A Phase 2 interventional study of Olaparib in Advanced Malignant Solid Neoplasm, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma and Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma, sponsored by National Cancer Institute (NCI). Completed at 113 sites in 2 countries. Open to participants aged 12 Months to 21 Years. Per ClinicalTrials.gov, last updated 2024-12-11.
Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment
This phase II Pediatric MATCH trial studies how well olaparib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with defects in deoxyribonucleic acid (DNA) damage repair genes that have spread to other places in the body (advanced) and have come back (relapsed) or do not respond to treatment (refractory). Olaparib is an inhibitor of PARP, an enzyme that helps repair DNA when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy.
PRIMARY OBJECTIVE:
I. To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with olaparib with advanced solid tumors (including central nervous system [CNS] tumors), non-Hodgkin lymphomas or histiocytic disorders that harbor activating genetic alterations in the deleterious genetic alterations in the DNA damage repair (DDR) pathway.
SECONDARY OBJECTIVES:
I. To estimate the progression free survival in pediatric patients treated with olaparib with advanced solid tumors including non-Hodgkin lymphomas, CNS tumors, and histiocytosis that harbor deleterious genetic alterations in the DDR pathway.
II. To obtain information about the tolerability of olaparib in children and adolescents with relapsed or refractory cancer.
III. To provide preliminary estimates of the pharmacokinetics of olaparib in children and adolescents with relapsed or refractory cancer.
EXPLORATORY OBJECTIVE:
I. To explore approaches to profiling changes in tumor genomics over time through the evaluation of circulating tumor DNA.
OUTLINE:
Patients receive olaparib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
Patients must have radiographically measurable disease at the time of study enrollment; patients with neuroblastoma who do not have measurable disease but have iobenguane (MIBG) positive (+) evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) and visible on more than one slice
Note: The following do not qualify as measurable disease:
Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =\< 16 years of age
Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
Stem cell infusions (with or without total body irradiation [TBI]):
Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
A serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
Exclusion Criteria:
Concomitant medications
Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
Drug: Olaparib
Given PO
Also known as: AZD 2281, AZD-2281, AZD2281, KU 0059436, KU-0059436, KU0059436, Lynparza, Olanib, Olaparix, PARP Inhibitor AZD2281
Objective Response Rate (Complete Response/Partial Response)
A responder is defined as a patient who achieves a best response of partial response or complete response on the study. Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed using the Wilson score interval method. The revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to determine response and progression in this study, with specific criteria outlined for the different subtypes of tumors (e.g., 2-dimensional measurements for central nervous system (CNS) tumors).
Time frame: Up to 2 years from study entry
Progression Free Survival (PFS)
The Kaplan-Meier method will be used to estimate the 6 month PFS. PFS is defined as time from initiation of protocol treatment to disease progression, recurrence, death from any cause, or date of last contact.
Time frame: Up to 6 months from study entry
Percentage of Patients Experiencing Treatment-related Grade 3 or Higher Adverse Events
Percentage of patients experiencing treatment-related grade 3 or higher adverse events will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Time frame: Up to 2 years from study entry
Pharmacokinetics (PK) of Olaparib, Area Under the Curve (AUC)
The mean (sd) of the AUC.
Time frame: Up to day 8 of cycle 1
Change in Tumor Genomic Profile
Approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid will be explored. Descriptive analysis will be performed and will be summarized with simple summary statistics.
Time frame: Cycle 5 day 1 to 4 years
| Milestone | Treatment (Olaparib) |
|---|---|
| Started | 6 |
| Completed | 0 |
| Not completed | 6 |
| Withdrew: Adverse event | 1 |
| Withdrew: Death | 1 |
| Withdrew: Withdrawal by subject | 1 |
| Withdrew: Progressive disease | 3 |
A responder is defined as a patient who achieves a best response of partial response or complete response on the study. Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed using the Wilson score interval method. The revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to determine response and progression in this study, with specific criteria outlined for the different subtypes of tumors (e.g., 2-dimensional measurements for central nervous system (CNS) tumors).
| percentage of participants | Treatment (Olaparib) |
|---|---|
| Objective Response Rate (Complete Response/Partial Response) | 0 (0 to 0) |
The Kaplan-Meier method will be used to estimate the 6 month PFS. PFS is defined as time from initiation of protocol treatment to disease progression, recurrence, death from any cause, or date of last contact.
| percentage of participants | Treatment (Olaparib) |
|---|---|
| Progression Free Survival (PFS) | 33.3 (4.6 to 67.6) |
Percentage of patients experiencing treatment-related grade 3 or higher adverse events will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
| percentage of participants | Treatment (Olaparib) |
|---|---|
| Percentage of Patients Experiencing Treatment-related Grade 3 or Higher Adverse Events | 16.7 (0.4 to 64.1) |
The mean (sd) of the AUC.
| mcg*hr/ml | Treatment (Olaparib) |
|---|---|
| Pharmacokinetics (PK) of Olaparib, Area Under the Curve (AUC) | 48.8 ± 27.8 |
Approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid will be explored. Descriptive analysis will be performed and will be summarized with simple summary statistics.
Results for this outcome have not been posted.
Collected over Adverse Events monitored/assessed from enrollment to 30 days after the end of treatment, up to 2 years. All-Cause Mortality monitored/assessed up to 5 years. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment (Olaparib) | 4/6 (66.7%) | 3/6 (50%) | 5/6 (83.3%) |
| Event | Treatment (Olaparib) |
|---|---|
| Disease progressionGeneral disorders | 1/6 |
| Allergic reactionImmune system disorders | 1/6 |
| HypercalcemiaMetabolism and nutrition disorders | 1/6 |
| SeizureNervous system disorders | 1/6 |
| Event | Treatment (Olaparib) |
|---|---|
| Lymphocyte count decreasedInvestigations | 4/6 |
| AnemiaBlood and lymphatic system disorders | 3/6 |
| NauseaGastrointestinal disorders | 3/6 |
| White blood cell decreasedInvestigations | 3/6 |
| VomitingGastrointestinal disorders | 2/6 |
| DizzinessNervous system disorders | 2/6 |
| HeadacheNervous system disorders | 2/6 |
| HypertensionVascular disorders | 2/6 |
| Cardiac disorders - Other, specifyCardiac disorders | 1/6 |
| Sinus tachycardiaCardiac disorders | 1/6 |
| Age, Categorical(Participants) | Treatment (Olaparib) |
|---|---|
| <=18 years | 5 |
| Between 18 and 65 years | 1 |
| >=65 years | 0 |
| Age, Continuous(years) | Treatment (Olaparib) |
|---|---|
| Mean | 14.5 ± 4.4 |
| Sex: Female, Male(Participants) | Treatment (Olaparib) |
|---|---|
| Female | 2 |
| Male | 4 |
| Ethnicity (NIH/OMB)(Participants) | Treatment (Olaparib) |
|---|---|
| Hispanic or Latino | 3 |
| Not Hispanic or Latino | 3 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Treatment (Olaparib) |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 4 |
| More than one race | 0 |
| Unknown or Not Reported | 1 |
| Region of Enrollment(participants) | Treatment (Olaparib) |
|---|---|
| United States | 6 |
Showing the first 100 of 113 sites across 2 countries.
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National Cancer Institute (NCI)