Olaparib With Ceralasertib in Recurrent Osteosarcoma

Running, not enrolling · Phase 2

Conditions studied: Osteosarcoma, Osteosarcoma Recurrent

In brief

This study is being done in order to evaluate the effectiveness of using two drugs (olaparib and ceralasertib) to treat patients with osteosarcoma that has not responded to treatment or has come back after treatment The names of the study drugs involved in this study are: * Olaparib * Ceralasertib

Key facts

Study ID

NCT04417062

Run by

Dana-Farber Cancer Institute

People needed

63

Starts

2020-11-24

Expected to finish

2026-06-01

Last updated by the study team

2026-02-25

Who can join

Age: 12 and older, up to 40. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Provision of informed consent prior to any study specific procedures.
• Age > 12 years and ≤ 40 years
• Weight > 40 kg
• Lansky/Karnofsky performance status ≥ 60% for participants ≥16 years of age and Lansky ≥ 60% for participants <16 years of age (see Appendix B) within 28 days prior to enrollment with no deterioration over the previous 2 weeks. Please note, patients who have had prior orthopedic surgery as part of their osteosarcoma therapy should not be considered non-ambulatory in their performance status if their non-ambulatory status is the result of surgery.
• Estimated life expectancy of ≥16 weeks.
• Diagnosis requirement
• All participants must have histologic verification of osteosarcoma at original diagnosis or relapse
• All participants must have disease that has relapsed or has become refractory to conventional therapy
• Cohort 1 Requirements
• Participants must have measurable disease according to RECIST v1.1. At least one measurable lesion that can be accurately assessed at baseline by computed tomography (CT) (magnetic resonance imaging [MRI] where CT is contraindicated) and is suitable for repeated assessment as per RECIST v1.1.
• Surgical resection of all possible sites of disease is not feasible or will result in major and / or unacceptable morbidity and no other standard of care treatment is available per assessment of the treating investigator
• Participants must have archival tumor specimen available for submission.
• Cohort 2 Requirements
• Participants must have had at least one episode of disease recurrence currently limited to the lung parenchyma with no limits on the number of episodes of recurrence
• Surgical resection of all possible sites of suspected pulmonary metastases in order to achieve a complete remission is considered feasible by treating physicians
• Participants with pulmonary disease on only one side must have archival tumor specimen available for submission.
• Participants must have fully recovered from the acute toxic effects of all prior anti-cancer therapy. Participants must meet the following minimum washout periods prior to registration:
• Myeloid growth factors: At least 14 days following the last dose of long-acting growth factor (e.g. Neulasta) or 7 days following short-acting growth factor.
• Stem Cell or Autologous T Cell Infusion: At least 42 days must have elapsed after stem cell or autologous T cell infusion.
• Participants must not have previously received and progressed on olaparib or other PARP inhibitor therapy.
• Participants must not have previously received and progressed on ceralasertib or other ATR inhibitor therapy.
• Participants must have normal organ function as defined below.
• Bone Marrow Function
• Absolute neutrophil count ≥1,250/uL
• Platelets ≥100,000/uL (with no platelet transfusions within the last 28 days)

