Phase I Study of Olaparib and Temozolomide for Ewings Sarcoma or Rhabdoomyosarcoma

NCT01858168 | Completed Phase 1 DMC

• 1 other identifier: 13-115
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 5

Brief Summary

This research study is a Three arm Phase I clinical trial, which tests the safety of an investigational drug or combination of drugs and also tries to define the appropriate dose of the combination of investigational drugs to use for further studies. "Investigational" means that the combination of drugs is being studied. It also means that the FDA has not yet approved the combination of drugs for your type of cancer. Olaparib works by blocking the activity of a protein called poly (ADP-ribose) polymerase (PARP) which is involved in DNA repair. Cancer cells rely on PARP to repair their DNA and enable them to continue dividing. Olaparib has been used in research studies with other cancers. Information from those other research studies suggests that this drug may help to treat patients with Ewing's sarcoma. The investigational drug olaparib is not approved for any use outside of research studies. Temozolomide (Temodar) is approved by the FDA for the treatment of a type of brain tumor, glioblastoma. It has been studied in Ewing sarcoma in previous research studies. While it is not approved by the FDA for Ewing sarcoma, it is considered part of standard treatment for relapsed disease. Irinotecan is approved by the FDA for the treatment of gastrointestinal cancers. It has been studied in Ewing sarcoma in previous research studies. While it is not approved by the FDA for Ewing sarcoma, it is considered part of standard treatment for relapsed disease. Laboratory studies suggest that the combination of olaparib and temozolomide and/or irinotecan may help kill Ewing sarcoma or rhabdomyosarcoma cells. In this research study, the investigators are looking for the highest dose of the combination of olaparib and irinotecan and/or temozolomide that can be given safely. The investigators will also begin to collect information about the effects of the combination on Ewing sarcoma and rhabdomyosarcoma.

Conditions

Ewing Sarcoma; Rhabdomyosarcoma

Outcome Measures

Primary Outcomes (1)

• Determine MTD of olaparib and irinotecan and/or temozolomide

  Determine the Maximum Tolerated Dose of combine oral administration of olaparib and temozolomide.

  30 days

Secondary Outcomes (3)

• Evaluate safety and tolerability of olaparib/irinotecan and/or temozolomide combination

  2 years

• Objective response in tumor dimensions to olaparib/irinotecan and/or temozolomide

  2 years

• Explore variations in PARP activity and tumor characteristics

  2 years

Study Arms (3)

One

EXPERIMENTAL

Olaparib, taken orally twice per day on days 1-7 (week 1) of each cycle Temozolomide, taken orally once per day on days 1-7 (week 1) of each cycle for patients with Ewing sarcoma

Drug: Olaparib; Drug: Temozolomide

Two

EXPERIMENTAL

Olaparib, taken orally twice per day on days 1-7 (week 1) of each cycle Temozolomide, taken orally once per day on days 1-7 (week 1) of each cycle Irinotecan, given by IV once per day on days 1-7 of each cycle

Drug: Olaparib; Drug: Temozolomide; Drug: Irinotecan

Three

EXPERIMENTAL

Olaparib, taken orally twice per day on days 1-7 (week 1) of each cycle Temozolomide, taken orally once per day on days 1-7 (week 1) of each cycle for patients with Rhabdomyosarcoma

Drug: Olaparib; Drug: Temozolomide

Interventions

Olaparib DRUG

Tablets to be taken on an empty stomach twice a day.

Also known as: AZD2281

One; Three; Two

Temozolomide DRUG

Tablets to be taken on an empty stomach before bedtime.

Also known as: Temodal, SCH52365, Temodar

One; Three; Two

Irinotecan DRUG

Administered via IV

Also known as: Camptosar

Two

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed Ewing's sarcoma
• Ewing's sarcoma must have progressed following at least one standard prior chemotherapy regimen
• Life expectancy of at least 16 weeks
• Willing to comply with the protocol for the duration of the study including pre- and post-treatment biopsies, undergoing treatment, scheduled visits and examinations including follow up
• Presence of measurable disease
• Prior approval from insurance company to obtain oral temozolomide for the duration of the study

You may not qualify if:

• Involvement in the planning and/or conduct of the study
• Previous enrollment in the present study
• Participation in another clinical study with an investigational product during the 21 days prior to first dose of olaparib and temozolomide
• Receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study treatment
• Concurrent use of the following classes of inhibitors of CYP3A4: azole antifungals, macrolide antibiotics, protease inhibitors
• Persistent clinically significant toxicities caused by previous cancer therapy
• Previously documented diagnosis of myelodysplastic syndrome (or any dysplastic leukocyte morphology suggestive of MDS) or acute myeloid leukemia
• Symptomatic uncontrolled brain metastases
• Major surgery within 14 days of starting study treatment
• Considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection
• Unable to swallow orally administered medication and subjects with gastrointestinal disorders likely to interfere with absorption of study medication
• Pregnant or breastfeeding
• Known to be serologically positive for HIV and receiving antiviral therapy
• Subjects with known active hepatitis B or C
• Known hypersensitivity to olaparib or any of the excipients of the product

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (5)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

St. Jude's Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

MeSH Terms

Conditions

Sarcoma, Ewing; Rhabdomyosarcoma

Interventions

olaparib; Temozolomide; Irinotecan

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids

Study Officials

• Edwin Choy, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prinicipal Investigator

Study Record Dates

• First Submitted: May 8, 2013
• First Posted: May 21, 2013
• Study Start: July 1, 2013
• Primary Completion: November 1, 2024
• Study Completion: December 12, 2025
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)