- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04808999
Neoadjuvant Study of PD-1 Inhibitor Pembrolizumab in PD-1 Naive Cutaneous Squamous Cell Carcinoma (cSCC)
Phase II Neoadjuvant Study of PD-1 Inhibitor Pembrolizumab in PD-1 Naive Cutaneous Squamous Cell Carcinoma (cSCC)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Amy Rose, RN, BSN
- Phone Number: 412-647-8587
- Email: kennaj@upmc.edu
Study Locations
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, United States, 15232
- UPMC Hillman Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
1. Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of high-risk localized or locooregional cSCC as defined below may be enrolled in this study.
- NOTE: Patients are eligible for this trial either at initial presentation for cSCC with locally advanced and/or concurrent regional nodal metastasis; or at the time of recurrence with locally advanced and/or concurrent regional nodal metastasis assuming following criteria are met per the cSCC-specific AJCC UICC 8th edition staging classification
i. T2 and Nx and M0 (tumor >2 cm and ≤4 cm in greatest dimension) OR;
ii. T3 and Nx and M0 (tumor >4 cm or minor bone erosion or perineural invasion or deep invasion) OR;
- Deep invasion is defined as invasion beyond the subcutaneous fat or >6 mm (as measured from the granular layer of adjacent normal epidermis to the base of the tumor).
Perineural invasion is defined as tumor cells within the nerve sheath of a nerve lying deeper than the dermis or measuring 0.1 mm or larger in caliber, or presenting with clinical or radiographic involvement of named nerves without skull base invasion or transgression.
iii. T4 and Nx and M0 (tumor with gross cortical bone/marrow, skull base invasion and/or skull base foramen invasion if deemed surgically resectable) OR;
iv. Tx and N1-3 and M0 (if deemed surgically resectable) OR;
b. NOTE:
i. If T2, tumors must possess ≥2 NCCN/BWH clinical or pathologic risk factor(s) as stated below.
ii. NCCN/BWH clinical risk factors:
1. Tumors ≥20 mm on trunk or extremities (excluding pretibia, hands, feet, nail units, and ankles).
2. Tumors ≥10 mm on cheeks, forehead, scalp, neck, or pretibial areas.
iii. NCCN/BWH pathologic risk factors:
- Poorly defined borders.
- Recurrent tumors.
- Neurologic symptoms to suggest perineural invasion.
- High-risk histologic subtypes including: poorly differentiated tumor, acantholytic (adenoid), adenosquamous, desmoplastic, or metaplastic (carcinosarcomatous) subtypes (as stated in the pathology report or written documentation by Mohs surgeon).
Histopathologically documented perineural, lymphatic, or vascular involvement (as stated in the pathology report or written documentation by Mohs surgeon).
c. NOTE: Tumors of any size on the "mask areas" of the face [central face, eyelids, eyebrows, periorbital nose, lips (cutaneous and vermilion) are not eligible.
d. NOTE: Tumors of any size on genitalia, hands, and feet may be eligible at the discretion of the treating surgical oncologist.
e. NOTE: Patients with tumors that arise in the setting of chronic inflammation (Marjolin's ulcer) such as chronic wounds and/or scars are excluded.
f. NOTE: Determination of surgical resectability must be made before enrollment by the treating surgical oncologist (or ENT surgeon or equivalent).
2. Male participants: A male participant must agree to use a contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
3. Female participants:
A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
Not a woman of childbearing potential (WOCBP)
OR
A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
4. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
5. Have at least a single site of measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
6. Willing to undergo pre-treatment biopsies.
- Prior archival tumor tissue sample are not permitted.
Minimum tissue requirements: core (16G or 18G, 6 cores; preferred), punch or excisional biopsy of a tumor lesion that has not been previously irradiated.
7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
a. ECOG evaluation should be performed at Screening and repeated on Cycle 1 Day 1.
8. Have adequate organ function, per protocol criteria
Exclusion Criteria:
- Diagnosis of immunodeficiency, immunosuppression and/or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
- Prior chemotherapy, targeted small molecule therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
- Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 2-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
- A WOCBP who has a positive urine pregnancy test at Screening. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
Has received a live vaccine within 30 days prior to the first dose of study drug.
- Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine.
- Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior to the first dose of study drug.
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).
- Note: Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
Concurrent non-hematologic malignancy other than cSCC within 3 years of data of first planned dose of therapy except for tumors with a negligible risk of metastasis and/or death as defined below:
a. Adequately treated non-invasive malignancies including but not limited to melanoma in situ (MIS), BCC, CIS of cervix, or DCIS of breast may be enrolled.
b. Low-risk early stage prostate adenocarcinoma (T1-T2a N0 M0 and Gleason score ≤6 and PSA ≤10 ng/mL) for which the management plan is active surveillance, or prostate adenocarcinoma with biochemical-only recurrence with documented PSA doubling time of > 12 months for which the management plan is active surveillance may be enrolled.
c. Indolent hematologic malignancies for which the management plan is active surveillance including but not limited to CLL/indolent lymphoma may be enrolled.
i. Patients with high-risk hematologic malignancies (CML, ALL, AML, Hodgkin's or non- Hodgkin's lymphoma) are excluded even if the management plan is active surveillance.
