Transcript Objectives of this Phase 1 trial Study Design

Phase I Study of Olaparib and Temozolomide,
in patients with recurrent and/or metastatic
Ewing sarcoma : An Interim Update
Edwin Choy, Gregory Cote, James
Butrynski, David Harmon, Suzanne
George, Andrew Wagner, Jeffrey Morgan,
David D’Adamo, George Demetri
Olaparib/EWS-FlI1
interaction is one of
the strongest
associations among
639 cell lines and
130 drugs screened
Olaparib prevents EWS-FLI1-positive xenograft growth and metastasis.
Single Agent Olaparib is Not Effective in Ewing Sarcoma
Choy et al. BMC Cancer. In Press
Single Agent Olaparib is Not Effective in Ewing Sarcoma
Choy et al. BMC Cancer. In Press
Olaparib synergizes with TMZ in EWS-FLI1-positive xenograft mice
Objectives of this Phase 1 trial
Study Design:
Phase I 3+3 dose escalation study of olaparib
and temozolomide in patients with recurrent
and/or metastatic Ewing’s sarcoma.
Treatment regimen:
Olaparib is administered orally with
temozolomide on an outpatient basis, given
for 7 days every 21 days.
Imaging:
CT/MRI prior to starting study drug, after 6
and 12 weeks from starting study drug, and
every 9 weeks thereafter. Additional scans
may be performed as clinically indicated.
Subjects will continue to be followed until
disease progression or death.
Inclusion Criteria:
•Histologically-confirmed Ewing’s sarcoma.
•Measurable disease on cross sectional imaging of
at least 1cm
•ECOG performance status 0-2
•Life expectancy >3 months
•Age ≥ 18 years.
•Patients must have received at least one line of
chemotherapy, including adjuvant therapy, for
the initial treatment of Ewing’s sarcoma. There will
be no limits on number of prior regimens using
chemotherapy or investigational agents.
•Allowed for prior treatment with temozolomide
Dose Levels
Attributable AEs
Best Response by RECIST 1.1
*
*
*
*
*
* Received prior TMD
*
*
*
# of DLTs per Dose Level
Dose Level
DLTs
1
0/3
2
0/3
3
0/3
4
0/3
5
2/2
Conclusions
• We designed and conducted a phase I clinical trial to
administer olaparib and temozolomide in patients with
Ewing sarcoma progressing after prior chemotherapy
• 5 dose levels were tested
• minor responses were seen in 6 of 14 evaluable
patients
• MTD was surpassed at dose level 5
• Dose expansion study will be performed using olaparib
at 200 mg BID and temozolomide at 75 mg/m2 QD.
Acknowledgments
Mentorship
•George Demetri, DFCI
•Daniel Haber, MGH
•Jose Baselga, MGH
•Jane Robertson, Astra Zeneca
Clinical Trials Unit at DFCI and MGH
•Coauthors
•Kristina Goodman
•Barbara Anderson
•David Wells
•Eleanor Saffian
•Basyl Stuyvesant
•Melissa Hohos
•Mark Morley
•Julie Field
•Sarah Solomon
Funds
•Ludwig Center at Dana-Farber / Harvard Cancer Center
•Jennifer Hunter Yates Sarcoma Foundation
•Brian MacIsaac Sarcoma Fund