PI: Martee L. Hensley, MD
description
Transcript of PI: Martee L. Hensley, MD
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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
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Objectives:
• Determine 2-year PFS among women with uterine LMS treated with gem-doce x 4, followed by doxorubicin x 4
• 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
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SchemaGemcitabine 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
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Eligibility
• > 18 years• FIGO stage I or II, high grade
LMS s/p hysterectomy (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%
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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
-institutions are paid $75 when slides are received
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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%
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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 time on test in days
1 0
2 0
3 408
4 920
5 1435
6 1955
7 2477
8 3003
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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 (neuro, hypersensitivity,
pulmonary)• Data monitored by SARC• Some detail for management plan after recurrence• Vital status after recurrence every 6 months
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Drug details
• Gemcitabine and docetaxel both supplied
• Drug distribution from SARC via Biologics to institutions
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Open Sites
• MSKCC• Washington Cancer
Institute• U Michigan• Dana Farber• U Chicago
• Penn Onc/Hem• Moffitt• St. Vincent’s• Mass General• MedStar• MDACC
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Results
First accrual: 2/13/06
• Accrual to date: 22 patients
• Recurrence/Death events = 0
• 9 patients have completed all planned therapy
• Progression-free days = 5211 (as of 28 Sep 07)
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Results—are we on target?
• Target accrual goal 15 patients per year: in 19. months we have 22—seems okay
• Treatment is highly unlikely to be futile: up to 7 events could have happened in 2477 days and we have had 0 events in over 5700 days
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Results: toxicity
Gr 3 G/T heme 4 pts (6 events)Gr 3 Dox heme 6 pts (11 events)Gr 4 Dox heme 3 pts (3 events)Gr 2 G/T hypersensitivity 3 pts (3 events)Gr 3 G/T hypersensitivity 1 patient (1
event)
No pulmonary toxicity1 patient off study treatment for abnl AST/ALT after C3 G/T—
proceeded on to doxorubicin. Remains on study for f/u purposes
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For discussion:
• Clarify in next amendment that patients that must discontinue Gem-Doce for toxicity reasons may remain on study treatment to complete the doxorubicin
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Discussion of next steps:
• Is a phase III trial with a no-chemotherapy control arm accruable?
• Scientifically reasonable control arm options are:– Pelvic RT (would likely appeal to Gyn Onc/GOG)– Observation (could be hard to accrue)
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Phase III size considerations:
• Home run assumption: 50% PFS at 2 y for “no chemo” group (arm B) and 80% PFS at 2 y for “chemo” group (arm A).
-two sided 0.05 level calculation with continuity correctionsType I error Power N for arm A or arm B Total N for two arms
0.05 0.80 46 92 0.05 0.85 51 102 0.05 0.90 58 116
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Phase III size considerations:
• Chemo improves PFS by 30% assumption: 50% PFS at 2 y for “no chemo” group (arm B) and 65% PFS at 2 y for “chemo” group (arm A).
-two sided 0.05 level calculation with continuity correctionsType I error Power N for arm A or arm B Total N for two arms
0.05 0.80 183 366 0.05 0.85 297 414 0.05 0.90 240 480
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Are there other options?:
• Increase the sample size of SARC 005 in order to narrow the confidence interval?
• Open the eligibility to non-uterine LMS (which will of course increase heterogeneity)?
• Even if we put our hearts and time behind a phase III, funding for such large trial may be very challenging