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Anal CancerPhase 2RADIANCENCT04230759

Radiochemotherapy +/- Durvalumab for Locally-advanced Anal Carcinoma. A Multicenter, Randomized, Phase II Trial of the German Anal Cancer Study Group

A Phase 2 study testing Chemotherapy, Radiation and Durvalumab in people with Anal Cancer and Anal Carcinoma, run by Goethe University at 25 sites in 3 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The RADIANCE multicenter, randomized phase II trial will assess the efficacy of durvalumab, a PD-L1 immune checkpoint inhibitor, in combination with primary mitomycin C (MMC)/5-fluorouracil (5-FU)-based radiochemotherapy (RCT) in patients with locally-advanced anal squamous cell carcinoma (ASCC). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Anal Cancer, Anal Carcinoma, Anal Cancer Stage III
What is being tested?
Chemotherapy, Radiation and Durvalumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
180 participants
Where
25 sitesin 3 countries
Study dates
7 Jan 2020to 31 Mar 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically-confirmed ASCC (both genders) of the anal canal or the anal margin
  • UICC-Stage IIB-IIIC including T2>4cm Nany (IIB: T3N0M0; IIIA: T1-2N1M0; IIIB: T4N0M0; IIIC: T3-4N1M0; T2>4cm Nany) according to proctoscopy, pelvic MRI, CT scan of thorax and abdomen, all within 30 days prior to recruitment
  • Age ≥ 18 years, no upper age limit
  • ECOG-Performance score 0-1
  • History/physical examination within 30 days prior to recruitment
  • Written informed consent and any locally-required authorization (e.g. EU Data Privacy Directive in the EU) obtained from the patient prior to performing any protocol-related procedures, including screening evaluations
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  • Life expectancy of > 12 months
  • Body weight >30kg
  • Hemoglobin ≥9.0 g/dl
  • Leukocytes >3.5 x 10 ^9/l
  • Absolute neutrophil count (ANC) 1.5 x 10 9/l (> 1500 per mm3)
  • Platelet count ≥100 x 109/l (>100,000 per mm3)
  • Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). (This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
  • AST (SGOT), ALT (SGPT), AP ≤ 3x institutional ULN
  • Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula creatinine clearance
  • Female subject of childbearing potential should have a negative serum pregnancy within 72 hours prior to receiving the first dose of durvalumab. A highly sensitive pregnancy test must be used.
  • Female subjects of childbearing potential must be willing to use a highly effective contraceptive measure as defined in the Clinical Trial Facilitation Group (CTFG) guideline ("Recommendations related to contraception and pregnancy testing in clinical trials"). Highly effective contraception is required from screening to 90 days after the last dose of durvalumab. (Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.)
  • Male subjects of childbearing potential must agree to use a highly effective method of contraception, starting from screening to 90 days after the last dose of durvalumab. (Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.) Male patients should refrain from fathering a child or donating sperm during the study and for 180 days after the last dose of durvalumab + any drug combination therapy or 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period.
  • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • For HIV-positive patients: running combined antiretroviral therapy (CART) on a stable dose at study entry and undetectable HIV-viral load (HIV Viral load <50 copies/mL and CD4>200/mircoliter). Patients will be closely monitored and CART management will be performed according to appropriate labelling guidance of the antiviral therapy. CART should be on a stable dose at study entry.

Who cannot join

  • UICC-Stage I-IIA ASCC defined as cT1N0M0 or cT2 <4cm N0M0 disease
  • Second malignancy other than basalioma or cervical/genital/ neoplasia in situ
  • History of another primary malignancy except for:
  • Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of durvalumab and of low potential risk for recurrence
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated carcinoma in situ without evidence of disease
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  • Known DPD-deficiency
  • Participation in another clinical study with an investigational product during the last 12 months
  • Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
  • Any previous treatment with other immunotherapy, a PD1 or PD-L1 inhibitor
  • QT interval corrected for heart rate (QTc) ≥470 ms
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/d of prednisone, or an equivalent corticosteroid. In case of recent introduction of CART, inclusion will be possible provided subjects had at least 4 weeks of treatment prior to inclusion.
  • Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria:
  • Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Chairman.
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Chairman
  • Any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment, other than the study medication. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
  • Previous radiotherapy treatment to the pelvis or radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug
  • Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of durvalumab.
  • History of allogenic organ transplantation.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that does not require systemic therapy
  • Patients without active disease in the last 5 years may be included but only after consultation with the study chairman
  • Patients with celiac disease controlled by diet alone
  • Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
  • History of leptomeningeal carcinomatosis or any other metastatic disease
  • History of active primary immunodeficiency
  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of durvalumab. Note: Patients, if enrolled, should not receive live vaccine whilst receiving durvalumab and up to 30 days after the last dose of durvalumab.
  • Known allergy or hypersensitivity to any of the study/investigational drugs or any of the study/investigational drug excipients and/or radiochemotherapy with 5-FU and Mitomycin C.
  • Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab.

