E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
classical and endemic Kaposi's patient with progressive disease, |
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E.1.1.1 | Medical condition in easily understood language |
Kaposi's sarcoma |
Maladie de KAPOSI |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10023284 |
E.1.2 | Term | Kaposi's sarcoma |
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 main objective is to assess whether pembrolizumab is clinically inactive (partial+complete response probability ?0<5%) or truly active (partial+complete response probability ?1>30%) in classic and endemic Kaposi's sarcoma, using the Simon's 2 stage Optimal Design. |
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E.2.2 | Secondary objectives of the trial |
- to assess the safety profile of pembrolizumab in classic and endemic Kaposi's sarcoma, - to characterize the efficacy of pembrolizumab related to pharmacodynamics assessment
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Classic or endemic histologically confirmed KS 2.Progressive disease 3.KS with more than 10 lesions or involving more than one limb segment or with involvement >3% body surface 4.KS with at least 4 lesions>ou = 5mm 5.KS with at least 1 other cutaneous tumor available for repeated pharmacodynamics evaluation and be willing to provide tissue from cutaneous biopsy of a tumor lesion 6.At least 4 weeks washout for all KS specific therapies including chemotherapy and immunotherapy such as Interferon In order to be eligible for participation in this trial, the subject must: "Be willing and able to provide written informed consent for the trial. - Female subject of childbearing potential should have a negative serum pregnancy within 72 hours prior to receiving the first dose of study medication, and a negative urine pregnancy test prior to receiving each other dose. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. "Be 18 years of age on day of signing informed consent. "Have a performance status of 0 or 1 on the ECOG Performance Scale. "Have a health insurance
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E.4 | Principal exclusion criteria |
1.Has a known history of organ transplantation or HIV (HIV 1/2 antibodies detected at selection) 2.Is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. 4.Previously received treatments with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4 antibody or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways. 5.Has a known history of active infectious hepatitis, type B (HBsAg detected) or C (HCV RNA detected) or active TB (Bacillus Tuberculosis). 6.Has an active infection requiring systemic therapy. 7.Has hypersensitivity to pembrolizumab or any of its excipients. 8.Has had a prior anti-cancer monoclonal antibody (mAb) within last 4 weeks or who has not recovered (i.e., > Grade 1 at selection) from adverse events due to agents administered more than 4 weeks earlier. 9.Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 3 weeks prior to study Day 1 or who has not recovered (i.e., > Grade 1 at selection) from adverse events due to a previously administered agent. Note: Subjects with ? Grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. 10.Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. 11.Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patients with vitiligo, type I diabetes mellitus, hypothyroidism, psoriasis non requiring systemic treatment are permitted to enroll. 12.Has active non-infectious pneumonitis or known history of non-infectious pneumonitis that required steroids, severe pulmonary disease or hypoxia 13.Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 14.Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, or not willing to use adequate contraceptive methods from study Visit 1 throughout the study period up to 120 days after the last dose of study therapy (refer to Section 7.4). 15.Has received a live vaccine within 30 days prior to the first dose of trial treatment . Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, BCG, and typhoid vaccine (refer to Section 7.2).
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the Best Overall Response Rate (BORR) defined by the occurrence of complete response or partial response following ACTG criteria recorded from the start of treatment until 6 months or the beginning of any other specific systemic therapy for KS if it occurs before 6 months. |
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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) Efficacy endpoints
1.Best overall response rate according to Physical Global Assessment (PGA) score until 6 months or the beginning of any other specific systemic therapy for KS if it occurs before 6 months. 2.Response rate at Month 3 and Month 6 according to ACTG and PGA criteria 3.Response rate on number of lesions at Month 3, Month 6 and at best response as defined following ACTG criteria 4.Response rate on the size of target lesions at Month 3, Month 6 and at best response as defined following ACTG criteria 5.Response rate on tumor infiltration of target lesions at Month 3, Month 6 and at best response as defined following ACTG criteria 6.Response rate on lymphedema (circumference, scale of 0 (absence) to 3 (painful or oozing)) at Month 3, Month 6 and at best response as defined following ACTG criteria 7.Time to response defined as the time to first response recorded from the start of treatment 8.Time to progression
(2) Safety endpoints Safety will be assessed in terms of drug toxicity evaluated by clinic and on laboratory parameters, and scored according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (http://ctep.cancer.gov/reporting/ctc.html) during all the study.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.7 | Pharmacodynamic | No |
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 | No |
E.8.1.1 | Randomised | No |
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 | No |
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 | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |