Neoplasms

All Conditions

Symptoms and General Pathology

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Adenocarcinoma

Syndrome

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Adenocarcinoma of the Appendix

Small Intestinal Adenocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Atezolizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Immunologic Factors

Participants receive cobimetinib PO QD on days 1-21 and atezolizumab IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cobimetinib

Kanwal P Raghav

This phase II trial studies how well cobimetinib and atezolizumab work in treating participants with rare tumors that have spread to other places in the body (advanced) or that does not respond to treatment (refractory). Cobimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cobimetinib and atezolizumab may work better in treating participants with advanced or refractory rare tumors.

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of cobimetinib plus atezolizumab (COTEZO) in cohorts of advanced rare tumors using objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.

SECONDARY OBJECTIVES:

I. To determine progression-free survival (PFS) on COTEZO in cohorts of advanced rare tumors per RECIST v1.1 and immune-related (ir)RECIST.

II. To determine overall survival (OS) on COTEZO in cohorts of advanced rare tumors.

III. To determine disease control rate (DCR) and duration of response (DOR) on COTEZO in cohorts of advanced rare tumors per RECIST v1.1 and irRECIST.

IV. To determine objective response rate (ORR) per immune-related RECIST criteria.

V. To determine safety profile and adverse events encountered by patients with advanced rare tumors treated with COTEZO.

VI. To collect and bank tumor tissue and peripheral blood for future correlative analyses from patients with advanced rare tumors treated with COTEZO.

OUTLINE:

Participants receive cobimetinib orally (PO) once daily (QD) on days 1-21 and atezolizumab intravenously (IV) over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants followed up every 3 months thereafter.

Cobimetinib and Atezolizumab in Treating Participants With Advanced or Refractory Rare Tumors

A Phase II, Open-Label, Single-Arm, Multi-Cohort, Proof-of-Principle Study to Investigate the Efficacy of Cobimetinib and Atezolizumab in Advanced Rare Tumors

ORR (partial response (PR) or complete response (CR) measured as per RECIST 1.1.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Recurrence

Panitumumab

Talimogene laherparepvec

Immunoglobulins, Intravenous

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)

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

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

Overall Study

Skin and Connective Tissue Diseases

Skin Neoplasms

Skin Diseases

Immunomodulating Agents

Cemiplimab

Participants have locally advanced, unresectable cutaneous squamous cell carcinoma/CSCC

Participants will undergo baseline imaging, followed by two doses of neoadjuvant cemiplimab at a dose of 350 mg intravenously over 30 minutes every 3 weeks (+/-3 days). Then, participants will receive concurrent cemiplimab 350 mg intravenously over 30 minutes every 3 weeks (+/-3 days) concurrently with RT to 70 Gy in 35 fractions over 7 weeks. Thereafter, participants will receive 38 weeks of cemiplimab 350 mg intravenously over 30 minutes every 3 weeks (+/-3 days) for a cumulative total of 12 months of cemiplimab.

Participants will receive radiotherapy to 70 Gy in 35 fractions over 7 weeks concurrently with cemiplimab

Radiotherapy

Christopher Barker, MD

Lara Dunn, MD

Ryan Lanning, MD, PhD

Evan Wuthrick, MD

Zachary Buchwald, MD, PhD

Shlomo Koyman, MD

Thomas Galloway, MD

Bhisham Chere, MD

Upendra Parvathaneni, MD

The purpose of the study is to see if the combination of radiation therapy and cemiplimab immunotherapy is an effective treatment for people with locally advanced, unresectable CSCC.

A Study of Radiation Therapy and Cemiplimab for People With Skin Cancer

A Phase II, Multicenter, Single-Arm Clinical Trial of Radiotherapy and CeMiPlimAb: Rwlc ImmunoTherapy for Locally Advanced, Unresectable Cutaneous Squamous Cell Carcinoma: RAMPART

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

The primary endpoint for this study is disease free survival at 18 months (week 78 +/- 3 weeks) after starting cemiplimab.

Memorial Sloan Kettering Cancer Center

Patients undergo SBRT on days 1, 3, 5, 7, and 9 of cycle 1. Beginning 1-2 days after SBRT, patients also receive atezolizumab IV on day 1. Treatment repeats every 3 weeks for 3 cycles in the absence of disease progression or unacceptable toxicity.

Stereotactic Body Radiation Therapy

Arya Amini

This phase I trial tests the safety and side effects radiotherapy in combination with atezolizumab in treating patients with cutaneous squamous cell cancer that has spread to nearby tissue or lymph nodes (locally advanced) and can be removed from surgery (resectable) or cannot be remove by surgery (unresectable). Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving radiotherapy in combination with atezolizumab may help improve outcomes for remission (cancer that is under control) than taking either treatment separately.

