Clinical trials: What are they? What are phase I and phase II trials?
Therapeutic
clinical trials treat patients. You may hear about phase I clinical
trials—these are the first clinical trials that test a therapy in
humans. These take place after a new drug is tested in the laboratory,
in animals, and it’s been found to be safe. Typically, the drug also
shows anti-cancer activity in the laboratory. The side effects are
studied in dogs or rats or monkeys, and in the phase I trials, the drug
is going to be tested in humans for the first time. The main purpose of
the study is to look for side effects in people.
The second
purpose of phase I trials is to pick the right dose of the drug for
future testing. You start with a very small dose, make sure that there
are no serious side effects, and then you increase the dose. You keep
increasing the amount of the drug until you find the dose that gives
side effects that are unacceptable. Older drugs usually wiped out your
white cells at higher doses, and at that point we’d say the dose was
too high. So we’d go to the next lower dose. For example, if we give 10
mg and people are fine, and then we give 15 mg and everybody gets their
white counts wiped out, we’d say that the 15 mg dose was too high and
that 10 mg is the right dose.
Once we find the right dose—and
while we are looking for it—we pay attention to any inkling of clinical
activity of the drug. Then, for example, if someone with breast cancer
has tumor shrinkage on a phase I trial, this may lead us to test that
drug further in breast cancer patients in phase II trials.
However,
in phase I trials we generally treat people with all types of cancer.
The usual requirement for a cancer patient to participate in a phase I
trial is that all the standard treatment options have been exhausted.
Phase I trials tend to be full of the common cancers, so usually most
of the folks in phase I trials have lung, colon, breast and prostate
cancer. For example, we don’t see a lot of brain tumors and liver
cancers on these studies just because they are not as common.
Phase
II studies are aimed at finding out if the drug works. Here all the
patients have a particular tumor type. So if in phase I, there is
evidence that a drug might be helpful for lung cancer, then in phase
II, the drug is tested in lung cancer patients. If it looks like it
might be helpful for breast cancer, then in phase II, it is tested in
breast cancer patients. Also, in phase II trials, there’s just one dose
of the drug, unlike phase I, which has multiple doses. Everybody has
the same tumor in phase II and investigators look for evidence that the
drug works for that type of cancer.
Now, let’s say that for lung
cancer, our best treatment until now will shrink tumors in about three
out of 10 people. If I do a phase II trial with a new drug and it
shrinks the tumor in five out of 10 study participants, then this means
the drug is promising and might be better than our best treatment. Such
a drug might be further tested in phase III trials. In a phase III
trial, we’re going to compare this new drug directly to the best
standard treatment. And, if this new drug is better than our best
treatment, then it becomes the new standard. So this is how we get new
drug treatments for cancer. Sometimes, the new treatment may not be
better than the old one, but it might have fewer side effects, and in
that case, too, it can get approved.
So to summarize: Phase I
studies enroll patients with all kinds of cancers. Typically, there’s
no other effective treatment available to these patients. Phase II
studies are for a defined patient population. For instance, in breast
cancer, the treatments for women who are newly diagnosed are very good.
So, a lot of times you are not going to test a new drug in newly
diagnosed women for a phase II trial. Instead, you might test the new
drug in what we call third-line therapy—in women who have taken two
different chemotherapy regimens, such as Herceptin and Taxol and then
Adriamycin. In a phase II study the participants all have to be in the
same group—so, in the last example, everybody in the study should be a
breast cancer patient who already tried two different chemotherapy
treatments. Or, for example, if the drug is intended for pancreatic
cancer, where the front-line treatment is not very good, then phase II
could test the drug on newly diagnosed pancreatic cancer patients.
Sometimes
a drug shows promise during phase I for many different types of tumors,
and then there are different phase II studies for each type of tumor.
There’s a new drug that was approved last year for lung cancer and
mesothelioma called Alimta. We had studied it in phase I and saw
activity in a broad range of tumors. So phase II studies were started
for a lot of cancers, including breast, lung, mesothelioma, pancreas
and colon. There are other times where activity is seen in only one
tumor type, so then the drug is tested in only that one cancer.
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