Symptoms and General Pathology

All Conditions

Neoplasms

Recurrence

Carcinoma

Carcinoma, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Neoplasms, Squamous Cell

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Mitogens

Tyrosine Kinase Inhibitors

Erlotinib Hydrochloride

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Participants receive erlotinib PO QD in the absence of disease progression or unacceptable toxicity.

Erlotinib

Bonnie Glisson

This phase II trial studies how well erlotinib works in treating participants with skin squamous cell carcinoma that has spread to other places in the body or has come back. Drugs used in chemotherapy, such as erlotinib, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

PRIMARY OBJECTIVES:

I. To determine the overall response rate with erlotinib in patients with locoregionally recurrent or metastatic squamous cell carcinoma of the skin (CSCC) that is not amenable to curative treatment.

SECONDARY OBJECTIVES:

I. To determine duration of response and duration of stable disease. II. To determine progression-free and overall survival. III. To determine safety and tolerability of erlotinib.

EXPLORATORY OBJECTIVES:

I. To correlate baseline expression of estimated glomerular filtration rate (EGFR), expression of markers of EGFR activation (such as phosphorylated \[p\] EGFR and pAKT) and related cell-signaling pathways, and EGFR mutation status with response to erlotinib therapy.

II. To determine the effects of erlotinib on relevant biomarkers of the EGFR pathway in tumor tissue and in normal skin, and to correlate with response to therapy.

III. To determine if there is a correlation between the development of erlotinib-induced skin rash and response to therapy.

OUTLINE:

Participants receive erlotinib orally (PO) once daily (QD) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up every 3 months for up to 2 years.

Erlotinib in Treating Patients With Recurrent or Metastatic Skin Squamous Cell Carcinoma

Phase II Study of Erlotinib, An Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor, in the Treatment of Recurrent or Metastatic Squamous Cell Carcinoma of the Skin

Overall response rate defined as the percentage of patients who achieve an overall response of complete response or partial response in the total number of evaluable patients, assessed by Response Evaluation Criteria in Solid Tumors 1.1A Bayesian design based on predictive probability will be implemented.

The time from initial response during therapy to progression of disease evaluated using Kaplan-Meier estimation techniques.

The date of stable disease to the date of loss of stable disease or last follow-up.

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Time from date of treatment start until date of death due to any cause or last Follow-up.

Frequency of adverse events according to the NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0. Standard reporting guidelines followed for adverse events.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Bonnie Glisson, MD,Professor, Thoracic-Head & Neck Med Onc

Overall Response Rate

Duration of Response

Duration of Stable Disease

Progression-free Survival

Overall Survival

Dry eyes

Watery eyes

Constipation

Nausea/Vomitting

Oral Mucositis

Fatigue

Acneiform rash

Number of Participants With Safety and Tolerability of Erlotinib

Overall Study

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Panitumumab

Talimogene laherparepvec

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Immunologic Factors

Patients receive talimogene laherparepvec IM on day 1. Patients then receive talimogene laherparepvec IM and panitumumab IV over 30-90 minutes on day 22. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive up to 3 additional cycles of treatment per physician discretion.

Talimogene Laherparepvec

Adam C Berger, MD, FACS

This phase I trial studies the side effects and how well talimogene laherparepvec and panitumumab work in treating patients with squamous cell carcinoma of the skin that has spread to nearby tissues or lymph nodes (locally advanced) or other places in the body (metastatic). Talimogene laherparepvec is a type of vaccine made from a gene-modified virus that may help the body build an effective immune response to kill tumor cells. Immunotherapy with monoclonal antibodies, such as panitumumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving talimogene laherparepvec and panitumumab may work better in treating patients with squamous cell carcinoma of the skin compared to panitumumab alone.

PRIMARY OBJECTIVES:

I. To determine the safety of the combined treatment of talimogene laherparepvec and panitumumab.

II. To determine the preliminary efficacy of the combined treatment of talimogene laherparepvec and panitumumab, in comparison to single-agent panitumumab by historical control.

SECONDARY OBJECTIVES:

I. To assess the clinical efficacy of panitumumab in combination with intratumoral talimogene laherparepvec in terms of immune-related progression-free survival (irPFS) at 12 months, progression-free survival (PFS) hazard ratio, overall response rate (ORR), 1-year survival, overall survival (OS) and time to resectability.

II. To measure the pathologic complete response rate to panitumumab combined with talimogene laherparepvec.

III. Assess the response of injected and non-injected tumor deposits after panitumumab and talimogene laherparepvec.

IV. Assess the time to initial response. V. Assess the durable response rate.

VI. To analyze the following molecular correlates with response to therapy to confirm mechanism of action, and identify potential future targeted strategies and biomarkers of response:

VIa. Mutation load in tumor tissue by next generation sequencing. VIb. Deoxyribonucleic acid (DNA) mutation signature in tumor tissue pre- and post-therapy by next generation sequencing.

