Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pembrolizumab Versus Placebo Following Surgery and Radiation in Participants With Locally Advanced Cutaneous Squamous Cell Carcinoma (MK-3475-630/KEYNOTE-630)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03833167
Recruitment Status : Recruiting
First Posted : February 6, 2019
Last Update Posted : October 17, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
This is a randomized, double-blind, study that compares pembrolizumab with placebo given as adjuvant therapy in participants with high-risk locally advanced cutaneous squamous cell carcinoma (LA cSCC) that have undergone surgery with curative intent in combination with radiotherapy. The primary hypothesis is that pembrolizumab is superior to placebo in increasing recurrence free survival (RFS).

Condition or disease Intervention/treatment Phase
Carcinoma, Squamous Cell Biological: Pembrolizumab 400 mg Drug: Placebo Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 570 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate Pembrolizumab Versus Placebo as Adjuvant Therapy Following Surgery and Radiation in Participants With High-risk Locally Advanced Cutaneous Squamous Cell Carcinoma (LA cSCC) (KEYNOTE-630)
Actual Study Start Date : April 1, 2019
Estimated Primary Completion Date : April 6, 2026
Estimated Study Completion Date : April 6, 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Pembrolizumab
Participants receive 400 mg pembrolizumab by intravenous (IV) infusion administered on Day 1 of each 42-day cycle (Q6W) for up to 9 cycles. Participants that complete 9 cycles of pembrolizumab and experience biopsy-proven-disease recurrence may be eligible to receive up to 18 additional cycles of pembrolizumab in an open-label design.
Biological: Pembrolizumab 400 mg
Administered by IV infusion on Day 1 of each 42-day cycle
Other Names:
  • KEYTRUDA®
  • MK-3475

Placebo Comparator: Placebo
Participants receive placebo by IV infusion administered on Day 1 of each 42-day cycle (Q6W) for up to 9 cycles. Participants treated with placebo who experience biopsy-proven-disease recurrence may be eligible to receive up to 18 cycles of pembrolizumab in an open-label design.
Drug: Placebo
Administered by IV infusion on Day 1 of each 42-day cycle




Primary Outcome Measures :
  1. Recurrence-Free Survival (RFS) as Assessed by the Investigator and Confirmed by Biopsy [ Time Frame: Up to approximately 60 months ]
    RFS was defined as the time between the date of randomization to the date of first local or regional recurrence of the index lesion, distant metastasis, or death due to any cause; whichever occurred first.


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to approximately 60 months ]
    OS is the time from randomization to death due to any cause.

  2. Change From Baseline in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score [ Time Frame: Baseline and up to approximately 60 months ]
    Change from baseline in the score of EORTC QLQ-C30 is reported. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire, which contains 30 items and measures 5 functioning dimensions (physical, role, emotional, cognitive, and social), 3 symptom items (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact), and a global health and QoL scale. Scores ranged from 0 -100. For functional and global quality of life (QoL) scales, higher scores meant a better level of function. For symptom-oriented scales, a higher score meant more severe symptoms and a decrease in QoL.

  3. Change From Baseline in Physical Functioning Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 1-5 Score [ Time Frame: Baseline and up to approximately 60 months ]
    Change from baseline in the score of EORTC QLQ-C30 Items 1-5 is reported. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. Higher scores meant a better level of function.

  4. Percentage of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 63 months ]
    An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The percentage of participants who experience at least one AE will be presented.

  5. Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) [ Time Frame: Up to approximately 38 months ]
    An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The percentage of participants who discontinue study treatment due to an AE will be presented.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has histologically confirmed cutaneous squamous cell carcinoma (cSCC) as the primary site of malignancy (metastatic skin involvement from another primary cancer or from an unknown primary cancer is not permitted)
  • Has histologically confirmed LA cSCC with ≥1 high-risk feature(s) as the primary site of malignancy
  • Has undergone complete macroscopic resection of all known cSCC disease with or without microscopic positive margins. For those participants with residual microscopic positive margin involvement, confirmation that additional re-excision is not possible must be provided
  • Has completed adjuvant radiotherapy (RT) for LA cSCC with last dose of RT ≥4 weeks and ≤16 weeks from randomization
  • Has completed at least 45 Gray (Gy) of adjuvant RT for LA cSCC prior to study entry
  • Is disease free as assessed by the investigator with complete radiographic staging assessment ≤28 days from randomization
  • Is not pregnant or breastfeeding
  • Is not a woman of childbearing potential (WOCBP)
  • Has a negative pregnancy test ≤72 hours before the first dose of study intervention
  • Has provided an archival or newly-obtained tumor tissue sample adequate for Programmed Cell Death Ligand 1 (PD-L1) testing as determined by central laboratory testing
  • Has a life expectancy of >3 months
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 ≤10 days prior to the first dose of study intervention

Exclusion Criteria:

  • Has macroscopic residual cSCC after surgery and/or recurrence with active cSCC disease before randomization
  • Has any other histologic type of skin cancer other than invasive cSCC (eg, basal cell carcinoma) that has not been definitively treated with surgery or radiation; Bowen's disease; Merkel cell carcinoma; or melanoma
  • Has received prior therapy with an anti-programmed cell death receptor 1(PD-1), anti- PD-L1, or anti-programmed cell death receptor ligand 2 (PD-L2) agent or with an agent directed to another co-stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)
  • Has received prior systemic anticancer therapy including investigational agents for cSCC ≤4 weeks prior to randomization
  • Has not recovered from all radiation-related toxicities and has not had radiation pneumonitis
  • Has received a live vaccine ≤30 days prior to the first dose of study intervention
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device ≤4 weeks prior to the first dose of study intervention
  • Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
  • Has an active infection requiring systemic therapy
  • Has a known history of human immunodeficiency virus (HIV) infection
  • Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (HCV; defined as HCV RNA [qualitative] is detected) infection
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention
  • Has had an allogeneic tissue/solid organ transplant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03833167


Contacts
Layout table for location contacts
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

  Show 110 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme Corp.

Additional Information:
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03833167     History of Changes
Other Study ID Numbers: 3475-630
2018-001974-76 ( EudraCT Number )
MK-3475-630 ( Other Identifier: Merck Protocol Number )
KEYNOTE-630 ( Other Identifier: Merck )
First Posted: February 6, 2019    Key Record Dates
Last Update Posted: October 17, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme Corp.:
Programmed Cell Death-1 (PD-1)
Programmed Cell Death 1
PD1
Programmed Cell Death Ligand 1 (PD-L1)
Programmed Cell Death Ligand 2 (PD-L2)
PDL1
PDL2
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents