Olaparib for Pediatric Cancer

No longer recruiting at 32 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: AstraZeneca

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: MDS/AML, Unresolved toxicity, Untreated CNS disease, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 28 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if olaparib is safe and tolerable for children and teens with solid tumors that have returned or resist treatment. Researchers are testing olaparib, an experimental medication, in different age groups to evaluate its performance. Eligible participants have a solid tumor or primary central nervous system tumor with a specific genetic issue (HRR deficiency) and have exhausted standard treatment options. 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 treatment.

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

The trial requires that you do not use strong or moderate CYP3A inhibitors or inducers while participating. If you are taking these, you may need to stop. The protocol does not specify other medications, but you should discuss with the trial team.

Is there any evidence suggesting that olaparib is likely to be safe for children and adolescents?

Research has shown that olaparib has been promising in earlier studies with children. In these studies, most children tolerated the medication well. Some children with specific DNA issues in their tumors even responded positively. However, possible serious side effects should be noted. These can include bone marrow problems, such as Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML), which affect blood cell production. Although olaparib is approved for adults with certain cancers, its safety and effectiveness in children remain under investigation. While some evidence suggests children can tolerate it, further research is needed to confirm its safety for them. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Olaparib is unique because it targets cancer by inhibiting PARP, an enzyme involved in DNA repair. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, olaparib specifically targets cancer cells with defective DNA repair mechanisms. This precision reduces damage to healthy cells, potentially leading to fewer side effects. Additionally, olaparib's oral administration offers convenience compared to intravenous options, making it a more appealing choice for pediatric patients and their caregivers. Researchers are excited about this targeted approach as it represents a shift towards more personalized and less toxic cancer therapies.

What evidence suggests that olaparib might be an effective treatment for pediatric cancer?

Research has shown that olaparib might help treat solid tumors in children. In a previous study, olaparib was generally well tolerated and helped shrink tumors in 2 out of 15 patients, indicating possible benefits. Early results suggest the drug can reduce DNA damage in about half of the patients. While olaparib already treats other cancers like ovarian cancer, its success there offers hope for treating children's cancers. This trial will evaluate olaparib in different pediatric age groups, targeting specific gene changes that allow cancer cells to repair themselves, potentially stopping tumor growth. ^{2 6 7 8 9}

Who Is on the Research Team?

Milenkova Tsveta

Principal Investigator

AstraZeneca

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

My cancer has returned or is not responding to treatment, and it lacks certain repair genes.

For dose finding phase only: recruitment will be open to all patients with HRR deficiency, based on a local test. For the signal identification phase: recruitment will be open only to patients with documented evidence of a deleterious or suspected deleterious germline or tumour HRR gene mutation that meets the AZ HRR rules

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

Exclusion Criteria

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

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

I haven't had cancer radiotherapy (except for comfort care) or any approved cancer drugs in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olaparib monotherapy with a single dose on Day 1, followed by continuous dosing from Day 2 onwards

28 days

Daily dosing with specific PK sampling on Day 8 and Day 28

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Signal Identification

Secondary analysis of response in patients with HRR gene mutations

Up to 64 months

What Are the Treatments Tested in This Trial?

Interventions

• Olaparib

Trial Overview

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.

How Is the Trial Designed?

Group I: Signal identification Experimental Treatment 1 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 years Experimental Treatment 1 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 years Experimental Treatment 1 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 years Experimental Treatment 1 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.

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?

AstraZeneca

Lead 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

Published Research Related to This Trial

Olaparib is an effective treatment for patients with platinum-sensitive, relapsed BRCA-mutated high-grade serous ovarian cancer, showing significant improvement in progression-free survival compared to placebo in a study of 265 patients.

The treatment is generally well tolerated, with most side effects being mild to moderate, although fatigue, anemia, and neutropenia were noted as more severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: a review of its use as maintenance therapy in patients with ovarian cancer. Frampton, JE.[2016]

Olaparib is a powerful inhibitor of PARP-1 and PARP-2, showing effectiveness in treating ovarian cancer, particularly in patients with germline BRCA mutations.

Phase III trials are currently evaluating olaparib's efficacy as a maintenance therapy after initial treatment in patients with BRCA mutations, highlighting its potential role in long-term cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian cancer. Gunderson, CC., Moore, KN.[2016]

Olaparib (Lynparza) is approved for treating adult patients with high-risk early breast cancer that has a germline BRCA mutation, following chemotherapy treatment.

This approval highlights Olaparib's role as an adjuvant therapy, which means it is used after initial treatments to help prevent cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Treatment for High-Risk Early Breast Cancer. Aschenbrenner, DS.[2022]

Olaparib, a PARP inhibitor, showed a 36% objective response rate in women with relapsed ovarian cancer and a germline BRCA1/2 mutation, even after they had undergone multiple lines of chemotherapy, indicating its efficacy in this challenging patient population.

The median duration of response to olaparib was 7.4 months, and the safety profile was consistent across patients who had received three or more lines of prior chemotherapy, with similar rates of serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Matulonis, UA., Penson, RT., Domchek, SM., et al.[2022]

In a Phase I study involving 28 Japanese patients with advanced solid tumors, olaparib tablets at doses of 200 and 300 mg twice daily were found to be tolerable, with no dose-limiting toxicities reported.

The most common side effects included nausea, decreased appetite, anemia, and constipation, but no confirmed antitumor responses were observed, leading to the selection of 300 mg bid as the recommended dose for future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of the olaparib tablet formulation in Japanese patients with advanced solid tumours. Yonemori, K., Tamura, K., Kodaira, M., et al.[2022]

Olaparib is an effective oral treatment for patients with BRCA mutation-positive ovarian cancer, approved for maintenance therapy after platinum-based chemotherapy, showing good tolerability with common side effects like nausea, fatigue, and anemia being mild to moderate.

Long-term monitoring is recommended due to a low risk of serious hematological complications, such as anemia and myelodysplastic syndrome, ensuring patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of olaparib for treating ovarian cancer. Lheureux, S., Bowering, V., Karakasis, K., et al.[2015]

Olaparib is an oral medication that inhibits poly (ADP-ribose) polymerase and is primarily developed for treating BRCA mutation-positive ovarian cancer, with its capsule formulation already approved in the EU and USA.

The drug is currently undergoing extensive clinical trials for various cancers, including breast, gastric, and pancreatic cancers, indicating its potential broad application in oncology beyond ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: first global approval. Deeks, ED.[2020]

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