VIc. Messenger ribonucleic acid (mRNA) signature in tumor tissue pre-and post-therapy by Nanostring technology.

VId. Immune cell populations and immune profile in pre- and post-therapy tumor tissue and peripheral blood by flow cytometry and immunohistochemistry (IHC).

OUTLINE:

Patients receive talimogene laherparepvec intratumorally (IM) on day 1. Patients then receive talimogene laherparepvec IM and panitumumab intravenously (IV) over 30-90 minutes on day 22. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive up to 3 additional cycles of treatment per physician discretion.

After completion of study treatment, patients are followed up at 30 days and then every 2 months for 2 years.

Talimogene Laherparepvec and Panitumumab for the Treatment of Locally Advanced or Metastatic Squamous Cell Carcinoma of the Skin

A Phase 1 Study of Talimogene Laherparepvec and Panitumumab in Patients With Locally Advanced Squamous Cell Carcinoma of the Skin (SCCS)

Number of participants who experience adverse effects greater than or equal to a grade three as defined by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Grade 1-4, with 4 being the most severe.

Response will be evaluated by using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Changes in the largest diameter (unidimensional measurement)of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used for tumor measurements.

Best response on treatment was based on RECIST 1.1 criteria. Complete response (CR) is complete disappearance of all targeted lesions. Partial response (PR) is at least 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference baseline sum. LD Progressive disease (PD) is at least 20% increase in the sum of the longest diameter of the targeted lesions, taking as reference the smallest sum recorded in treatment PD for the evaluation of non-targeted lesions is the appearance of one or more new lesions and or progression of non-targeted lesions. Stable disease is defined as any condition not meet above criteria. The response rate of the drug will be assessed according to the decision rule based on Simons two-stage design.

Will be defined as the percent of participants with complete response or partial response maintained continuously for a minimum of six months. The response rate of the drug will be assessed according to the decision rule based on Simons two-stage design.

The response rate of the drug will be assessed according to the decision rule based on Simon?s two-stage design.

The estimate of PFS will be performed by the Kaplan-Meier product limit model.\>valuated by RECIST 1.1.

The estimate of OS will be performed by the Kaplan-Meier product limit model.

Next generation sequencing (NGS) is a massively parallel sequencing technology that offers ultra-high throughput, scalability, and speed. The technology is used to determine the order of nucleotides in entire genomes or targeted regions of DNA or RNA, and has the ability to detect variants at lower allele frequencies. With response to therapy and but the actual knowledge of the genetic basis of participants disease.

Will be analyzed by next generation sequencing with response to therapy.

Nanostring is an amplification-free technology that measures nucleic acid content by counting molecules directly. NanoString provides several pre-made gene expression panels that examine up to 770 genes at once and custom CodeSets for up to 800 targets. With response to therapy and descriptive statistics applied.

Will be analyzed by flow cytometry with response to therapy.

Cytometry, in its purest form, is the measurement of cell characteristics. Flow cytometry can identify the type of cells in a blood or bone marrow sample, including the types of cancer cells. It detects types of cancer cells based on either the presence or the absence of certain protein markers (antigens) on a cell's surface. This technique allows researchers to get highly specific information about individual cells. Flow cytometry will be used, with response to therapy and descriptive statistics applied.

Will be analyzed by flow cytometry, any suspended particle or cell from 0.2-150 micrometers in size, is suitable for analysis.

Will be analyzed by flow cytometry, any suspended particle or cell from 0.2-150 micrometers in size is suitable for analysis, with response to therapy.

Pathologic complete response (pCR) was defined as percent necrosis of the surgical specimen greater than or equal to 90% .Pathologic complete response (pCR) is a surrogate endpoint to demonstrate the study drug's efficacy.

A resectable tumor is one in which there is no technical barrier to surgical excision. Able to be removed by surgery.

Rutgers, The State University of New Jersey

Associate Director for Shared Resources, Chief of Melanoma and Soft Tissue Sarcoma Surgical Oncology

Participants receive Talimogene Laherparepvec IM on day one. Participants then receive Talimogene Laherparepvec IM and panitumumab IV over 30-90 minutes on day 22. Treatment repeats every two weeks for up to three cycles in the absence of disease progression or unacceptable toxicity. Participants may receive up to three additional cycles of treatment per physician discretion.

Panitumumab: Given IV

Talimogene Laherparepvec: Given IM

Treatment (Talimogene Laherparepvec, Panitumumab)

Dr. Adam Berger

Number of Participants With Treatment Related Adverse Events as Assessed by CTCAE v4.0

Response Rate to Panitumumab as Measured by Evaluation of the Criteria in Solid Tumors (RECIST) 1.1.