Has known active CNS metastases and/or carcinomatous meningitis.
a. Note: Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during Screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
- 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) and/or known active Hepatitis C virus (defined as anti-HCV reactive) infection.
a. Patients with treated Hepatitis B/C with no evidence of active infection may be enrolled.
- Has a known history of active TB (Bacillus Tuberculosis).
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- 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 trial treatment.
- Has had an allogenic tissue/solid organ transplant.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Pembrolizumab
Neoadjuvant Phase: 200 mg IV infusion, every 3 weeks (Day 1 of each 3-week cycle, 2 cycles) Adjuvant Phase: Day 1 of each 3-week cycle, 15 cycles
|
200 mg IV infusion
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pathologic Complete Response (pCR)
Time Frame: At time of surgery
|
The proportion of patients with pathologic complete response (pCR) per Immune-Related Pathologic Response Criteria' (irPRC) criteria: 0% residual viable tumor (RVT)] remaining in post-therapy specimen (no signs of cancer) in tissue samples removed during surgery.
|
At time of surgery
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free Survival (PFS)
Time Frame: Up to 60 months
|
The median length of time from initiation of study drug(s) until disease relapse (disease progression) as defined by RECIST v1.1, or death.
Progressive Disease (PD): ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
The sum must also demonstrate an absolute increase of ≥5 mm.
The appearance ≥1 new lesion(s) is considered progression.
|
Up to 60 months
|
1-year PRS
Time Frame: Up to 12 months
|
The proportion of patients whose disease does not progress/relapse (as defined by RECIST v1.1), or cease to breath at 1 year after the initiation of treatment.
Progressive Disease (PD): ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
The sum must also demonstrate an absolute increase of ≥5 mm.
The appearance ≥1 new lesion(s) is considered progression.
|
Up to 12 months
|
6-month PFS
Time Frame: Up to 6 months
|
The proportion of patients whose disease does not progress/relapse (as defined by RECIST v1.1), or cease to breath at 6 months after the initiation of treatment.
Progressive Disease (PD): ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
The sum must also demonstrate an absolute increase of ≥5 mm.
The appearance ≥1 new lesion(s) is considered progression.
|
Up to 6 months
|
2-year PFS
Time Frame: Up to 24 months
|
The proportion of patients whose disease does not progress (as defined by RECIST v1.1), or cease to breath at 2 years after the initiation of treatment.
Progressive Disease (PD): ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
The sum must also demonstrate an absolute increase of ≥5 mm.
The appearance ≥1 new lesion(s) is considered progression.
|
Up to 24 months
|
3-year PFS
Time Frame: Up to 36 months
|
The proportion of patients whose disease does not progress/relapse (as defined by RECIST v1.1), or cease to breath at 3 years after the initiation of treatment.
Progressive Disease (PD): ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
The sum must also demonstrate an absolute increase of ≥5 mm.
The appearance ≥1 new lesion(s) is considered progression.
|
Up to 36 months
|
Overall Survival (OS)
Time Frame: Up to 84 months
|
The median length of time from initiation of study treatment that patients remain alive.
|
Up to 84 months
|
1-year OS
Time Frame: Up to 12 months
|
The proportion of patients alive at 1 year after the initiation of treatment.
|
Up to 12 months
|
2-year OS
Time Frame: Up to 24 months
|
The proportion of patients alive at 2 years after the initiation of treatment.
|
Up to 24 months
|
Pathologic Response
Time Frame: From start of treatment, up to 24 months
|
Number of patients with response per Immune-Related Pathologic Response Criteria (irPRC) criteria: major pathologic response (<0 to ≤10% RVT); partial pathologic response (<10 to ≤50% RVT).
