E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
metastatic squamous cell carcinoma of the anal canal |
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E.1.1.1 | Medical condition in easily understood language |
metastatic squamous cell carcinoma of the anal canal |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10055096 |
E.1.2 | Term | Anal cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of this trial is to assess anti-tumour activity of BI 754091 as a monotherapy and of BI 754091 in combination with BI 836880 in patients with unresectable or metastatic squamous cell carcinoma of the anal canal who progressed on or after chemotherapy. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Signed and dated written Informed Consent Form (ICF) in accordance with ICH-GCP and local legislation prior to admission to the trial.
- Patients ≥18 years of age or over the legal age of consent in countries where that is greater than 18 years at the time of signature of the ICF.
- Patients must have histologically or cytologically documented surgically unresectable locally-advanced or metastatic SCCA.
- Patients with loco-regional anal cancer as initial diagnosis must have unresectable progressive locally advanced or metastatic SCCA after failure of at least one line (but not more than two lines) of previous systemic treatment unless ineligible for or intolerant to this systemic therapy.
- Patients with metastatic anal cancer as initial diagnosis must have failed one line of previous systemic treatment (chemotherapy ± radiotherapy) for the metastatic anal cancer unless ineligible for or intolerant to this systemic treatment.
- All patients must have at least one measurable lesion according to RECIST v1.1 criteria.
- Eastern Cooperative Oncology Group performance status [ECOG, R01-0787] score 0 to 1
- Patients must be willing to allow PD-L1 status assessment by one of following options. Preference is given to fresh tumour biopsy sample collection at baseline before receiving first trial medication. In case a fresh tumour biopsy cannot be obtained (e.g. inaccessible lesions or patient safety concern), archival tissue will be requested. If neither is available any previous historical information regarding PD-L1 status should be collected via eCRF.
- Further criteria apply. |
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E.4 | Principal exclusion criteria |
- Current or prior treatment with any systemic anti-cancer therapy or any investigational product (or device) either within 28 days or less than 5 half-lives (whichever is shorter) before start of trial treatment.
- Major injuries and/or surgery or bone fracture within 4 weeks of start of treatment, or planned surgical procedures during the trial period.
- Significant cardiovascular/cerebrovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within past 6 months, congestive heart failure > NYHA II).
- Known inherited predisposition to bleeding or to thrombosis in the opinion of the investigator.
- History of severe hemorrhagic or thromboembolic event in the past 12 months (excluding central venous catheter thrombosis and peripheral deep vein thrombosis).
- Patients who require full-dose anticoagulation (according to local guidelines). No Vitamin K antagonist and other anticoagulation allowed; LMWH and acetylsalicylic acid (ASA) allowed only for prevention not for curative treatment.
- Prior treatment with anti-PD-1, anti-PD-L1, or anti CTLA-4 treatment
- Prior treatment with any antiangiogenic agent (e.g. bevacizumab, cediranib, aflibercept, vandetanib, XL-184, sunitinib, etc.)
- Further criteria apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Objective response (OR) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1) Duration of objective response (DoR)
2) Progression-free survival (PFS)
3) Overall survival (OS)
4) Disease control (DC)
5) Adverse events (AEs) from the time of treatment initiation until the end of the REP
6) Drug related AEs from the time of treatment initiation until the end of the REP
7) Drug related AEs leading to dose reduction of BI 836880 and/or discontinuation of study treatment |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) up to 3.5 years
2) up to 3.5 years
3) up to 3.5 years
4) up to 3.5 years
5) up to 3.5 years
6) up to 3.5 years
7) up to 3.5 years |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
BI 754091 mono is the comparator, which is compared against BI 836880/BI 754091 combination |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 84 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Chile |
Croatia |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Greece |
Hungary |
Israel |
Italy |
Japan |
Korea, Republic of |
Latvia |
Mexico |
Netherlands |
Norway |
Peru |
Poland |
Portugal |
Romania |
Russian Federation |
Serbia |
Slovakia |
Spain |
Sweden |
Taiwan |
Thailand |
Ukraine |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |