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Docetaxel

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Levoleucovorin

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Folinic Acid

Folate

Vitamin B9

LOTS as one cycle:

Leucovorin (30 mg) twice daily per oral, day 1 to 7; Oxaliplatin (85 mg per square meter) intravenously, day 1; Docetaxel (40 mg per square meter) intravenously, day 1; S-1 (35 mg per square meter) twice daily per oral, day 1 to 7

Pre-operative part:

Four cycles of LOTS every two weeks

Operative part:

Curative gastrectomy or gastroesophagectomy plus D2 lymphadenectomy

Post-operative part:

Four cycles of LOTS every two weeks

leucovorin, oxaliplatin, docetaxel, S-1

Clinical Trial Center, National Cheng-Kung University Hospital

Chih Chieh Yen, M.D.

I Shu Chen, M.D.

Li Yuan Bai, M.D., Ph.D.

Ying Jui Chao, M.D.

Ting Kai Liao, M.D.

Ping Jui Su, M.D.

I Ting Liu, M.D.

Kwang Yu Chang, M.D., Ph.D.

Chien Jui Huang, M.D.

Ming Huang Chen, M.D., Ph.D.

Chia Jui Yen, M.D., Ph.D.

Yan Shen Shan, M.D., Ph.D.

The aim of the trial is to investigate the clinical efficacy and toxicity of perioperative chemotherapy with leucovorin, oxaliplatin, docetaxel and S-1 (LOTS) in patients with locally advanced gastric or gastroesophageal junction adenocarcinoma who receive a curative surgery.

The study is an open-label, single-arm, single-country and multi-center phase II investigator-initiated trial. Patients with locally advanced gastric or gastroesophageal junction adenocarcinoma who enroll the trial will receive perioperative chemotherapy with LOTS (14 days as a cycle) 4 cycles every 2 weeks, followed by operation and another 4 cycles every 2 weeks post-operatively. The primary outcome is pathological response or curative resection rate. The secondary outcome includes recurrence-free survival, overall survival, disease control rate, protocol completion rate and adverse events.

Single intervention arm with trial treatment

Perioperative Leucovorin, Oxaliplatin, Docetaxel and S-1 (LOTS) For Locally Advanced Gastric or Gastroesophageal Junction Cancer

A Phase II Trial of Perioperative Chemotherapy With Leucovorin, Oxaliplatin, Docetaxel and S-1 (LOTS) For Patients With Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

All individual participant data which are processed with de-identification procedures and underlie results in a scientific publication

the tumor pathological response after pre-operative chemotherapy with LOTS plus curative surgery. The pathological response is defined by tumor evaluation of complete, partial or no response according to tumor regression grading (TRG)

the rate of margin-free (R0) resection in the absence of macro- or microscopic residual tumors remaining at the primary tumor bed

the time interval from the initiation of trial treatment to disease recurrence, progression or death at any causes

the time interval from the initiation of trial treatment to death at any causes

the rate of patients remaining in disease control (complete, partial response and stable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines version 1.1) lasting at least three months

the rate of patients completing the pre-specified protocol treatment

the rate of protocol treatment-emergent adverse events, as graded by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

TTY Biopharm

Kaohsiung Veterans General Hospital.

Taipei Veterans General Hospital, Taiwan

China Medical University Hospital

National Cheng-Kung University Hospital

Professor, Dean of College of Medicine, National Cheng Kung University

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

N-803 + pembrolizumab + PD-L1 t-haNK cells

400 mg administered as a 30 minute IV infusion on Day 1

N-803

15 ug/kg via subcutaneous injection on Day 1

pembrolizumab

Irradiated PD-L1 t-haNK cells at a dose of 2 x 10\^9 administered via IV infusion over 30 minutes on Days 1, 5, 8, 12, and 15

PD-L1 t-haNK cells

NCI Medical Oncology Referral Office

National Cancer Institute Referral Office

Jason M Redman, M.D.

Background:

Squamous cell carcinoma is a type of cancer that can cause tumors on the head and neck (HNSCC). Even with treatment, less than 50% of people with certain types of HNSCC survive for 5 years.

Objective:

To test a new drug treatment (N-803 and pembrolizumab, with or without PD-L1 t-haNK cells) in people with HNSCC. These drugs may help the immune system to fight cancer.

Eligibility:

People aged 18 years and older who have HNSCC that is not linked to human papillomavirus infection. They must not yet have received any treatment and be scheduled for surgery to remove the tumors.

Design:

Participants will be screened. They will have a physical exam with blood and urine tests. They will have imaging scans and a test of their heart function. They will have a biopsy: A sample of tissue will be removed from the tumor.

Pembrolizumab is given through a tube attached to a needle inserted into a vein in the arm (intravenous infusion). N-803 is injected under the skin of the abdomen. All participants will receive these 2 treatments on day 1. They will have follow-up visits on days 8 and 15.

Some participants will also receive PD-L1 t-haNK cells by intravenous infusion. These are cells that attack cancer cells. These participants will receive this treatment on days 1, 5, 8, 12, and 15.

All participants will have a clinic visit on day 21. They will have a second biopsy.

Follow-up visits will occur on days 49 and 105. Visits will continue by phone or email every 9 weeks for 2 years....