Trial locations and contacts

25 sites in 3 countries.

25 sites in 3 countries

Germany23 sites

  • Radioonkologie und Strahlentherapie

    Berlin, State of Berlin, 12203

  • OnkoLibri GbR

    Berlin, 14195

  • Institut für Radioonkologie und Strahlentherapie

    Darmstadt, Darmstadt, 64283

  • Klinik und Poliklinik für Strahlentherapie und Radioonkologie

    Dresden, Dresden, 01307

  • Klinik und Poliklinik für Strahlentherapie

    Essen, Hesse, 45122

  • University Hospital Goethe University Frankfurt

    Frankfurt, 60590

  • Klinik für Strahlenheilkunde, Universitätsklinikum Freiburg

    Freiburg im Breisgau, Freiburg, 79106

  • Universitätsmedizin Göttingen

    Goettigen, 37075

  • Asklepios Klinik Altona

    Hamburg, 22763

  • UKSH Campus Kiel

    Kiel, Kiel, 24105

  • Universitätsklinikum Leipzig

    Leipzig, Leipzig, 04103

  • Universitätsklinikum Magdeburg

    Magdeburg, Magdeburg, 39120

  • Universitätsmedizin Mainz

    Mainz, Mainz, 55131

  • Uniklinikum Marburg

    Marburg, Marburg, 35043

  • Kliniken Maria Hilf GmbH Mönchengladbach

    Mönchengladbach, Mönchengladbach, 41063

  • LMU Klinikum der Universität München

    München, München, 81377

  • Technische Universität München

    München, München, 81675

  • Universitätsklinikum Regensburg

    Regensburg, Regensburg, 93053

  • Hospital Barmherzige Brüder

    Regensburg, 93049

  • Universitätsklinikum Rostock

    Rostock, Rostock, 18059

  • Klinikum Stuttgart

    Stuttgart, 70174

  • Universitätsklinik Tübingen

    Tübingen, Tübingen, 72076

  • Universitätsklinikum Würzburg

    Würzburg, Würzburg, 97080

Other trials in Germany

Austria1 site

  • Univeritätsklinik für Strahlentherapie-Radioonkologie

    Graz, 8036

Other trials in Austria

Switzerland1 site

  • UniversitätsSpital Zürich

    Zurich, Canton of Zurich, CH-8091

Other trials in Switzerland

About this study

Official title: Radiochemotherapy +/- Durvalumab for Locally-advanced Anal Carcinoma.

The RADIANCE multicenter, randomized phase II trial will assess the efficacy of durvalumab, a PD-L1 immune checkpoint inhibitor, in combination with primary mitomycin C (MMC)/5-fluorouracil (5-FU)-based radiochemotherapy (RCT) in patients with locally-advanced anal squamous cell carcinoma (ASCC).

Read the detailed description

Anal squamous cell carcinomas (ASCC) are increasing in frequency across the developed world. There is a strong rationale for combining the PD-L1 immune checkpoint inhibitor durvalumab with radiochemotherapy (RCT) in patients with ASCC. First, although primary RCT with concurrent mitomycin C and 5-fluorouracil (MMC/5-FU) is the standard treatment for ASCC, the 3-year DFS in patients with locally-advanced disease is only in the range of 60%. Second, approximately 80-90% of patients with ASCC are human papilloma virus (HPV)-positive, which is associated with higher tumor "immunogenicity" in this malignancy that is known to correlate with better response to RCT as well as PD-1/PD-L1 immune checkpoint inhibitors. Also, PD-L1 expression was observed in 33%-62% of patients with locally advanced non-metastatic ASCC that correlated with tumor stage. Third, inhibition of the PD-1/PD-L1 axis showed encouraging responses in recurrent/metastatic ASCC in two phase Ib/II trials. Fourth, several data indicate complementary roles between R(C)T and immunotherapy. Fifth, R(C)T can induce PD-L1 upregulation with resulting dysfunction in CD8+ T-cells, and addition of anti-PD-L1 to R(C)T can overcome T-cell suppression to reinvigorate immune surveillance. First clinical studies have demonstrated promising findings for the combination of RCT and immunotherapies. Thus, based on the above data, RCT combined with durvalumab is expected to be more effective than primary RCT alone. Altogether, the hereby proposed RADIANCE multicenter, randomized phase II trial aims to improve the current standard treatment by incorporating durvalumab to the primary MMC/5-FU-based RCT in patients with locally-advanced ASCC (T2=>4cm Nany, stage IIB-IIIC).

