Olaparib for Pediatric Cancer

Recruiting at31 trial locations

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: AstraZeneca

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the idea that Olaparib for Pediatric Cancer is an effective treatment?

The available research shows that Olaparib, also known as Lynparza, is primarily used for treating adult cancers like breast and ovarian cancer, especially in patients with specific genetic mutations. There is no direct data provided on its effectiveness for pediatric cancer. However, its success in treating other cancers, such as ovarian cancer, where it has shown promising results in patients with certain genetic backgrounds, suggests potential for effectiveness in similar genetic conditions. Without specific data on pediatric cancer, it's difficult to make a direct comparison to other treatments for this age group. ^{1 2 3 4 5}

What safety data exists for Olaparib (Lynparza) treatment?

Olaparib (Lynparza) has been evaluated for safety in various studies. It is generally well tolerated, with most adverse events being mild to moderate. Severe adverse events include fatigue, anemia, and neutropenia. Safety data comes from trials in patients with ovarian cancer, breast cancer, and other solid tumors, including a Phase I study in Japanese patients with advanced solid tumors. ^{2 3 5 6 7}

Is the drug Olaparib (Lynparza) a promising treatment for pediatric cancer?

Olaparib (Lynparza) is a promising drug because it has shown effectiveness in treating certain types of adult cancers, like breast and ovarian cancer, especially in patients with specific genetic mutations. This suggests it could be valuable for treating other cancers, potentially including pediatric cancer. ^{1 3 4 5 7}

Research Team

Milenkova Tsveta

Principal Investigator

AstraZeneca

Eligibility Criteria

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 am between 6 months and 18 years old.

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.

Treatment Details

Interventions

• Olaparib (PARP Inhibitor)

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.

Participant Groups

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.

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

Findings from Research

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]

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 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, 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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of olaparib for treating ovarian cancer. [2015]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Olaparib: first global approval. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

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

5. England 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. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Safety and tolerability of the olaparib tablet formulation in Japanese patients with advanced solid tumours. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

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