1. SARC 005: Adjuvant treatment of high risk uterine LMS with gemcitabine/docetaxel followed by doxorubicin: a phase II multi-center trial
PI: Martee L. Hensley, MD

2. Objectives:
Determine 2-year PFS among women with uterine LMS treated with gem-doce, followed by doxorubicin
Determine tolerability/toxicity
Explore predictors of PFS: age, tumor size, grade, serosal involvement, STS stage v. FIGO stage, mitotic rate, ER, PR, menopausal status at dx

3. Schema Gemcitabine 900 mg/m2 over 90 minutes days 1, 8
Docetaxel 75 mg/m2 day 8
q 3 wk x 4 cycles
Repeat CT scan
Doxorubicin 60 mg/m2 q 3 w x 4
Repeat CT scan within 6 weeks after
CT c/a/p every 3 mo for 2 y, then every 6 mo

4. Eligibility No other cancer within 5 years No prior gem, doce, or dox
FIGO stage I or II, high grade LMS s/p hysterectomy (uterine-limited disease with pathology showing serosal involvement IS eligible even though this is FIGO IIIA)
<12 weeks from surgery
NED by CT within 3 weeks of enrollment
Good marrow, kidneys, liver
No other cancer within 5 years
No prior gem, doce, or dox
No prior pelvic RT
No current HRT or anti-hormone therapy
EF > 50%

5. Correlative studies
Provide tumor details: size, serosal disease, mitotic rate
Provide patient details: age, menopausal status at dx and at start of adjuvant therapy
Send unstained slides to MSKCC
- ER and PR
- Site paid $75 when slides are received

6. Statistical issues Target accrual 45 patients
Bayesian model for continuous assessment of PFS and safety
Accrue at least 15 patients per year
Stop early if data suggest 2 year PFS will be no better than 30%

7. Minimum total patient-days
Calculating futility
Event: death or evidence of progression
Stop if number of events is too many for the total patient-disease-free-days-on study:
Number of events
Minimum total patient-days 1 2 3
408 4
920 5
1435 6
1955 7
2477 8
3003

8. Data capture and management
On line SARC registration
On line data entry
On line CRFs—easy to use
- All grade 3 and 4
- Selected grade 2 (neurological,
hypersensitivity, pulmonary)
Data monitored by SARC
Some detail for management plan after recurrence
Vital status after recurrence every 6 months

9. Milestones
Full protocol written, reviewed, approved by SARC, industry sponsors
Contracts between SARC and Lilly, SARC and Sanofi-Aventis are completed
Gemcitabine and docetaxel both supplied
Drug distribution from SARC via Biologics to institutions

10. Milestones Protocol IRB-approved, contracts, etc: MSKCC, WCI, DFCI
Several recent IRB approvals, contracts pending: U Mich, Penn, Moffitt

11. Results First accrual: 13 February 2006 Accrual to date: 7 - MSKCC 5
- Univ Wash 2
Events = 0
3 patients have completed all planned therapy
Progression-free days = 1063

12. Results: toxicity Grade 3 heme tox: 1 patient
No pulmonary toxicity
No patients off study for toxicity

13. For discussion: Any barriers to opening study?
Any accrual difficulties?
Any unexpected treatment difficulties?

14. Next steps:
Treatment likely to be safe, deliverable as adjuvant, sequential therapy
Assuming the 2-year PFS is as targeted, SARC should start to design the phase III trial
Major issue: “Control” arm that is reasonable and accruable
Pelvic RT? (would likely appeal to Gyn Onc/GOG)
Observation? (would be hard to accrue)
Short-term biologic? (no good rationale)
Short-term single agent chemo? (not a real control, and might wash out any difference)