PRIMARY OBJECTIVE:

I. To determine the safety profile of combination of atezolizumab + radiation therapy (RT) in borderline resectable or unresectable cutaneous squamous cell carcinoma (cSCC).

SECONDARY OBJECTIVES:

I. Determine pathologic response after neoadjuvant atezolizumab + RT. II. Determine clinical response (via imaging and clinical exam) postoperatively (if surgically resectable) or at post-treatment biopsy (if not surgically resectable), and 3 months following the completion of surgery or RT (if not surgically resectable).

III. Define the toxicity profile associated with the treatment protocol. IV. Assess short-term quality-of-life associated with the treatment protocol.

EXPLORATORY OBJECTIVES:

I. To compare immune checkpoint molecule (e.g. PD1, PD-L1, TIM3, TIGIT, etc.) expression intensity within tumor cells and immune cells in the tumor microenvironment, as well as immune cell subset infiltration patterns including T cells before and after atezolizumab + stereotactic body radiation therapy (SBRT) by multiplex immunohistochemistry (or immunofluorescence).

II. To evaluate the impact of tumor molecular features on immune response and treatment outcome using next generation targeted deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) sequencing of pre-treatment tumor tissue.

III. To compare changes in circulating immune cell subsets in peripheral blood by RNA-based T-cell receptor (TCR)-sequencing and immunophenotyping by flow cytometry (or immunophenotyping by single-cell RNA sequencing), and correlate changes with response, clinical outcomes, and toxicity.

IV. To evaluate circulating tumor DNA (ctDNA) levels before start of treatment and immediately prior to surgery/repeat biopsy.

OUTLINE:

Patients undergo SBRT on days 1, 3, 5, 7, and 9 of cycle 1. Beginning 1-2 days after SBRT, patients also receive atezolizumab intravenously (IV) on day 1. Treatment repeats every 3 weeks for 3 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study, patients are followed up every 12 weeks for 24 months.

Radiotherapy in Combination With Atezolizumab in Locally Advanced Borderline Resectable or Unresectable Cutaneous SCC

Phase I Trial of Radiotherapy in Combination With Atezolizumab in Borderline Resectable and Unresectable Cutaneous Squamous Cell Carcinoma(cSCC)

Toxicity will be assessed by Common Terminology Criteria for Adverse Events version 5 criteria.

Will be calculated as the ratio of the number of patients who demonstrated a complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) divided by the number of patients evaluable for response.

Will be examined using the Kaplan-Meier method. Median OS and corresponding two-sided 95% confidence intervals will be computed.

Will be examined using the Kaplan-Meier method. Median PFS and corresponding two-sided 95% confidence intervals will be computed.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cobimetinib and Atezolizumab in Treating Participants With Advanced or Refractory Rare Tumors	NCT03108131	Skin Squamous C... Appendix Adenoc... Rare Lesion Locally Advance... Locally Advance... Metastatic Mali... Metastatic Skin... Metastatic Smal... Rare Neoplastic... Refractory Mali... Stage IV Small ... Unresectable Ma...	Atezolizumab Cobimetinib	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 Study of Radiation Therapy and Cemiplimab for People With Skin Cancer	NCT05574101	Cutaneous Squam... Skin Cancer Squamous Cell C... Locally Advance... Locally Advance... Locally Advance... Locally Advance...	Cemiplimab Radiotherapy	18 Years -	Memorial Sloan Kettering Cancer Center
Radiotherapy in Combination With Atezolizumab in Locally Advanced Borderline Resectable or Unresectable Cutaneous SCC	NCT05085496	Locally Advance... Resectable Skin... Unresectable Sk...	Atezolizumab Stereotactic Bo...	18 Years -	City of Hope Medical Center
A Study of Radiation Therapy and Cemiplimab for People With Skin Cancer	NCT05574101	Cutaneous Squam... Skin Cancer Squamous Cell C... Locally Advance... Locally Advance... Locally Advance... Locally Advance...	Cemiplimab Radiotherapy	18 Years -	Memorial Sloan Kettering Cancer Center
Radiotherapy in Combination With Atezolizumab in Locally Advanced Borderline Resectable or Unresectable Cutaneous SCC	NCT05085496	Locally Advance... Resectable Skin... Unresectable Sk...	Atezolizumab Stereotactic Bo...	18 Years -	City of Hope Medical Center
Radiotherapy in Combination With Atezolizumab in Locally Advanced Borderline Resectable or Unresectable Cutaneous SCC	NCT05085496	Locally Advance... Resectable Skin... Unresectable Sk...	Atezolizumab Stereotactic Bo...	18 Years -	City of Hope Medical Center

Spots Global Cancer Trial Database for locally advanced skin squamous cell carcinoma