Three pill bottles spilling.

The I-SPY 2 Breast Cancer Trial: How Clinical Trials May Be Changing

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It takes a very long time–thirteen years on average–for a new cancer drug to be developed, go through the standard clinical trials process and become available for patients.

Only a fraction of oncology drugs studied in clinical trials are successful. And the cost is extremely high at hundreds of millions of dollars to bring one new drug to patients. These facts, and the reasons behind this dysfunctional process, are discussed by Clifton Leaf in his book, “The Truth in Small Doses,” which I recently reviewed.

What can be done to bring better therapies to patients more quickly? One approach that is being tested is called “adaptive” clinical trial design.

There’s a trial going on right now in breast cancer that uses this type of design. It’s expected that, if successful, much wider use of the approach could follow. The first results from the trial, referred to as “I-SPY 2” were presented at the San Antonio Breast Cancer Symposium last December.

Adaptive clinical trials

In an adaptive clinical trial, the goal is to identify as rapidly as possible new drug therapies that show a likelihood of being successful in specific patient populations.

Patients’ responses to the drugs being tested are evaluated early on and throughout the trial. Possible changes or “adaptations” are defined before the trial starts and may be made as the trial goes along based on the accumulated data from the trial.

The types of adaptations that may be made include drug doses, the actual drugs being studied and patient selection criteria. This type of trial can be conducted with a relatively small number of patients compared to a traditional clinical trial.

There are risks with this type of approach, including the possibility of showing positive findings for drugs that aren’t really better than existing treatments. The FDA published a draft guidance document for the industry that addresses ways to design studies to minimize these risks.

The I-SPY 2 Trial

The I-SPY 2 trial, which started in 2010 and is expected to run for a total of five years, is intended to speed up the process of finding drugs that are effective for specific breast cancer subtypes.  Here are some of the key things to know about the trial and how it works:

  • To be eligible for the trial, patients must have a breast tumor measuring at least 2.5 cm and be considered to be at high risk for early recurrence.
  • The trial will evaluate a number of different investigational breast cancer drugs in at least 7 different study arms.
  • Drugs are given prior to surgery and their effectiveness is evaluated in the breast and lymph node tissue subsequently removed in surgery.
  • Patients are randomly assigned to receive the usual “standard of care” or a combination treatment that includes standard of care and also one of the investigational therapies, depending on their tumor characteristics including ER/PR status and HER2 receptor status.
  • New patients coming into the trial benefit from the experience of those already participating in that they are more likely to receive a treatment that has shown positive results so far.
  • Therapies “graduate” and move on to further study as they meet pre-set measures of the likelihood they will work.
  • Therapies are dropped and replaced by other candidate drugs if they are clearly not showing efficacy.

First results from I-SPY 2 and what happens next

At SABCS last December, researchers reported on the first novel therapy to graduate from the trial:

  • The therapy is actually a combination of two drugs–veliparib, a PARP inhibitor and carboplatin, a chemotherapy drug. Patients in the veliparib/carboplatin arm also received standard chemotherapy.
  • In this arm of the trial, 71 patients were randomized to receive the veliparib/carboplatin/standard chemo combination and a control group of 44 patients received standard chemo (all of these patients had HER2-negative breast cancer).
  • The veliparib/carboplatin combination showed good indications of effectiveness in patients with triple negative breast cancer–enough to meet a pre-set hurdle for moving on to further study.
  • As expected, toxicity was higher for the combination, but was able to be managed well by adjusting the amount and timing of doses.

The treatment will now move on to further testing with a somewhat larger group of patients (it’s suggested the number could be around 300) in a Phase III clinical trial. That trial will focus on patients with triple negative breast cancer, since the combo has shown indications of effectiveness in that particular subtype.

Meanwhile, the I-SPY 2 trial is ongoing, and is continuing to enroll patients. It’s expected that additional findings will be reported over the course of the remaining years of the trial.

More Information

The results from the I-SPY 2 trial were presented at the San Antonio Breast Cancer Symposium by Dr. Hope Rugo. Dr. Rugo’s presentation and slides are available on the SABCS website (choose SABCS on Demand, Browse by Presenters).

There is a very informative website for the I-SPY2 trial that includes patient-oriented background and information.

For additional background on adaptive clinical trials in general, a helpful article is Adaptive Clinical Trials: The Promise and the Caution by Donald A. Berry MD.

Related Posts
San Antonio Breast Cancer Symposium 2013: What Did We Learn?
Review of “The Truth in Small Doses” by Clifton Leaf

Photo credit: Andrew S via Shutterstock


  1. Thank you for a very informative post. My son had ALL from age 8 to 11 (and is a 13-year survivor), and I am three months into treatment for triple-negative breast cancer with no primary site identified. Clinical trials are fascinating, and this sounds like a blueprint for the future of trials and drug development. Thank you again for making it readable.

    1. I’m glad it was helpful. Good luck with the rest of your treatment – I hope it goes as smoothly as possible. Thank you for reading and commenting!

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