Trial Title:
Chemo-immunotherapy in Patients With Resectable Merkel Cell Carcinoma Prior to Surgery
NCT ID:
NCT05594290
Condition:
Merkel Cell Carcinoma
Conditions: Official terms:
Carcinoma, Merkel Cell
Carcinoma
Etoposide
Conditions: Keywords:
Merkel Cell Carcinoma
Chemo-immunotherapy
Retifanlimab
Surgery
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Phase 2, multicentre, single-arm, open-label clinical trial
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Retifanlimab
Description:
Retifanlimab i.v. 500 mg day 1
Arm group label:
Preoperative arm
Intervention type:
Drug
Intervention name:
Cisplatin
Description:
Cisplatin 25 mg/sqm i.v. day 1, 2 (recommended platinum agent) or carboplatin AUC 4 i.v.,
day 1 (in patients unsuited or unfit for cisplatin)
Arm group label:
Preoperative arm
Intervention type:
Drug
Intervention name:
Etoposide
Description:
Etoposide 100 mg/sqm iv. day 1, 2, 3
Arm group label:
Preoperative arm
Summary:
This is a window-of-opportunity study for patients with resectable Merkel Cell Carcinoma.
The aim of this study is to test the activity of a course of chemo-immunotherapy followed
by surgery in patients with operable Merkel cell carcinoma.
Participants will receive one cycle of retifanlimab plus platinum-etoposide chemotherapy
prior to their scheduled surgery.
Detailed description:
This is a multicenter, single-arm, open-label, phase 2 Window-of-opportunity trial to
assess the activity of 1 cycle of preoperative retifanlimab plus platinum-etoposide
chemo-immunotherapy regimen in patients with resectable MCC (stage IIA-III).
Patients who meet the eligibility criteria will be treated with one cycle of
chemo-immunotherapy.
After receiving the short-course preoperative chemo-immunotherapy study regimen, patients
will undergo standard radical surgery between weeks 5 and 6 from enrollment. After
surgery, patients will receive adjuvant radiation therapy, if indicated, and afterwards,
standard follow up will be started as per clinical practice and guidelines.
Baseline radiological assessments will include chest/abdomen/pelvis CT scan with contrast
and CT scan of additional anatomical sites should be performed if the primary tumor is
elsewhere.
The enrollment of patients will be temporary interrupted after the inclusion of first 6
patients in the trial. When 6 patients will complete the study treatment, a Safety
Monitoring Committee will complete a safety evaluation.
The enrollment will then resume only if the study treatment combination is judged
feasible and no major safety concerns arise.
The study primary endpoint will be the pathological complete response rate or pCR rate,
defined as the percentage of patients, relative to the total of enrolled subjects in the
intention-to-treat population, who will achieve a pathological complete response, as per
central pathological review.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Signed informed consent.
2. Subjects must be 18 years old or older.
3. ECOG performance status of 0 to 1.
4. Histologically confirmed diagnosis of MCC amenable for radical surgery as defined by
local or institutional surgical practices, based on multidisciplinary team
assessment. Subjects must have one of the following stages of disease:
1. Stage IIA - IIB- III (according to the AJCC staging system 8th edition)
2. Local/Regional recurrent disease after primary surgery, as defined as total
disease burden ≥ 1 cm diameter amenable for a radical intent surgery. Note:
nodal disease without any known primary (in absence of a primary cutaneous site
after a complete diagnostic/staging work-up including chest/abdomen CT-scan,
dermatologic clinical examination and 18F-FDG-PET scan) can be enrolled and
will be considered as Stage III.
5. Able to provide archival FFPE tumor samples (if collected within three months from
study enrollment) or have a tumor amenable to pre-treatment biopsy. Excisional,
incisional, or core- needle samples are acceptable. Fine needle aspirates are not
allowed.
6. No prior systemic treatment or neoadjuvant radiation therapy.
7. Adequate bone marrow function characterized by the following at screening:
1. Platelets ≥ 100 × 109/L
2. Absolute neutrophil count (ANC) ≥1.5 x 109/L
3. Hemoglobin ≥ 9.0 g/dL
8. Adequate renal function characterized by serum creatinine ≤ 1.5 × upper limit of
normal (ULN) OR calculated by Cockroft-Gault formula or directly measured creatinine
clearance ≥ 60 mL/min at screening for subject receiving cisplatin OR creatinine
clearance ≥ 50 mL/min at screening for subject receiving carboplatin.
9. Adequate hepatic function characterized by the following at screening:
1. Serum total bilirubin ≤ 1.5 × ULN and < 2 mg/dL. Note: Subjects with Serum
total bilirubin ≥ 1.5 × ULN and conjugated bilirubin ≤ ULN or < 40% of total
bilirubin are allowed.