Best Overall Response Rate (ORR) of Participants From Start to Progression of Disease

Durable Response Rate Based on Simons Two-stage Design

Duration of Response Based on Simons Two-stage Design

Progression-free Survival (PFS) to Assess Participants Progressive Free-survival

Change in Overall Survival (OS) Measured by the Kaplan-Meier

Mutation Load in Tumor Tissue Measured by Next Generation Sequencing

Deoxyribonucleic Acid Mutation Signature in Tumor Tissue

Messenger Ribonucleic Acid Signature in Tumor Tissue Measured by Nanostring Technology

Immune Cell Populations in Tumor Tissue

Immune Cell Populations Peripheral Blood as Measured by Flow Cytometry

Expression of Cytokines in Tumor Tissue

Expression of Cytokines in Peripheral Blood

Pathologic Complete Response Rate

Time to Resectability

Skin and Connective Tissue Diseases

Skin Neoplasms

Skin Diseases

Cemiplimab

Patients receive cemiplimab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles (or up to 4 cycles for patients whose disease is unresectable after 3 cycles) in the absence of disease progression or unacceptable toxicity. Within 6 weeks of last dose of therapy, patients with potentially resectable tumors undergo surgical resection.

Resection

Charlean Ketchens, RN

Charlean Ketchens

Gino K. In, MD

Cristina de Leon

Jacob S. Thomas, MD

Kavita Shah

Sunandana Chandra, MD

Gino K In, MD

This phase II trial studies how well cemiplimab before surgery works in treating patients with skin cancer that is high-risk and has not spread to other parts of the body (localized), has come back locally (locally recurrent), or has spread regionally (regionally advanced), and can be removed by surgery (resectable). Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVE:

I. To assess the pathological partial response (PPR) rate in patients with potentially resectable cutaneous squamous cell carcinoma (CSCC) treated with neoadjuvant cemiplimab.

SECONDARY OBJECTIVES:

I. To estimate the pathological complete response rate (PCR). II. To estimate the Response Evaluation Criteria in Solid Tumors (RECIST) (version \[v\]1.1) 9 week objective response rate (ORR).

III. To estimate the RECIST (v1.1) 12 month progression free (PFS). IV. To assess the toxicity among patients with CSCC treated with neoadjuvant cemiplimab.

EXPLORATORY OBJECTIVES:

I. To evaluate tumor mutational burden (TMB) and correlate with response to PD-1 blockade therapy.

II. To evaluate PD-L1 expression on CSCC tumor cells and correlate with response to PD-1 blockade.

III. To evaluate CD8+ T cell infiltration into CSCC tumors and correlate with response to PD-1 blockade.

IV. To assess other adaptive immune resistance mechanisms in CSCC tumors.

OUTLINE:

Patients receive cemiplimab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles (or up to 4 cycles for patients whose disease is unresectable after 3 cycles) in the absence of disease progression or unacceptable toxicity. Within 6 weeks of last dose of therapy, patients with potentially resectable tumors undergo surgical resection.

After completion of study treatment, patients are followed up every 3 months for 24 months.

A PD-1 Checkpoint Inhibitor (Cemiplimab) for High-Risk Localized, Locally Recurrent, or Regionally Advanced Skin Cancer

Evaluating the PD-1 Checkpoint Inhibitor, Cemiplimab, as Neoadjuvant Therapy in High Risk Localized, Locally Recurrent, and Regionally Advanced Cutaneous Squamous Cell Carcinoma: A Phase II Pilot Study

Defined by presence of \< 50% malignant cells. Descriptive statistics will be used to summarize the measurements.

Descriptive statistics will be used to summarize the measurements.

Measured by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Descriptive statistics will be used to summarize the measurements.

Measured by RECIST v1.1. Descriptive statistics will be used to summarize the measurements.

All toxicities will be summarized and graded according to maximum grade by Common Terminology Criteria for Adverse Events v4. Descriptive statistics will be used to summarize the measurements.

University of Southern California

NEOADJUVANT PHASE: Prior to standard of care surgery, patients receive cemiplimab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

ADJUVANT PHASE: Within 2-6 weeks after standard of care radiation therapy (or surgery if no radiation therapy), patients receive cemiplimab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity.

Undergo standard of care radiation therapy

Radiation Therapy

Therapeutic Conventional Surgery

Michael Lowe, MD

Allyson R. Anderson

This phase I trial studies how well cemiplimab before and after surgery works in treating patients with high risk cutaneous squamous cell cancer. Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cemiplimab before surgery may improve risk of the cancer returning in patients with high risk cutaneous squamous cell cancer.

