Targeted Therapy Clinical Trial
A targeted therapy clinical trial tests a drug matched to a gene change in the tumor. Matching lifts response rates in early trials from 4.9 to 30.6 percent, yet only 17.8 percent of patients screened in the largest national trial found a matching arm. We explain how these trials work, their risks, your rights, and how we help you search.
About This Department
A targeted drug matched to a gene change works far better than one given blind. Trials are where that matching is tested safely.
A targeted therapy clinical trial tests a drug aimed at a specific change in the tumor, a gene mutation or fusion found by sequencing in most cases. For patients whose cancer has outgrown standard treatment, such a trial can offer a drug not yet available otherwise. The evidence explains why the match matters. Across 346 early trials, arms that selected patients by a biomarker had a median response rate of 30.6 percent, against 4.9 percent in arms that did not. Yet in the largest national screening trial only 17.8 percent of patients found a treatment arm, so most who look will not find a trial that fits.
Patients search for a targeted therapy clinical trial once standard options run short, or when a gene report names a change and nobody at home can say what to do with it. This page explains how these trials work, what the evidence says about matching drugs to genes, what an early trial offers and risks, what rights participants keep, and how our oncologists help a patient abroad find out whether a trial is a realistic option.
How targeted therapy trials are built
Organized around the gene
Basket trials
One gene change, many cancers
Umbrella and platform trials
One screening, many arms
The phases
Phase 1, 2 and 3
What each phase asks
- Phase 1 finds a safe dose and the main side effects, in small groups, and in targeted therapy it increasingly enrolls only patients whose tumors carry the target
- Phase 2 asks whether the drug shrinks tumors in a defined group, and many targeted drugs have been approved on phase 2 results when the change is rare and the responses large
- Phase 3 compares the new drug against the current standard in hundreds or thousands of patients, usually by random allocation
- In every phase, participants receive at least the care they would have received anyway, and nobody with a known effective treatment is given a placebo in its place
Why the gene test comes first
What the largest screening trial found
What a test finds
An actionable change
A mutation, fusion or amplification for which an approved drug or a trial exists.
Ask first whether an approved drug already fits. An approved drug needs no trial, carries known risks, and can be given at home, so a trial comes second whenever an approved match exists, even when the trial looks exciting.
A change with no drug, or none at all
The majority fall here. The report still helps. It rules out treatments that will not work, it points to trials that may open later, and it belongs in the file.
What the evidence says
Matching lifted response sixfold in early trialsA meta-analysis of 346 phase 1 trials published between 2011 and 2013 found a median response rate of 30.6 percent in arms that selected patients by a biomarker, against 4.9 percent in arms that did not, and median progression-free survival of 5.7 against 2.95 months. Treatment-related deaths did not differ, 1.89 against 2.27 percent. Targeted drugs given without a biomarker did no better than chemotherapy. Schwaederle and colleagues, JAMA Oncology, 2016.
Two lessons from randomized and matched studies
Matching works inside a trial
In one NCI-MATCH arm, 29 patients with BRAF V600E mutations in cancers other than melanoma, thyroid and bowel received dabrafenib with trametinib. Thirty-eight percent responded. Responses came in seven tumor types, and seven lasted over a year. Salama and colleagues, Journal of Clinical Oncology, 2020.
Off-label matching outside a trial did not
In France, the SHIVA trial tested a different approach and randomized 195 heavily treated patients to a targeted drug chosen from their tumor profile but used outside its approval, or to the doctor's standard choice. Median progression-free survival was 2.3 against 2.0 months. No real difference. The authors advised against off-label use and in favor of trials. Le Tourneau and colleagues, Lancet Oncology, 2015.
Finding and joining a trial
Two stages
Finding
Joining
Benefit and risk in early trials
What the numbers show
The chance of benefit
Phase 1 response rates
The risk of harm
Toxicity in phase 1
Your rights as a participant
Consent and withdrawal
Informed consent
Every consent document explains the purpose, the drug, the visits, the known risks, what happens to samples and data, and who pays for what. Take it home. Read it with family, ask every question, and sign only when you understand it, with a translated version or an interpreter where needed.
Leaving a trial
You can leave at any point. The trial team then helps arrange the next treatment. Data already collected are kept unless you ask otherwise, as the consent form states, because removing them after the fact can distort the results for every other patient in the study and for those who will be treated with the drug in years to come.
Who can take part
How we help, and the trip
Length of stay, cost and the trip
Questions to ask, and follow-up
Take these questions to any trial team.
This table scrolls sideways on a narrow screen. Swipe or drag to see every column.
| Question | Why it matters |
|---|---|
| What phase is the trial, and what is it testing? | Early phases focus on safety and dose, later ones on benefit |
| Which gene change does it target, and how was the drug chosen for it? | The match is the reason to join |
| What happened to earlier patients? | Early response and side-effect data guide the decision |
| How often must I come, and for how long? | Frequent visits rule many patients from abroad out |
| What costs does the sponsor cover? | Drug, tests, travel and accommodation vary between trials |
| What happens if I leave or the drug stops working? | Your next treatment should be planned from the start |
Once you are back home, the file and our written advice go to your own oncologist, whether you join a trial or not. Questions on a trial that opens later, a new gene report, or a change in your condition can come straight back to us, and the coordinator stays reachable on the same WhatsApp number to pass them to the oncologist who reviewed your case. Many patients check in again every few months, since trials open and close all the time and a match that did not exist in spring can appear by autumn. Keeping the gene report current helps with that. If the cancer changes under treatment, a new biopsy or a blood test for tumor DNA can reveal a new target, and the search starts again with the new result in hand, from the same file and with the same team, so nothing is lost between one review and the next. A single, complete file that follows you makes that possible.
Targeted Therapy Clinical Trial FAQ
What is a targeted therapy clinical trial?
How do I know if I qualify for a targeted therapy trial?
Do targeted therapy trials work?
Is it safe to take part in an early phase trial?
Can I take a targeted drug off-label instead of joining a trial?
Can a patient from abroad join a trial?
References
- Flaherty KT, Gray RJ, Chen AP, et al. Molecular Landscape and Actionable Alterations in a Genomically Guided Cancer Clinical Trial, National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH). J Clin Oncol. 2020;38(33):3883-3894.
- Salama AKS, Li S, Macrae ER, et al. Dabrafenib and Trametinib in Patients With Tumors With BRAF V600E Mutations, Results of the NCI-MATCH Trial Subprotocol H. J Clin Oncol. 2020;38(33):3895-3904.
- Schwaederle M, Zhao M, Lee JJ, et al. Association of Biomarker-Based Treatment Strategies With Response Rates and Progression-Free Survival in Refractory Malignant Neoplasms, A Meta-analysis. JAMA Oncol. 2016;2(11):1452-1459.
- Le Tourneau C, Delord JP, Goncalves A, et al. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA), a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol. 2015;16(13):1324-34.
- Horstmann E, McCabe MS, Grochow L, et al. Risks and benefits of phase 1 oncology trials, 1991 through 2002. N Engl J Med. 2005;352(9):895-904.
Editor's note
Written by the Biruni Hospital medical editorial team. Reviewed by Prof. Dr. Özcan YILDIZ, Medical Oncology.
Medically reviewed by
Prof. Dr. Özcan YILDIZ
Medical Oncology
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