You may not qualify if…

• Participants with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) or features suggestive of MDS/AML.
• Patients with a known diagnosis of ataxia telangiectasia.
• Cytotoxic chemotherapy, hormonal or non-hormonal targeted therapy within 21 days of Cycle 1 Day 1 is not permitted (a duration of five half times is allowed for patients treated with noncytotoxic drugs).
• Immunotherapy within 42 days of Cycle 1 Day 1.
• Prior TOTAL lung radiation. If prior radiation included lung then radiation must have been completed 12 weeks before Cycle 1 Day 1 AND V20 (% of lung that received 20Gy) must not exceed 25% OR the mean lung dose must be less than 5Gy. Even if these eligibility criteria are met, patients who have received prior radiotherapy including lung are only eligible after review and approval by the study PI.
• Palliative radiotherapy to sites not including lung must have been completed 7 or more days before Cycle 1 Day 1 (with the following exception: patients receiving radiation to more than 30% of the bone marrow or with a wide field of radiation must have been completed 4 weeks before C1D1. The patient can receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study as long as these were started at least 5 days prior to the study treatment.
• Receiving, or having received during the 14 days prior to Cycle 1 Day 1, corticosteroids (at a dose > 10 mg prednisone/day or equivalent) for any reason. Topical, inhaled or ophthalmic steroid administration is acceptable.
• Major surgery within 2 weeks of starting study treatment: patients must have recovered from any effects of any major surgery.
• Any other malignancy which has been active or treated within the past three years, with the exception of cervical intra-epithelial neoplasia and non-melanoma skin cancer, Ductal Carcinoma in Situ, stage 1 grade 1 endometrial carcinoma, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years prior to study entry.
• With the exception of alopecia and CTCAE grade 2 neuropathy, any unresolved toxicities from prior therapy ≥ Common Terminology Criteria for Adverse Events (CTCAE) grade 2.
• Patient with resting left-ventricular ejection fraction (LVEF) < 50% measured by ECHO/MUGA
• Any of the following cardiac diseases currently or within the last 6 months (by New York Heart Association (NYHA) ≥ Class 2 where applicable):
• Unstable angina pectoris
• Congestive heart failure or known reduced LVEF < 50%
• Acute myocardial infarction
• Conduction abnormality not controlled with pacemaker or medication e.g. complete left bundle branch block, third degree heart block
• Significant ventricular or supraventricular arrhythmias e.g. (patients with chronic rate controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible)
• Patients at risk of brain perfusion problems, e.g., medical history of carotid stenosis or pre-syncopal or syncopal episodes, history of TIAs
• Uncontrolled hypertension (grade 2 or above) requiring clinical intervention
• Corrected QT interval (QTc) > 470msec obtained from 3 electrocardiograms (ECGs) 2-5 minutes apart using the Fredericia formula
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as congestive heart failure, unstable angina pectoris, acute myocardial infarction, hypokalaemia, congenital long QT syndrome, immediate family history of long QT syndrome or unexplained sudden death under 40 years of age, conduction abnormality not controlled with pacemaker or medication.
• Patients with relative hypotension (less than 5th percentile for age/height/sex or systolic and/or diastolic blood pressure >15% below baseline) or clinically relevant orthostatic hypotension (a fall in systolic blood pressure of at least 20 mm Hg within 3 minutes of standing compared to blood pressure obtained from sitting/supine position).
• Concomitant use of known potent cytochrome P (CYP) 3A inhibitors (eg.itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study treatment is five half-lives.
• Concomitant use of known potent (eg. phenobarbital, enzalutamide, phenytoin, rifampicin,rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) CYP3A inducers (eg.bosentan, efavirenz, modafinil). The required washout period prior to starting study treatment is five half-lives, except for St-Johns' wort, which is 3 weeks.
• Patient has had prescription or non-prescription drugs or other products known to be CYP3A4 and/or CYP2B6 substrates or CYP3A4 and/or CYP2B6 substrates with a narrow therapeutic index. Exposure of other drugs metabolised by CYP3A4 and/or CYP2B6 may be reduced and additional monitoring may be required The use of herbal supplements or 'folk remedies' (and medications and foods that significantly modulate CYP3A activity) should be discouraged. If deemed necessary, such products may be administered with caution and the reason for use documented in the CRF. Please see Appendix E for further details.

Where it is running

• UCSF Benioff Children's Hospital; UCSF Pediatrics Hematology Oncology — San Francisco, California, United States
• Dana Farber Cancer Institite — Boston, Massachusetts, United States
• Memorial Sloan Kettering — New York, New York, United States
• MD Anderson — Houston, Texas, United States

Full record on ClinicalTrials.gov

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