DELPHI
Overview
- Patients with tumours in the back of the throat (oropharynx) can participate in the DELPHI study.
- Their cancer must be squamous cell carcinoma that has already been operated on. In addition, radiotherapy with or without simultaneous chemotherapy must be planned as the next treatment step.
- DELPHI is investigating how a lower radiation dose after surgery affects the risk of recurrence and long-term side effects.
Study status: The programme is currently accepting patients (recruitment open).
Not all cancer cells are the same. They differ in their biological and genetic characteristics. These differences also influence how well a particular therapy works. This is why one type of treatment may work very well for one person, and not so well, or less well, for another.
Researchers observe such differences very closely. Sometimes this allows them to draw conclusions about a connection between a tumour characteristic and the effect of treatment. Such research results enable those affected to receive a more targeted treatment.
That is why researchers in the DELPHI study are investigating whether a lower dose of radiation after surgery is sufficient for patients with such tumours. They hope that this will result in fewer side effects with treatment success rates remaining unchanged.
- You can read more about the specific goals of the scientists involved in DELPHI in the section What is the goal of the DELPHI study?.
Which types of cancer are covered by DELPHI?
Patients with squamous cell carcinoma in the back of the throat can participate in the DELPHI study. However, they must meet various requirements. The most important ones are:
- The tumour has already been surgically removed.
- The surgery is to be followed by radiotherapy or radiotherapy combined with chemotherapy (chemoradiotherapy).
- Participants do not have distant metastases.
For information on the other requirements that patients must meet in order to participate in the study, please refer to the section Who is the study suitable for?.
What is the aim of the DELPHI study?
DELPHI is an abbreviation for the study title "De-escalation of adjuvant radio(chemo)therapy for HPV-positive head and neck squamous cell carcinomas. A phase I study to reduce late toxicity". Translated, this means:
In a phase I study, researchers are investigating
- in patients with HPV-related squamous cell carcinoma of the back of the throat (oropharynx)
- whether the radiation dose can be reduced in post operative radiotherapy or chemoradiotherapy
- to reduce late effects without worsening the chances of recovery.
Objectives of the DELPHI study
The scientists involved in the DELPHI study aim to
- to show that a lower radiation dose is also safe for the above-mentioned group of patients after surgery.
- to determine the frequency of relapses after radiotherapy with a lower radiation dose.
- record acute and long-term side effects of radiotherapy with a lower radiation dose.
- to find a lower, but safe, radiation dose with the goal of continuing the study with a larger group of patients.
Patients can participate in the study if all the following requirements are met:
- The participant is 18 years of age or older.
- The participant has had squamous cell carcinoma in the back of the throat and associated lymph nodes removed.
- The tumour board recommends radiotherapy or chemoradiotherapy after surgery.
- The patient's health is not impaired or is only slightly impaired: experts classify the performance status according to the Eastern Cooperative Oncology Group (ECOG) as 0 or 1.
- The patient is willing to sign a written consent form.
- The patient is willing to attend the necessary appointments and examinations as part of the study observation. He or she agrees to complete questionnaires about his or her own well-being.
Patients cannot participate in the study if at least one of the following points applies:
- The cancer has metastasised or there are indications of metastasis.
- There is visible residual tumour after surgery.
- More than 7 weeks have passed between the last operation and the planned start of radiotherapy.
- Previous radiation makes it too risky to repeat radiation in the same area.
- There are medical reasons preventing the use of the recommended radiotherapy or chemoradiotherapy.
- The participant has previously had a tumour in the head and neck area.
- Another tumour disease was present in the 5 years prior to the start of the study (except for: basal cell carcinoma of the skin, in situ tumours of the cervix or breast, or similar tumours that are considered very likely to be cured).
- The cervical lymph nodes were not removed during surgery.
- For women: The patient is pregnant or breastfeeding.
- The patient is already participating in another cancer treatment study. Only participation in observational studies or studies on supportive treatment (supportive therapy) is permitted.
- The person concerned is unable to assess the nature and scope of the clinical trial and its possible consequences due to illness or other accompanying circumstances.
- There are indications that the patient is not cooperating sufficiently with the treatment team.
- Written consent is missing.
The DELPHI study is a:
- multicentre study: patients can participate in various study centres in Germany.
- two-arm study: The study compares two groups of participants with each other.
- non-randomised study: patients are not assigned to the control or treatment group at random, but rather in a targeted manner and according to specific characteristics over the course of the study.
- Therapy study: Doctors investigate a modified version of a proven treatment.
- Phase I study: The treatment is being tested on humans for the first time.
During this consultation, the study doctor will provide participants with detailed information about the study. If they wish to participate, they must submit a written declaration of consent. They can also indicate whether they would like to be informed about any additional hereditary disease risks that may be found.
(2) Laboratory tests, HPV test
For the examination, the researchers need blood samples and a sample of the tumour that has already been surgically removed. This sample is examined in the laboratory to determine whether the tumour was caused by infection with the human papillomavirus (HPV). It takes about 1–2 weeks for participants to receive the results of the examination. Blood and tissue samples will be stored and used for further research.
(3) Initial study phase and interim analysis
In the first phase of the study, participants were assigned to either the treatment or control group depending on the results of the HPV test. Participants with HPV-positive tumours in the treatment group usually received conventional radiotherapy with a lower radiation dose (intensity-modulated radiotherapy, IMRT).
