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
Medical Oncology
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.
30.6% vs 4.9%
Response with and without biomarker selection, JAMA Oncol 2016
17.8 in 100
Patients screened who were assigned to a trial arm, J Clin Oncol 2020
0.49 in 100
Deaths from toxicity in 11,935 phase 1 participants, NEJM 2005
Free
Oncologist review of your gene report and history
Free consultation
Send the pathology report, any gene sequencing report, the latest scans and a list of every treatment so far with dates and the reason each one stopped. A medical oncologist reviews them, says whether a gene test is still needed, and tells you whether a trial, an approved targeted drug or standard treatment is the better next step. The review is free and binds you to nothing.
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
A basket trial gives one drug to patients with the same gene change, whatever organ the cancer started in. A BRAF mutation in a bile duct cancer, an ovarian cancer and a brain tumor can all enter the same basket. The design exists because rare changes turn up across many cancers, and no single cancer type would supply enough patients.
Umbrella and platform trials
One screening, many arms
An umbrella or platform trial sequences each patient's tumor once and then sends the patient to whichever of many arms matches the result. New arms open as drugs arrive and old ones close as questions are answered. The American NCI-MATCH trial, the largest of its kind, ran about 30 arms in parallel from more than 1,100 hospitals.
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
NCI-MATCH sequenced tumor biopsies from 5,954 patients whose cancers had progressed on standard treatment. Sequencing worked in 93.0 percent. An actionable change, one that a drug in the trial could target, was found in 37.6 percent. After the eligibility rules were applied, 17.8 percent were assigned to a treatment arm. The rate varied by cancer, over 35 percent in bladder cancer and under 6 percent in pancreatic and small cell lung cancer. Flaherty and colleagues, Journal of Clinical Oncology, 2020.
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 trials
A 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
1
Know the change
The exact gene, the exact variant and, for fusions, the partner gene. Trials are listed by these.
2
Search the registries
Public registries such as ClinicalTrials.gov and the EU Clinical Trials Register list open trials by gene, cancer and country. Our oncologists run this search with you.
3
Check the fine print
Each trial lists inclusion and exclusion rules, such as prior treatments, brain metastases, organ function and fitness, and many patients who match the gene fail one of these. Read them before hoping.
Joining
1
Contact the trial site
The trial team decides eligibility. Our oncologist can send the referral and the file.
2
Screening
Consent, new scans, blood tests and often a fresh biopsy, over two to four weeks.
3
Treatment and visits
Visits are frequent, especially in the first two months, and most trials require treatment and follow-up at the trial site.
Benefit and risk in early trials
What the numbers show
The chance of benefit
Phase 1 response rates
A review of 460 phase 1 trials with 11,935 participants, run between 1991 and 2002, found an overall response rate of 10.6 percent, with another 34.1 percent having stable disease. Response was 4.4 percent in classic single-drug chemotherapy trials and 17.8 percent in trials that included an approved anticancer drug. Horstmann and colleagues, New England Journal of Medicine, 2005. Biomarker-selected targeted trials since then have done considerably better, as the meta-analysis above shows.
The risk of harm
Toxicity in phase 1
In the same review, 0.49 percent of participants died of treatment toxicity, and 14.3 percent of those with detailed data had at least one grade 4, life-threatening, toxic event. The risk depends heavily on the drug and the dose level, so each trial's consent document should state what is known.
Your rights as a participant
A trial is research. Participants volunteer, and they keep the right to stop at any time, for any reason, without losing their normal care. An independent ethics committee must approve every trial before it starts, and a data monitoring committee watches for harm while it runs.
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
1
The right change
A tumor carrying the gene change the trial targets, confirmed by a test the trial accepts.
2
The right point in the illness
Most early targeted trials enroll patients whose cancer has progressed on standard treatment, or who have no standard option.
3
Enough strength
Patients up and about for most of the day, with adequate blood counts, liver and kidney function.
4
The ability to attend
Frequent visits to the trial site, usually for months, which is the practical barrier for many patients from abroad.
How we help, and the trip
1
Review
Our medical oncologists review the history, the pathology and any gene report, and check first whether an approved drug already fits.
2
Testing
If no broad gene test has been done, we advise which test, on which tissue, and can arrange it.
3
Search
We search registries with you for open trials matching the change, the cancer and the countries you can reach, and explain the eligibility rules of each.
4
Referral
Where a trial fits, we send the referral and file to the trial team and explain in writing what joining would involve.
Length of stay, cost and the trip
A review needs no travel. A visit to Istanbul for testing and consultation takes three to five days, after which you can fly home or to a trial site. Trial drugs are normally provided by the trial sponsor, while travel, accommodation and some tests may not be, and each trial states this in its consent form. Our review of your reports is free, and any test is quoted before it is done. The coordinator writes in English, Arabic, French, Russian, Serbian, Romanian or Spanish, or arranges an interpreter, sends the appointment confirmation and an invitation letter naming the hospital and the treating doctor ten days before a visit, and books the hotel and transfers. Two family members may join consultations, meals come in halal, vegetarian and diabetic versions, a prayer room is on site, and a female doctor can be requested at first contact.
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.
Questions worth asking before joining a trial
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?
A study testing a drug aimed at a specific change in the tumor, usually found by gene sequencing. Basket trials group patients by the gene change across cancers, and umbrella or platform trials sequence patients once and assign them to matching arms.
How do I know if I qualify for a targeted therapy trial?
The tumor must carry the change the trial targets, the cancer must be at the right point in its course, organ function and fitness must meet the trial's rules, and you must be able to attend the trial site. The trial team makes the final decision.
Do targeted therapy trials work?
Matching helps. In early trials, biomarker-selected arms had a median response rate of 30.6 percent against 4.9 percent without selection. But only 17.8 percent of patients screened in the largest national trial were assigned to an arm.
Is it safe to take part in an early phase trial?
There are risks. In a review of 11,935 phase 1 participants, 0.49 percent died of toxicity and 14.3 percent of those with detailed data had a life-threatening toxic event. Each trial's consent document sets out what is known.
Can I take a targeted drug off-label instead of joining a trial?
The evidence advises against it. In the randomized SHIVA trial, targeted drugs chosen from tumor profiling and used off-label did not improve progression-free survival compared with standard choice.
Can a patient from abroad join a trial?
Sometimes. Many trials accept international patients, but most require frequent visits to the trial site for months. Our oncologists review your case, search for matching trials and help with referral where one fits.
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.