2. AST (SGOT) and/or ALT (SGPT) <2.5 x UNL.
10. Men must agree to take appropriate precautions to avoid fathering children (with at
least 99% certainty) from screening through 6 months after the administration of
study treatment and must refrain from donating sperm during this period. Permitted
methods that are at least 99% effective in preventing pregnancy (see Appendix A)
should be communicated to the participants and their understanding confirmed.
11. Women of childbearing potential must have a negative serum pregnancy test at
screening and before the first dose on Day 1 and must agree to take appropriate
precautions to avoid pregnancy (with at least 99% certainty) from screening through
180 days after the administration of any study drug. Permitted methods that are at
least 99% effective in preventing pregnancy should be communicated to the
participants and their understanding confirmed.
12. Women of non-childbearing potential (i.e. surgically sterile with a hysterectomy
and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea and at least 50 years of
age) are eligible.
13. Willingness to comply with scheduled visits, treatment plan, laboratory tests and
other study procedures.
Exclusion Criteria:
1. Prior systemic therapy for MCC, including chemotherapy and prior PD-1 or
PD-L1-directed therapy.
2. Primary tumor or nodal metastasis fixed to the carotid artery, skull base or
cervical spine.
3. Treatment with anticancer drugs, radiation therapy or participation in another
interventional clinical study within 28 days before the first administration of
study drug.
4. Distant metastases at any site.
5. Any known additional malignancy that is progressing or requires active treatment, or
history of other malignancy within 2 years of study entry except for cured basal
cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate
intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or
indolent malignancy.
6. Impaired cardiovascular function or clinically significant cardiovascular diseases,
including any of the following:
1. History of acute myocardial infarction, acute coronary syndromes (including
unstable angina, coronary artery bypass graft [CABG], coronary angioplasty or
stenting) ≤ 6 months prior to start of study treatment;
2. Symptomatic congestive heart failure (i.e., Grade 2 or higher), history or
current evidence of clinically significant cardiac arrhythmia and/or conduction
abnormality ≤ 6 months prior to start of study treatment, except atrial
fibrillation and paroxysmal supraventricular tachycardia.
7. History of autoimmune disease including but not limited to myasthenia gravis,
myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,
inflammatory bowel disease, vascular thrombosis associated with antiphospholipid
syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome,
multiple sclerosis, vasculitis, or glomerulonephritis.
Note: Subjects with a history of autoimmune-related hypothyroidism on a stable dose
of thyroid replacement hormone may be eligible. Subjects with controlled type I
diabetes mellitus on a stable insulin regimen, vitiligo or psoriasis not requiring
systemic treatment may be eligible.
8. History of chronic conditions (i.e. COPD) requiring systemic immune-suppression in
excess of physiologic maintenance doses of corticosteroids (> 10 mg of prednisone or
equivalent).
9. Evidence of interstitial lung disease or active noninfectious pneumonitis.
10. History of organ transplant, including allogeneic stem cell transplantation.
11. History or current evidence of any condition, therapy or laboratory abnormality that
might interfere with the subject's participation to the study or is not in the best
interest of the subject to participate, in the opinion of the treating investigator.
12. Know active hepatitis B [positive HBV surface antigen (HBsAg) result] or 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
13. Known uncontrolled HIV infection. HIV-positive patients are eligible if their CD4+
cell count amounts to 300 cells per μL or more; HIV viral load must be undetectable
per standard of care assay, and they have to be compliant with antiretroviral
treatment.
14. Active infections requiring systemic therapy, or systemic antibiotic use up to 10
days before Cycle 1 Day 1.
15. Live vaccines within 28 days prior to and for a duration of 90 days after the
administration of study drug are forbidden.
Note: Examples of live vaccines include, but are not limited to, the following:
measles, mumps, rubella, chickenpox/zoster, yellow fever, rabies, Bacillus Calmette
Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally
killed virus vaccines and are allowed. COVID-19 vaccine is allowed, with an interval
of 2 days before and 2 days after the administration of study drugs;
16. Known hypersensitivity to platinum, etoposide or any of the excipients that cannot
be controlled with standard measures (eg, antihistamines, corticosteroids).
17. Known allergy or hypersensitivity to any component of the study drug formulation.
18. Subjects who lack the ability or are unlikely, in the opinion of the investigator,
to comply with the Protocol requirements.
19. Subjects who are pregnant or breastfeeding.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
Address:
City:
Milan
Zip:
20133
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Federica Morano, MD
Phone:
+39 0223903842
Email:
federica.morano@istitutotumori.mi.it
Contact backup:
Last name:
Federica Palermo
Phone:
+39 0223903835
Email:
mercury.study@istitutotumori.mi.it
Start date:
December 7, 2022
Completion date:
November 2026
Lead sponsor:
Agency:
Gruppo Oncologico del Nord-Ovest
Agency class:
Other
Source:
Gruppo Oncologico del Nord-Ovest
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05594290