Patients with HPV-negative tumours in the control group received radiation at the usual dose.
Participants with a high risk of recurrence in both groups received chemotherapy in addition to radiotherapy.
An interim evaluation has shown that the reduced radiation dose has not led to more relapses in the treatment group so far. The study will therefore now continue as follows:
(4) Second study phase – inclusion of additional participants
In the second phase of the study, the researchers can now assign additional participants to the study groups:
- Treatment group: This group includes 60 participants whose tumours were caused by HPV infection. They receive radiotherapy with a dose that is even lower than that received by participants in the first phase of the study.
- Control group: This group includes all participants whose tumours were not caused by HPV infection. They receive radiation therapy at the usual dose.
In all groups, participants with a high risk of recurrence will also receive chemotherapy.
Patients receiving proton radiotherapy (intensity-modulated proton therapy, IMPT) can participate in the study and will also be included in the groups. Proton therapy is not available at all study centres. An interim analysis of the data collected after 24 months showed that fewer than 2 relapses occurred in the first 10 participants in the treatment group. This means that the study can now be continued with an even lower radiation dose.
(5) Final analysis of the data
Once all participants have completed a 24-month follow-up period, the researchers will evaluate the data. Depending on the results, they will then be able to determine a safe radiation dose for a further study.
(6) After the end of the study
After the end of the study, participants are entitled to the same follow-up examinations as those who did not participate in the study.
These are the potential benefits of participating in the DELPHI study:
- Very well-controlled therapy and follow-up care.
- If accepted into the treatment group, there is a chance of fewer side effects and fewer long-term and late effects of radiotherapy.
However, there may also be disadvantages to participating in the DELPHI study:
- Based on the current state of scientific knowledge, researchers also consider radiation with a lower dose to be safe. Nevertheless, the risk of relapse could be slightly increased if you are assigned to the group receiving the lower radiation dose.
- Side effects, long-term and late effects of radiotherapy can occur in all groups. Based on current knowledge, the benefits of radiotherapy outweigh these risks.
- Blood sampling as part of the study carries minor risks such as bleeding, nerve damage due to a missed puncture or inflammation.
- Further laboratory tests may reveal genetic changes that indicate a higher risk of certain diseases. Participants will then be informed (if they have consented to the disclosure of this information) of future health risks, which may also apply to family members. However, it is possible to participate in the study but decline the additional genetic testing.
- Despite comprehensive data protection and high data security, there is a small residual risk that genetic data could be traced back to the individual if this data falls into the wrong hands.
Where is the study being conducted?
Cancer patients can participate in the DELPHI study at many of the Comprehensive Cancer Centres or clinics of the NCT or the German Consortium for Translational Oncology (DKTK).
The sites Dresden, Heidelberg, Tübingen, Essen, LMU Munich, TU Munich, Frankfurt, Freiburg, Ulm, Regensburg and Berlin are currently recruiting participants. Further recruitment locations are in preparation. Those interested can find out which locations are currently accepting participants by contacting the study centre in Dresden.
What costs will participants incur?
Participation in the study is free of charge for patients. However, they will not receive any expense allowance. Travel costs will not be reimbursed as part of the study.
If you have any questions about the financing of the study, please ask the study team, for example, during the informed consent process.
The costs of any proton radiation therapy are not covered by the study. It is possible that participants in the study may receive proton radiation therapy. In this case, the study centre will provide them with information on how to have the costs covered by their health insurance. If the health insurance company does not agree to cover the costs, participants have two options:
- Cover the costs of proton radiation therapy themselves.
- Undergo treatment with conventional radiotherapy.
Both options are possible within or outside the study.
How many participants will the study accept? Where are there still places available?
A total of 304 patients are expected to participate in the DELPHI study.
Recruitment is currently open. This means that the study is still accepting participants – probably until the 30th of November 2027. Those interested can find out how many places are still available from the participating study centres.
In principle, any oncologist can register patients for DELPHI. Interested cancer patients should first talk to their treating physician. This will clarify whether the study is suitable for them in principle. If this is the case, the physician can contact the nearest study centre.
The documentation and information required for registration are available from the NCT Dresden study clinic at str.studien-at-uniklinikum-dresden.de. The treating oncologist fills out the documents and registers the patients.
Is participation possible? If so, a consultation will follow at one of the study centres.
Scientific publications (selection)
Mesia R, Taberna M. HPV-related oropharyngeal carcinoma de-escalation protocols. The Lancet Oncology. 2017 Jun. 18(6):704-705. doi:10.1016/S1470-2045(17)30250-4
Chen A, Felix C, Wang PI, et al. Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: a single-arm, phase 2 study. The Lancet Oncology. 2017 Apr, 18(6): 803-811. doi: 10.1016/S1470-2045(17)30246-2
Chin RI, Spencer CR, DeWees T, et al. Reevaluation of postoperative radiation dose in the management of human papillomavirus–positive oropharyngeal cancer. Head Neck. 2016 Nov, 38(11):1643-169. doi:10.1002/hed.24486
This study description was prepared by authors from the Cancer Information Service, under the direction of Dr. S. Weg-Remers, based on the study documentation.