Olaparib With Ceralasertib in Recurrent Osteosarcoma

NCT04417062 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 20-086
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Osteosarcoma; Osteosarcoma Recurrent

Keywords

Osteosarcoma; Osteosarcoma Recurrent

Outcome Measures

Primary Outcomes (2)

• Cohort 1 Event Free at 4 months

  Simon's two-stage design will be applied to the primary (binary) endpoint, event-free at 4-months. An event is defined as the occurrence of relapse, disease progression as defined by RECIST 1.1, or death from any cause.

  4 months after start of protocol therapy

• Cohort 2 paired pre-/post-treatment tumor Assessment

  Estimate the proportion of patients who have paired pre-/post-treatment tumor samples adequate for biomarker studies and / or derivation of PDX models.

  4 months after start of protocol therapy

Secondary Outcomes (5)

• Objective Response Rate

  2 years

• Event Free Survival

  time from registration to the earlier of progression, relapse, or death due to any cause up to 4 years

• Overall Survival

  From registration until death from any cause up to 4 years

• Cohort 2 Event Free Survival 12 months

  12 months

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0

  enrollment until 30 days after last dose of study treatment up to 24 Months

Study Arms (1)

Olaparib-Ceralasertib

EXPERIMENTAL

Unresectable disease (can not be surgically removed) will be enrolled into Cohort 1 and Resectable disease (can be surgically removed) which is limited only to the lung parenchyma will be enrolled into Cohort 2. * Olaparib at a predetermined dose orally 2 times a day on days 1-28 * Ceralasertib will be given at a predetermined dose orally 2 times a day on days 1-14 in 28-day study cycles. Patients can remain on treatment for up to 2 years if disease progression has not occurred.

Drug: Olaparib; Drug: Ceralasertib

Interventions

Olaparib DRUG

Olaparib is taken by mouth, twice daily through out the 28 day study cycle.

Also known as: Lynparza

Olaparib-Ceralasertib

Ceralasertib DRUG

Ceralasertib is taken by mouth, twice daily on days 1-14 of the study cycle.

Also known as: AZD6738

Olaparib-Ceralasertib

Eligibility Criteria

• Age: 12 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Osteosarcoma Institute: collaborator
• AstraZeneca: collaborator

Study Sites (4)

UCSF Benioff Children's Hospital; UCSF Pediatrics Hematology Oncology

San Francisco, California, 94158, United States

Location

Dana Farber Cancer Institite

Boston, Massachusetts, 02115, United States

Location

Memorial Sloan Kettering

New York, New York, 10065, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Osteosarcoma

Interventions

olaparib; ceralasertib

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Study Officials

• Katherine Janeway, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 2, 2020
• First Posted: June 4, 2020
• Study Start: November 24, 2020
• Primary Completion: June 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (4)