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Pembrolizumab Compared to Standard of Care Observation in Treating Patients With Completely Resected Stage I-III Merkel Cell Cancer

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ClinicalTrials.gov Identifier: NCT03712605
Recruitment Status : Recruiting
First Posted : October 19, 2018
Last Update Posted : February 12, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

October 17, 2018
October 19, 2018
February 12, 2019
October 1, 2018
October 31, 2023   (Final data collection date for primary outcome measure)
  • Recurrence free survival (RFS) [ Time Frame: From randomization until disease recurrence or death from any cause; assessed up to 4.5 years ]
    An intention-to-treat (ITT) analysis using the stratified log-rank test will be performed to compare overall survival (OS) and RFS between the two arms.
  • OS [ Time Frame: From randomization until death, assessed up to 4.5 years ]
    An ITT analysis using the stratified log-rank test will be performed to compare OS and RFS between the two arms.
Same as current
Complete list of historical versions of study NCT03712605 on ClinicalTrials.gov Archive Site
  • Impact of radiation therapy on RFS [ Time Frame: Up to 4.5 years ]
    RFS in each arm will be evaluated by radiation treatment status (radiation versus [vs.] no radiation therapy). The analysis will be a planned post-hoc analysis with primary goal of examining whether use of post-operative radiation therapy is associated with RFS. Cox multivariate models for RFS will be developed to evaluate the impact of radiation therapy while adjusting for pembrolizumab treatment and clinical/ pathological factors. The treatment fields and dose data will also be included in the Cox model as covariates. Secondary analyses for radiation therapy (RT) will examine factors associated with use of post-operative RT. Multivariate logistic regression models (radiation therapy vs. no radiation therapy) will be developed to evaluate the associations with demographic, clinical/pathologic, and treatment-related factors and pembrolizumab treatment.
  • Impact of radiation therapy on OS [ Time Frame: Up to 4.5 years ]
    OS in each arm will be evaluated by radiation treatment status (radiation vs. no radiation therapy). The analysis will be a planned post-hoc analysis with primary goal of examining whether use of post-operative radiation therapy is associated with OS. Cox multivariate models for OS will be developed to evaluate the impact of radiation therapy while adjusting for pembrolizumab treatment and clinical/ pathological factors. The treatment fields and dose data will also be included in the Cox model as covariates. Secondary analyses for radiation therapy will examine factors associated with use of post-operative RT. Multivariate logistic regression models (radiation therapy vs. no radiation therapy) will be developed to evaluate the associations with demographic, clinical/pathologic, and treatment-related factors and pembrolizumab treatment.
  • Impact of radiation therapy on distant metastasis free survival (DMFS) [ Time Frame: From randomization to distant metastasis, assessed up to 4.5 years ]
    DMFS will be evaluated by treatment arms. If there is no distant metastasis, cases will be censored at the time of last assessment.
  • Incidence of adverse events per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [ Time Frame: Up to 4.5 years ]
    Adverse events from each arm will be summarized and compared using the Fisher's exact test.
Same as current
Not Provided
Not Provided
 
Pembrolizumab Compared to Standard of Care Observation in Treating Patients With Completely Resected Stage I-III Merkel Cell Cancer
A Phase III Randomized Trial Comparing Adjuvant MK-3475 (Pembrolizumab) to Standard of Care Observation in Completely Resected Merkel Cell Carcinoma
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. 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.

PRIMARY OBJECTIVES:

I. To compare overall survival (OS) and recurrence free survival (RFS) as co-primary endpoints across the two arms.

SECONDARY OBJECTIVES:

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 courses in the absence of disease progression or unacceptable toxicity. Patients may also undergo standard of care radiation therapy within 14 days of day 1, course 1.

ARM B: Patients receive standard of care observation for 17 courses. Patients may also undergo standard of care radiation therapy within 14 days of day 1, course 1.

After completion of study treatment, patients are followed up every 6 months for 4 years.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • 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
  • Resected Mass
  • Other: Best Practice
    Receive standard of care observation
    Other Names:
    • standard of care
    • standard therapy
  • Biological: Pembrolizumab
    Given IV
    Other Names:
    • Keytruda
    • Lambrolizumab
    • MK-3475
    • SCH 900475
  • Radiation: Radiation Therapy
    Undergo radiation therapy
    Other Names:
    • Cancer Radiotherapy
    • Irradiate
    • Irradiated
    • irradiation
    • Radiation
    • Radiotherapeutics
    • RADIOTHERAPY
    • RT
    • Therapy, Radiation
  • Experimental: Arm A (pembrolizumab, radiation therapy)
    Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity. Patients may also undergo standard of care radiation therapy within 14 days of day 1, course 1.
    Interventions:
    • Biological: Pembrolizumab
    • Radiation: Radiation Therapy
  • Active Comparator: Arm B (standard of care observation, radiation therapy)
    Patients receive standard of care observation for 17 courses. Patients may also undergo standard of care radiation therapy within 14 days of day 1, course 1.
    Interventions:
    • Other: Best Practice
    • Radiation: Radiation Therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
500
Same as current
October 31, 2023
October 31, 2023   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status: 0, 1, or 2 (Those patients who are wheel chair bound due to congenital or traumatic events more than one year before the diagnosis of Merkel cell carcinoma may be considered.)
  • 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, if receiving MK-3475 (pembrolizumab) or radiation therapy, and sexually active males must use an accepted and effective method of contraception or to abstain from sex from time of registration, while on study treatment, and continue for 120 days after the last dose of study treatment.
  • 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 negative margins.
  • Patients with all macroscopic Merkel cell carcinoma (either identified by physical exam or imaging) have been completely resected by surgery within 8 weeks before enrollment.
  • All patients must have disease-free status documented by a complete physical examination and conventional imaging studies within 4 weeks prior to randomization.
  • Patient must have no currently present metastases (as confirmed by standard imaging studies).
  • Patient must have no previous systemic therapy or radiation therapy for Merkel cell carcinoma.
  • Patients with inoperable disease who have received radiation are not eligible.
  • 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 103/uL (within 4 weeks prior to randomization).
  • Hemoglobin >= 8 g/dL (>= 80 g/L; may be transfused) (within 4 weeks prior to randomization).
  • Creatinine =< 2.0 x upper limit of normal (ULN) (within 4 weeks prior to randomization).
  • Aspartate aminotransferase (AST)/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 eligible.
  • 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) 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.
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
United States
 
 
NCT03712605
NCI-2018-02217
NCI-2018-02217 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
EA6174 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
EA6174 ( Other Identifier: CTEP )
U10CA180820 ( U.S. NIH Grant/Contract )
No
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Brian R Gastman ECOG-ACRIN Cancer Research Group
National Cancer Institute (NCI)
October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP