16 Participants Needed

Olaparib for Pediatric Cancer

Recruiting at 31 trial locations
AC
Overseen ByAstraZeneca Clinical Study Information Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 2 JurisdictionsThis treatment is already approved in other countries

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.12345

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.13567

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.12346

Research Team

MT

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.
See 5 more

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.
See 5 more

Timeline

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

Treatment Details

Interventions

  • Olaparib
Trial OverviewThe 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
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
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

Find a Clinic Near You

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 (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.
New Adjuvant Treatment for High-Risk Early Breast Cancer.Aschenbrenner, DS.[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.
Safety evaluation of olaparib for treating ovarian cancer.Lheureux, S., Bowering, V., Karakasis, K., et al.[2015]
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.
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]

References

New Adjuvant Treatment for High-Risk Early Breast Cancer. [2022]
Safety evaluation of olaparib for treating ovarian cancer. [2015]
Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. [2022]
Olaparib: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian cancer. [2016]
Olaparib: first global approval. [2020]
Olaparib: a review of its use as maintenance therapy in patients with ovarian cancer. [2016]
Safety and tolerability of the olaparib tablet formulation in Japanese patients with advanced solid tumours. [2022]