PRIMARY OBJECTIVE:

I. To establish the pathologic response rate of neoadjuvant cemiplimab in cutaneous squamous cell carcinoma (cSCC).

SECONDARY OBJECTIVES:

I. To document the local recurrence rate of high-risk cSCC treated with adjuvant cemiplimab.

II. To document the systemic recurrence rate of high-risk cSCC treated with adjuvant cemiplimab.

III. To document the 6-month, 12-month, 2-year overall survival (OS), recurrence-free survival (RFS) for patients with high risk cSCC.

TERTIARY/EXPLORATORY OBJECTIVE:

I. To evaluate the immune profile of fresh tumor tissue, blood in patients with cSCC treated with cemiplimab.

OUTLINE:

NEOADJUVANT PHASE: Prior to standard of care surgery, patients receive cemiplimab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

ADJUVANT PHASE: Within 2-6 weeks after completion of standard of care radiation therapy (or surgery if no radiation therapy), patients receive cemiplimab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks for 2 years, every 6 months for the next 3 years, and then annually for up to 10 years.

Cemiplimab Before and After Surgery for the Treatment of High Risk Cutaneous Squamous Cell Cancer

Pilot Study of Neoadjuvant/Adjuvant Cemiplimab for High Risk Cutaneous Squamous Cell Carcinoma

Results of the trial and not individual patient data will be shared. The study protocol, consent, and investigator's brochure will be available. The statistical plan is incorporated into the protocol, along with inclusion and exclusion criteria.

Pre- and post-surgery assessments of biomarkers extracted from tissue and blood samples will be summarized using frequencies and percentages for categorical variables, and mean, median, standard deviation, and range for numeric variables. Pre- versus (vs.) post-surgery values will be compared using paired t-tests or McNemar's tests, where appropriate. Biomarkers extracted from blood samples will also be collected at progression or completion of adjuvant therapy. In those cases, mixed models with a random intercept will be explored to assess the impact of time on change in biomarker status. Change in biomarker will be compared across response (yes/no) using two-sample t-tests or Mann Whitney U tests, where appropriate, and the and the impact of pre-surgery, post-surgery, and change in biomarker will be compared across survival endpoints using log-rank tests and univariate Cox proportional hazards models.

Defined as the number of complete and partial responses divided by the total number of patients, as assessed by pathology. Pathological complete response (pCR) (no viable tumor) or pathological partial response (pPR) (less than 50% viable tumor) as well as near pCR (less than 10% viable tumor) in the tumor bed will be documented by pathology from the resection specimen. Pathologic response rate will be summarized using frequency and percentage, and a 95% exact confidence interval will be reported using the Clopper-Pearson method.

Local recurrence-free survival will be estimated using the Kaplan-Meier method.

Systemic recurrence-free survival will be estimated using the Kaplan-Meier method.

OS will be estimated using the Kaplan-Meier method. 6-month, 12-month, and 24-month OS estimates will be reported along with 95% confidence intervals.

RFS will be estimated using the Kaplan-Meier method. 6-month, 12-month, and 24-month RFS estimates will be reported along with 95% confidence intervals.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Erlotinib in Treating Patients With Recurrent or Metastatic Skin Squamous Cell Carcinoma	NCT01198028	Metastatic Skin... Recurrent Skin ...	Erlotinib	18 Years -	M.D. Anderson Cancer Center
Erlotinib in Treating Patients With Recurrent or Metastatic Skin Squamous Cell Carcinoma	NCT01198028	Metastatic Skin... Recurrent Skin ...	Erlotinib	18 Years -	M.D. Anderson Cancer Center
Talimogene Laherparepvec and Panitumumab for the Treatment of Locally Advanced or Metastatic Squamous Cell Carcinoma of the Skin	NCT04163952	Locally Advance... Metastatic Skin... Recurrent Skin ...	Panitumumab Talimogene Lahe...	18 Years -	Rutgers, The State University of New Jersey
A PD-1 Checkpoint Inhibitor (Cemiplimab) for High-Risk Localized, Locally Recurrent, or Regionally Advanced Skin Cancer	NCT04315701	Recurrent Skin ... Resectable Skin... Stage I Skin Ca... Stage II Skin C... Stage III Skin ...	Cemiplimab Resection	18 Years -	University of Southern California
Cemiplimab Before and After Surgery for the Treatment of High Risk Cutaneous Squamous Cell Cancer	NCT04428671	Metastatic Skin... Recurrent Skin ...	Cemiplimab Radiation Thera... Therapeutic Con...	18 Years -	Emory University
A PD-1 Checkpoint Inhibitor (Cemiplimab) for High-Risk Localized, Locally Recurrent, or Regionally Advanced Skin Cancer	NCT04315701	Recurrent Skin ... Resectable Skin... Stage I Skin Ca... Stage II Skin C... Stage III Skin ...	Cemiplimab Resection	18 Years -	University of Southern California

Spots Global Cancer Trial Database for recurrent skin squamous cell carcinoma