|
From start of treatment, up to 24 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Diwaker Davar, MD, M.Sc, UPMC Hillman Cancer Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- HCC 20-300
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Squamous Cell Carcinoma
-
Sidney Kimmel Cancer Center at Thomas Jefferson...Bristol-Myers SquibbCompletedStage IVA Oral Cavity Squamous Cell Carcinoma | Stage IV Hypopharyngeal Squamous Cell Carcinoma | Stage IVA Laryngeal Squamous Cell Carcinoma | Stage IVA Oropharyngeal Squamous Cell Carcinoma | Stage IVB Laryngeal Squamous Cell Carcinoma | Stage IVB Oropharyngeal Squamous Cell Carcinoma | Stage... and other conditionsUnited States
-
National Cancer Institute (NCI)TerminatedRecurrent Hypopharyngeal Squamous Cell Carcinoma | Recurrent Laryngeal Squamous Cell Carcinoma | Recurrent Oral Cavity Squamous Cell Carcinoma | Recurrent Oropharyngeal Squamous Cell Carcinoma | Stage IVA Oral Cavity Squamous Cell Carcinoma | Stage IVA Laryngeal Squamous Cell Carcinoma | Stage... and other conditionsCanada, United States
-
Emory UniversitySynta Pharmaceuticals Corp.TerminatedStage IVA Oral Cavity Squamous Cell Carcinoma | Stage IVA Laryngeal Squamous Cell Carcinoma | Stage IVA Oropharyngeal Squamous Cell Carcinoma | Stage I Hypopharyngeal Squamous Cell Carcinoma | Stage I Laryngeal Squamous Cell Carcinoma | Stage I Oropharyngeal Squamous Cell Carcinoma | Stage II... and other conditionsUnited States
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)TerminatedRecurrent Hypopharyngeal Squamous Cell Carcinoma | Recurrent Laryngeal Squamous Cell Carcinoma | Recurrent Oral Cavity Squamous Cell Carcinoma | Recurrent Oropharyngeal Squamous Cell Carcinoma | Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma | Stage IVA Oral Cavity Squamous Cell... and other conditionsUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)CompletedRecurrent Head and Neck Squamous Cell Carcinoma | Recurrent Hypopharyngeal Squamous Cell Carcinoma | Recurrent Laryngeal Squamous Cell Carcinoma | Caregiver | Salivary Gland Squamous Cell Carcinoma | Malignant Head and Neck Neoplasm | Recurrent Lip and Oral Cavity Squamous Cell Carcinoma | Stage... and other conditionsUnited States
-
NRG OncologyNational Cancer Institute (NCI)RecruitingAdvanced Head and Neck Squamous Cell Carcinoma | Squamous Cell Carcinoma of Unknown Primary | Advanced Hypopharyngeal Squamous Cell Carcinoma | Advanced Laryngeal Squamous Cell Carcinoma | Advanced Oropharyngeal Squamous Cell CarcinomaUnited States, Canada
-
City of Hope Medical CenterNational Cancer Institute (NCI); Genentech, Inc.RecruitingLocally Advanced Skin Squamous Cell Carcinoma | Unresectable Skin Squamous Cell Carcinoma | Resectable Skin Squamous Cell CarcinomaUnited States
-
Baptist Health South FloridaRegeneron PharmaceuticalsWithdrawnSquamous Cell Carcinoma | Cutaneous Squamous Cell Carcinoma | Advanced Squamous Cell CarcinomaUnited States
-
H. Lee Moffitt Cancer Center and Research InstituteAstraZeneca; Brooklyn ImmunoTherapeutics, LLCActive, not recruitingSquamous Cell Carcinoma of the Head and Neck | Oropharynx Squamous Cell Carcinoma | Squamous Cell Carcinoma | Oral Cavity Squamous Cell Carcinoma | Metastatic Squamous Cell Carcinoma | Hypopharynx Squamous Cell Carcinoma | Paranasal Sinus Squamous Cell Carcinoma | Larynx Squamous Cell CarcinomaUnited States
-
Hyunseok Kang, MDNeoImmuneTechRecruitingRecurrent Head and Neck Squamous Cell Carcinoma | Recurrent Hypopharyngeal Squamous Cell Carcinoma | Recurrent Laryngeal Squamous Cell Carcinoma | Recurrent Oral Cavity Squamous Cell Carcinoma | Recurrent Oropharyngeal Squamous Cell Carcinoma | Resectable Oropharyngeal Squamous Cell CarcinomaUnited States
Clinical Trials on Pembrolizumab Injection
-
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.Recruiting
-
University of UtahMerck Sharp & Dohme LLCTerminatedNeuroendocrine TumorsUnited States
-
Tianjin Medical University Cancer Institute and...RecruitingESCC | Adjuvant Treatment | Lymph Node Positive | PembrolizumabChina
-
Hunan Province Tumor HospitalCompletedUncommon Pathological Types of Lung CancerChina
-
CHA UniversityMerck Sharp & Dohme LLCNot yet recruitingGestational Trophoblastic NeoplasiaKorea, Republic of
-
Hefei TG ImmunoPharma Co., Ltd.RecruitingMelanoma | Colorectal Cancer | Ovarian Cancer | Triple Negative Breast CancerUnited States
-
University Medical Center GroningenCompleted
-
Summit TherapeuticsRecruitingNon-Small Cell Lung CancerUnited States, Canada
-
Binhui Biopharmaceutical Co., Ltd.Recruiting
-
Martin-Luther-Universität Halle-WittenbergUltimovacs ASA; Apotheke der Universitätsmedizin der Johannes Gutenberg-Universität... and other collaboratorsRecruitingHead and Neck Squamous Cell CarcinomaGermany