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

NCT04230759 | Active Not Recruiting Phase 2 DMC

• 5 other identifiers: RADIANCE2018-003005-2570113615ESR-17-130772024-513914-36-00
• Study Type: interventional
• Target: 180
• Locations: 3 countries
• Sites: 25

Brief 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).

Conditions

Anal Cancer; Anal Carcinoma; Anal Cancer Stage III; Anal Cancer Stage II

Keywords

Anal Cancer; Anal Carcinoma; Durvalumab; PD-L1 immune checkpoint inhibitor

Outcome Measures

Primary Outcomes (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.

  3 years

Secondary Outcomes (8)

• Major adverse events

  3 Years

• cCR

  26 weeks

• Overall survival

  3 Years

• Colostomy-free survival

  3 Years

• Cumulative incidence of locoregional recurrence

  3 Years

Study Arms (2)

5FU+Mitomycin C

ACTIVE COMPARATOR

Radiochemotherapy for anal cancer

Drug: Chemotherapy; Radiation: Radiation

5FU+Mitomycin C+Durvalumab

EXPERIMENTAL

Radiochemotherapy with Durvalumab for anal cancer

Drug: Chemotherapy; Radiation: Radiation; Drug: Durvalumab

Interventions

Chemotherapy DRUG

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

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

5FU+Mitomycin C; 5FU+Mitomycin C+Durvalumab

Radiation RADIATION

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

5FU+Mitomycin C; 5FU+Mitomycin C+Durvalumab

Durvalumab DRUG

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

Also known as: PD-L1 inhibitor

5FU+Mitomycin C+Durvalumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• Goethe University: lead

Study Sites (25)

Univeritätsklinik für Strahlentherapie-Radioonkologie

Graz, 8036, Austria

Location

Institut für Radioonkologie und Strahlentherapie

Darmstadt, Darmstadt, 64283, Germany

Location

Klinik und Poliklinik für Strahlentherapie und Radioonkologie

Dresden, Dresden, 01307, Germany

Location

Klinik für Strahlenheilkunde, Universitätsklinikum Freiburg

Freiburg im Breisgau, Freiburg, 79106, Germany

Location

Klinik und Poliklinik für Strahlentherapie

Essen, Hesse, 45122, Germany

Location

UKSH Campus Kiel

Kiel, Kiel, 24105, Germany

Location

Universitätsklinikum Leipzig

Leipzig, Leipzig, 04103, Germany

Location

Universitätsklinikum Magdeburg

Magdeburg, Magdeburg, 39120, Germany

Location

Universitätsmedizin Mainz

Mainz, Mainz, 55131, Germany

Location

Uniklinikum Marburg

Marburg, Marburg, 35043, Germany

Location

Kliniken Maria Hilf GmbH Mönchengladbach

Mönchengladbach, Mönchengladbach, 41063, Germany

Location

LMU Klinikum der Universität München

München, München, 81377, Germany

Location

Technische Universität München

München, München, 81675, Germany

Location

Universitätsklinikum Regensburg

Regensburg, Regensburg, 93053, Germany

Location

Universitätsklinikum Rostock

Rostock, Rostock, 18059, Germany

Location

Radioonkologie und Strahlentherapie

Berlin, State of Berlin, 12203, Germany

Location

Universitätsklinik Tübingen

Tübingen, Tübingen, 72076, Germany

Location

Universitätsklinikum Würzburg

Würzburg, Würzburg, 97080, Germany

Location

OnkoLibri GbR

Berlin, 14195, Germany

Location

University Hospital Goethe University Frankfurt

Frankfurt, 60590, Germany

Location

Universitätsmedizin Göttingen

Goettigen, 37075, Germany

Location

Asklepios Klinik Altona

Hamburg, 22763, Germany

Location

Hospital Barmherzige Brüder

Regensburg, 93049, Germany

Location

Klinikum Stuttgart

Stuttgart, 70174, Germany

Location

UniversitätsSpital Zürich

Zurich, Canton of Zurich, CH-8091, Switzerland

Location

MeSH Terms

Conditions

Anus Neoplasms

Interventions

Drug Therapy; Fluorouracil; Radiation; durvalumab; Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Physical Phenomena; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PD MD

Study Record Dates

• First Submitted: January 8, 2020
• First Posted: January 18, 2020
• Study Start: January 7, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); CH (1); DE (23)