Pembrolizumab Compared to Standard of Care Observation in Treating Patients With Completely Resected Stage I-III Merkel Cell Cancer, STAMP Study
This phase III trial studies how well pembrolizumab works compared to standard of care observation in treating patients with stage I-III Merkel cell cancer that has been completely removed by surgery (resected). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
- Pathologic Stage I Merkel Cell Carcinoma AJCC v8
- Pathologic Stage II Merkel Cell Carcinoma AJCC v8
- Pathologic Stage IIA Merkel Cell Carcinoma AJCC v8
- Pathologic Stage IIB Merkel Cell Carcinoma AJCC v8
- Pathologic Stage III Merkel Cell Carcinoma AJCC v8
- Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8
- Pathologic Stage IIIB Merkel Cell Carcinoma AJCC v8
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Accepts Healthy Volunteers
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status: 0,
1, or 2 (However, those patients with a performance state of 3 because they are wheel
chair bound due to congenital or traumatic events more than one year before the
diagnosis of Merkel cell carcinoma are eligible).
- Women must not be pregnant or breast-feeding due to the unknown effects of the study
drug in this setting. All women of childbearing potential must have a blood test or
urine study within 2 weeks prior to registration to rule out pregnancy. A female of
childbearing potential is any woman, regardless of sexual orientation or whether they
have undergone tubal ligation, who meets the following criteria: 1) has achieved
menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy;
or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does
not rule out childbearing potential) for at least 24 consecutive months (i.e., has had
menses at any time in the preceding 24 consecutive months).
- Women of childbearing potential, and sexually active males, on Arm A MK-3475
(pembrolizumab must use accepted and effective method(s) of contraception or abstain
from sex from time of registration, while on study treatment, and continue for 120
days after the last dose of study treatment. For patients on Arm B only receiving
radiation therapy, contraception use should be per institutional standard.
- Patient must have a histological confirmation of diagnosis of Merkel cell carcinoma
(MCC), pathologic stages (American Joint Committee on Cancer [AJCC] version 8) I-IIIb.
- Stage I patients with negative sentinel lymph node biopsy are ineligible.
Patients who have a positive biopsy or for whom no biopsy was done are eligible.
- Patients with distant metastatic disease (stage IV) are not eligible.
- The primary tumor must have grossly negative margins. (Microscopically positive
margins are allowed).
- Cancers of unknown primary that have regional disease only can be included.
- Complete nodal dissection is not required for eligibility.
- Patients with all macroscopic Merkel cell carcinoma (either identified by physical
exam or imaging) have been completely resected by surgery within 16 weeks before
- All patients must have disease-free status documented by a complete physical
examination and conventional imaging studies within 8 weeks prior to registration.
- Patient may not have a history of distant metastatic disease.
- NOTE: Loco-regional recurrent disease is acceptable, as long as this is not
metastatic (prior surgery with or without radiation therapy is acceptable).
- For patients with initial presentation of Merkel cell carcinoma, patient must have no
previous systemic therapy or radiation therapy prior to surgery for Merkel cell
carcinoma and cannot have completed adjuvant radiation therapy for Merkel cell
carcinoma more than 6 weeks prior to registration. Patients actively undergoing
radiation therapy or having completed adjuvant radiation therapy within 6 weeks of
registration are eligible, as long as resection date is within 16 weeks of
- White blood count >= 2000/uL (within 4 weeks prior to randomization).
- Absolute neutrophil count (ANC) >= 1000/uL (within 4 weeks prior to randomization).
- Platelets >= 75 x 10^3/uL (within 4 weeks prior to randomization).
- Hemoglobin >= 8 g/dL (>= 80 g/L; may be transfused) (within 4 weeks prior to
- Creatinine =< 2.0 x upper limit of normal (ULN) (within 4 weeks prior to
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
(within 4 weeks prior to randomization).
- Total bilirubin =< 2.0 x ULN, (except patients with Gilbert's syndrome, who must have
a total bilirubin less than 3.0 mg/dL) (within 4 weeks prior to randomization).
- Patients who are human immunodeficiency virus (HIV)+ with undetectable HIV viral load
are eligible provided they meet all other protocol criteria for participation.
- Patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are
eligible provided viral loads are undetectable. Patients on suppressive therapy are
- Patients must not be on active immunosuppression, have a history of life threatening
virus, have had other (beside non-melanoma skin cancers, or recent indolent cancers
e.g.: resected low grade prostate cancer) invasive cancer diagnoses in the last two
years, or have had immunotherapy of any kind within the last 2 years.
- Patients must not have a history of (non-infectious) pneumonitis that required
steroids or has current pneumonitis.
- Operative notes from patient's surgical resection must be accessible.
- Phase 3
- Study Type
- Intervention Model
- Parallel Assignment
- Primary Purpose
- None (Open Label)
Arm A (pembrolizumab, radiation therapy)
|Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo standard of care radiation therapy within 14 days of day 1, cycle 1.||
Arm B (standard of care observation, radiation therapy)
|Patients receive standard of care observation every 3 months for 1 year, and then every 6 months for 5 years. Patients may also undergo standard of care radiation therapy within 14 days of day 1, cycle 1.||
- National Cancer Institute (NCI)
I. To compare overall survival (OS) and recurrence free survival (RFS) as co-primary endpoints across the two arms.
I. To evaluate adverse events. II. To evaluate distant metastasis free survival (DMFS). III. To evaluate the impact of radiation on clinical outcomes (OS, RFS, DMFS).
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo standard of care radiation therapy within 14 days of day 1, cycle 1.
ARM B: Patients receive standard of care observation every 3 months for 1 year, and then every 6 months for 5 years. Patients may also undergo standard of care radiation therapy within 14 days of day 1, cycle 1.
After completion of study treatment, patients are followed up every 6 months for 5 years.