Opportunities and main challenges faced by clinical researchers

in LA – a young oncologist

investigator’s vision

Rachel Riechelmann MD - Assistant Oncologist GI Tumors

- Chief of Clinical ResearchInstituto do Cancer do Estado de Sao Paulo- Scientific DirectorBrazilian Gastrointestinal Tumors Group

LIMITATIONS TO LAUNCH AN ACADEMIC CAREER IN LA

Issues and Challenges

• Regulatory hurdles• Funding • Non-inferiority trials with cheaper drugs are nearly

impossible…1

• Accesss to new drugs– Developing countries are mostly “recruiting fields”– Investigator initiated trials are uncommon in the developing

world • Time protected for “creating” research• Hierarchical environment

Mailankody. NEJM 2014

So…

If you have limited time, little money, shortage of specialized personnel, few people to count on….

….but

you love research

What do you do?

BE CREATIVE!!!!

Opportunities in LA

1. Pragmatic questions1. Trials of cancers common in LA2. Trials of rare cancers

2. Testing old (cheap) drugs3. Patient-reported outcomes3. When the sujbect is the study:

3. Meta-analyses4. Critical appraisal

Saad ED, Katz A, Riechelmann R. Rev SBOC 2011

Pragmatic question: how much are cancer patients at risk of dangerous drug-drug

interactions?

Pragmatic Trials at ICESP

– Phase III adjuvant FLOX vs observation in stage III rectal cancer (NCT01941979)

– Phase II surgery vs watch and wait in rectal cancer after complete response with chemorads (NCT02052921)

– Phase II trial of dose-reduced first line chemo in ECOG 3/4 (not yet registered)

– Phase III trial of adjuvant chemoradiation with 5FU/LV vs observation in billiary cancer (not yet registered)

Examples of pending pragmatic questions…

• Second line treatment for– Biliary cancer– Head and neck– Esophageal cancer

• First line treatment for metastatic anal cancer• Dose escalation of SSA in NETs

Dowling et al. J Mol Endocrinol. 2012;48:R31-R43.

Metformin: A New-Old Antitumor Agent

Trials of old drugs: metformin

– Phase II of metformin and 5FU in refractory mCRC (NCT01941953)

– Phase II metformin + paclitaxel in gemcitabine-refractory pancreatic cancer (NCT01971034)

– Phase II trial of metformin in NET (not yet registered)

Old drugs with potential clinical affect against cancer

• Aspirin

• Statins

• Omeprazole

Patient-reported outcomes

• Complex but relatively cheap to perform

• Ex. of poorly explored issues:

– Sexual function

– Terminally ill• Ex futile meds (Supp Care in Cancer)

– Spirituality

Chemoholiday or treatment given until progression in mCCR?

Pereira A, Rego J, Sasse A, Riechelmann R. ASCO 2014Under review JNCI

• Reasons for designing NIF (N=62): • 23 (30%): convenience• 15 (15%): less toxicity • 9 (12%): either above• 11 (15%): less dose-intensity• 2: cheaper • 13 (17%) me too drugs,

… most with drug approval

• Median noninferiority margin for time-to-event primary endpoints:

• HR: 1.25 (1.10-1.50)

Other examples of critical appraisal of the literature

Conclusions

• Many limitations to develop clinical research in LA– Time protected– Funding – Mindset

“difficulty is gasoline on the fire of human creativity”

Flowers from greenhouses

Cerrado - Brazil