or divided. Olaparib tablets can be taken with or without food, with the exception of Day 8 (a PK sampling day) when patients aged ≥3 years old receiving tablets should take olaparib at least 1 hour after food and should refrain from eating for up to 2 hours afterwards.

Group IV: Cohort A: ≥12 to <18 yearsExperimental Treatment1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Olaparib

2007

Completed Phase 4

~2190

0 / 8Eligibility 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

The most common treatments for solid tumors include chemotherapy, targeted therapy, and immunotherapy. Chemotherapy works by killing rapidly dividing cells, but it can also affect healthy cells, leading to side effects. Targeted therapies, such as PARP inhibitors like Olaparib, specifically target cancer cells with certain genetic mutations, such as BRCA1/2, by inhibiting the PARP enzyme involved in DNA repair, leading to cancer cell death. Immunotherapy boosts the body's immune system to recognize and destroy cancer cells. These mechanisms are crucial for solid tumor patients as they offer more personalized and potentially more effective treatment options with fewer side effects compared to traditional chemotherapy.