Being tested
Chemotherapy, Radiation, Durvalumab
Keywords
Anal Cancer, Anal Carcinoma, Durvalumab, PD-L1 immune checkpoint inhibitor
Medical subject headings
Anus Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ChemotherapyDrug

    Also called all brands of 5-fluorouracil (5-FU) are allowed, all brands of Mitomycin C (MMC) are allowed

    Patients receive chemotherapy cycles as followed:

    Mitomycin-C 12 mg/m², day 1 (maximum single dose 20 mg) 5-FU: 1000 mg/m² per day, continuous i.v. infusion, on day 1-4 and 29-32

  • RadiationRadiation

    PTV_A (primary tumor): T1-T2<4cm N+: 28 x 1.9 Gy=53.2 Gy, five fractions per week or PTV_A (primary tumor): T2>=4cm, T3-4 Nany: 31 x 1.9 Gy=58.9 Gy, five fractions per week PTV_N (involved node): 28 x 1.8 Gy=50.4 Gy, five fractions per weeks PTV_Elec (elective node): 28 x 1.43 Gy=40.0 Gy, five fractions per week

  • DurvalumabDrug

    Also called PD-L1 inhibitor

    1500 mg, 1h-civ, every 4 weeks (q4w) applied on day -14 (that is 14 days prior to initiation of RCT), day 15 (during RCT), and thereafter q4w (+/- 3d) for a total of 12 doses

Study groups in NCT04230759
Study groupRoleWhat they receive
5FU+Mitomycin CActive comparatorRadiochemotherapy for anal cancer
Receives: Drug: Chemotherapy; Radiation: Radiation
5FU+Mitomycin C+DurvalumabExperimentalRadiochemotherapy with Durvalumab for anal cancer
Receives: Drug: Chemotherapy; Radiation: Radiation; Drug: Durvalumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease-free survival (DFS)

    DFS is defined as the time between randomization and the first of the following events: (a) non-complete clinical response at restaging MRI and proctoscopy, including biopsies of suspicious findings, 26 weeks after initiation of radiochemotherapy, (b) locoregional recurrence after initial complete clinical response (cCR), (c) distant metastases, (d) second primary cancer, or (e) death from any cause, whichever occurs first. Patients without any of these events are censored at the time point of last observation.

    Measured: 3 years

Secondary outcomes (8)

  1. Major adverse events

    Adverse events will be graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0

    Measured: 3 Years

  2. cCR

    Complete clinical response rate assessed 26 weeks after initiation of radiochemotherapy

    Measured: 26 weeks

  3. Overall survival

    Overall survival defined as the time between randomization and death from any cause

    Measured: 3 Years

  4. Colostomy-free survival

    Colostomy-free survival defined as time between randomization and a definitive colostomy for progression, relapse, or complication

    Measured: 3 Years

  5. Cumulative incidence of locoregional recurrence

    Cumulative incidence of locoregional recurrence defined as the incidence of locoregional recurrence form the time of randomization

    Measured: 3 Years

  6. Cumulative incidence of distant recurrence

    Cumulative incidence of distant recurrence defined as the incidence of distant recurrence form the time of randomization

    Measured: 3 Years

  7. Quality of life questionnaires

    Quality of life questionnaire QLQ-C30

    Measured: 3 Years

  8. Quality of life questionnaires

    Quality of life questionnaire QLQ-ANL27

    Measured: 3 Years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jan 2020
  2. Study start7 Jan 2020
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
180 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04230759
Sponsor's protocol ID
RADIANCE
Other IDs
2018-003005-25, 70113615, ESR-17-13077, 2024-513914-36-00, 2018
Acronym
RADIANCE
Status last verified
Aug 2026
First submitted
8 Jan 2020
Last updated
14 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Chemotherapy, Radiation and Durvalumab in people with Anal Cancer and Anal Carcinoma, run by Goethe University at 25 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 14 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in Germany, Austria, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease-free survival (DFS) (time frame: 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04230759.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2026.

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