Use of a natural history phase for the design of trials for duchenne muscular dystrophy (DMD)

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82 Abstracts easily and cheaply measured and with ~mportant and val,dated prognostic lntormatlon The use of randomized trials to prove the merits of such an attitude and to allow therapeutzc progress leads one to build prognostic classifications Within a prognostic class, one compares. with appropriate sample sizes, all or only a subset ot the treatments but adlacent prognostic classes receive at h_'ast one common treatment We have, set up two cooperative randomized studies of this kind (chronic lymphocytic leukemia, melanoma) Use of a Natural History Phase for the Design of Trials for Duchenne Muscular Dystrophy (DMD) Collaboratwe Investlgatxon ot Duchenne Dystrophy Group, Washington Umvcrs;ty, St Louts, Mtssourt (P52) A collaborative study ot DMD included a one-year natural h~story phase to chart the disease progression in boys of varying ages Since no single oblect~ve measurement provided an acceptable parameter tot the evaluation of therapeutic ethcacy, a variety ot laboratory meas- urements, functional gradmgs, and ratings of muscle strength and range ot motion data were collected for 100 patients on 8 visits spaced over a one-year interval lntra- and mterpatlent differences were evaluated in order to prowde tmal design parameters An a~erage ot muscle strength evaluations at each time pemod proved to be particularly attrachve because ot ~ts reproducibflltyand hneanty wzth age The measurements over time allowed us toexaluatethe ~atlhty of extended basehne periods m order to establish lndiwdual rates ot progression ot DMD This natural history phase also allowed tor the estimation of the expected changes in the parameters over time tacihtatmg sample s~ze calculations tor varying trial lengths, v~s~t frequencies, and outcome measures A one-year trial w~th quarterly ,.~s~ts demonstrated acceptable power tor an evaluation ot Leuclne w~th 100 patients Unreliability of Relapse Frequency as Predictor of Long Term Survival in Adjuvant Breast Cancer Rowan Chlebowskt, John Wemer, Victor Ryden, and Joseph Bateman, The Western Cancer Study Group, Los Angeles, Cahforma (P53) At present, clinical trials revolving adluvant therapy in breast cancer are commonly interpreted usmg early differences m relapsetrequencyasendpomt Begmmng m 1974, patients undergo- mg mastectomy at high risk tor recurrence (~4 nodes *) were randomized to receive either 5- FU or the drug combination CMF tor 12 months Median tollow up ot the 02 pahents now exceeds 66 months CMF s,gmticantly prevented early disease recurrence (3",, recurrence on CMF ~,~ 25% on FU at 12 months, p<001.) resulting m survival advantage during the initial 40 months Subsequently this difference was lost and relapse tree sur~lval (RFSI and overall survival at 5 5 years were RFS % Survival 5 -FU 36% 61% CMF 47~,, 47% The apparently paradoxical relationships between RFS and survival on FU was related to survival alter recurrence Pahents treated after recurrence hved slgmt~cantly longer on the FU compared to CMF arm (median <69 months vs 31 months, p<0 05) These results suggest that long term survival m adluvant breast cancer tmals may not be accurately predLcted by early differences m disease recurrence Protocol for Protocols Helen J Golenzer, Mayo Comprehenswe Cancer Center, Rochester, Minnesota (P54) In order to conduct a good chmcal trial, a well thought out, all-comprehensive protocol has to be developed and presented m an understandable, logical manner, covering all aspects necessary to achieve the desLred goals To make this task eas~er for the primary investigator, we have developed at the Mayo Chmc Oncology Department a structured, detailed outline for

Transcript of Use of a natural history phase for the design of trials for duchenne muscular dystrophy (DMD)

Page 1: Use of a natural history phase for the design of trials for duchenne muscular dystrophy (DMD)

8 2 A b s t r a c t s

easily and cheaply measured and with ~mportant and val,dated prognostic lntormatlon The use of randomized trials to prove the merits of such an attitude and to allow therapeutzc progress leads one to build prognostic classifications Within a prognostic class, one compares. with appropriate sample sizes, all or only a subset ot the treatments but adlacent prognostic classes receive at h_'ast one common treatment We have, set up two cooperative randomized studies of this kind (chronic lymphocytic leukemia, melanoma)

Use of a Natural History Phase for the Design of Trials for Duchenne Muscular Dystrophy (DMD) C o l l a b o r a t w e I n v e s t l g a t x o n ot D u c h e n n e D y s t r o p h y G r o u p , Washington Umvcrs;ty, St Louts, Mtssourt (P52) A collaborative s tudy ot DMD included a one-year natural h~story phase to chart the disease progress ion in boys of varying ages Since no single oblect~ve measurement provided an acceptable parameter tot the evaluation of therapeutic ethcacy, a variety ot laboratory meas- urements , functional g radmgs , and ratings of muscle strength and range ot motion data were collected for 100 patients on 8 visits spaced over a one-year interval lntra- and mterpatlent differences were evaluated in order to p rowde tmal design parameters An a~erage ot muscle strength evaluations at each time pemod proved to be particularly attrachve because ot ~ts reproducibf l l tyand hneanty wzth age The measurements over time allowed us t oe xa lua t e the ~atlhty of extended basehne periods m order to establish lndiwdual rates ot progression ot DMD This natural his tory phase also allowed tor the estimation of the expected changes in the parameters over time tacihtatmg sample s~ze calculations tor varying trial lengths, v~s~t frequencies, and outcome measures A one-year trial w~th quarterly ,.~s~ts demonstra ted acceptable power tor an evaluation ot Leuclne w~th 100 patients

Unreliability of Relapse Frequency as Predictor of Long Term Survival in Adjuvant Breast Cancer R o w a n C h l e b o w s k t , J o h n W e m e r , Vic tor R y d e n , a n d J o s e p h B a t e m a n , The Western Cancer Study Group, Los Angeles, Cahforma (P53) At present, clinical trials revolving adluvant therapy in breast cancer are commonly interpreted u smg early differences m r e l a p s e t r e q u e n c y a s e n d p o m t Begmmng m 1974, patients undergo- mg mastectomy at high risk tor recurrence (~4 nodes *) were randomized to receive either 5- FU or the drug combinat ion CMF tor 12 months Median tollow up ot the 02 pahents now exceeds 66 months CMF s,gmticantly prevented early disease recurrence (3",, recurrence on CMF ~,~ 25% on FU at 12 months , p<001.) resulting m survival advantage during the initial 40 months Subsequent ly this difference was lost and relapse tree sur~lval (RFSI and overall survival at 5 5 years were

RFS % Su rv iva l

5 -FU 36% 61% CMF 47~,, 47%

The apparently paradoxical relat ionships between RFS and survival on FU was related to survival alter recurrence Pahents treated after recurrence hved slgmt~cantly longer on the FU compared to CMF arm (median <69 mon ths vs 31 months , p < 0 05) These results suggest that long term survival m adluvant breast cancer tmals may not be accurately predLcted by early differences m disease recurrence

Protocol for Protocols H e l e n J G o l e n z e r , Mayo Comprehenswe Cancer Center, Rochester, Minnesota (P54) In order to conduct a good chmcal trial, a well thought out, al l-comprehensive protocol has to be developed and presented m an unders tandable , logical manner , covering all aspects necessary to achieve the desLred goals To make this task eas~er for the pr imary investigator, we have developed at the Mayo Chmc Oncology Department a structured, detailed outline for