Background:

* Even in the potentially curative setting, human papillomavirus (HPV)-unrelated head and neck squamous cell carcinomas (HNSCC) are associated with dismal outcomes (compared to HPV-related) despite maximal surgical and adjuvant treatment (i.e., radiotherapy +/-chemotherapy).
* The window period between diagnosis and curative surgery provides a window of opportunity to administer therapies that may improve outcomes.
* Four published clinical trials suggest that neoadjuvant checkpoint blockade can improve recurrence-free survival (RFS) in resectable HNSCC (NCT02919683, NCT02488759, NCT02296684, NCT04247282). This includes NCI protocol 20C0024 (NCT04247282) where in addition to demonstrating improved 1-year RFS compared to historical values, our correlative studies provided insight into potential mechanisms of this benefit.
* N-803 (an IL-15 agonist) combined with anti-programmed cell death protein 1 (PD-1) therapies work toward maximization of T cell-mediated anti-tumor activity, a key component of anti-tumor immunity. However, expression of T cell inhibitory receptors and/or loss of antigen presentation and processing machinery, often driven by T cell activity s release of interferon-gamma renders some tumor cells invulnerable to T cell killing.
* Studies conducted by collaborators at the NCI have shown that programmed death-ligand (PD-L1) t-haNK can lyse such T-cell-resistant tumor cells. Additionally, in a murine model of oral cancer, the triplet of PD-L1 t-haNK combined with pembrolizumab and N-803 resulted in more tumor control than the doublet combinations of these agents.
* PD-L1 t-haNK cells is an allogenic, irradiated (no engraftment), off-the-shelf cell line currently being studied in combination with pembrolizumab and N-803 in advanced/metastatic HNSCC (NCI CCR protocol 000096, (NCT04847466)). As of November 2022, 10 participants have been treated and the regimen has been well tolerated.
* In addition to potentially improving outcomes, testing this triplet in the neoadjuvant setting with pre-and post-treatment tumor biopsies provides an opportunity to gain insight into the mechanisms of this regimen s anti-tumor activity.

Objective

-To determine the pathologic tumor response (pTR) rate (viable tumor in 50% or less of the surgically resected primary tumor bed) in Arm 1 and Arm 2.

Eligibility criteria

* Histologically or cytologically confirmed previously untreated intermediate/high risk, p16-negative (if oropharyngeal primary tumor), squamous cell carcinoma of the head and neck (T1-T4, N0-N3, M0 stage II, III or IV.
* Age \>= 18 years.
* Eastern Cooperative Oncology Group (ECOG) performance status \<= 1 and adequate organ function.

Design

* This is an open-label, single-site, non-randomized, phase II study to evaluate the efficacy of combined treatment of PD-L1 t-haNK cells, pembrolizumab, and N-803.
* The first 15 participants will be enrolled in Arm 1 and treated with pembrolizumab and N-803, the following participants will be enrolled in Arm 2 and treated with pembrolizumab, N-803, and PD-L1 t-haNK cells.
* All participants (Arm 1 and Arm 2) will receive treatment consisting of one intravenous (IV) infusion of pembrolizumab and one subcutaneous (SC) injection of N-803 on Day 1.
* Participants in Arm 2 will receive additional treatment with IV infusion of PD-L1 t-haNK cells on Days 1, 5, 8, 12, and 15.
* Participants will be monitored for 2 years.

Pembrolizumab + N-803 Alone or in Combination With PD-L1 t-haNK Cells for Resectable Head and Neck Squamous Cell Carcinoma

A Phase II Sequential Window of Opportunity Trial of Pembrolizumab + N-803 Alone or in Combination With PD-L1 t-haNK Cells for Resectable Head and Neck Squamous Cell Carcinoma

.All collected IPD will be shared. All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.

Digital pathology software assessment of H and E slides from the surgical specimen. The fraction of participants on each arm who experience a pathologic tumor response (pTR) will be reported along with a 95% confidence interval.

Any toxicities identified after the study treatment was administered. Safety will be evaluated by determining the frequency of adverse events among treated participants and reporting the results, by maximum grade of event and type of toxicity noted.

CT scans of chest and neck with contrast. Determined on each arm separately using a Kaplan-Meier curve. The one-year and two-year OS and RFS will be determined and reported on each arm along with a 95% confidence interval.

After treatment, contact the participant on days 49, 105 and every 9 weeks until death or 2 years after treatment initiation. Determined on each arm separately using a Kaplan-Meier curve. The one-year and two-year OS and RFS will be determined and reported on each arm along with a 95% confidence interval.

Record the date of diagnosis and date of definitive surgery.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Perioperative Leucovorin, Oxaliplatin, Docetaxel and S-1 (LOTS) For Locally Advanced Gastric or Gastroesophageal Junction Cancer	NCT04999332	Gastric Cancer Gastric Adenoca... Effects of Chem... Toxicity Due to...	leucovorin, oxa...	20 Years -	National Cheng-Kung University Hospital
Pembrolizumab + N-803 Alone or in Combination With PD-L1 t-haNK Cells for Resectable Head and Neck Squamous Cell Carcinoma	NCT06161545	Stage II Squamo... Stage III Squam... Stage IV Squamo...	N-803 pembrolizumab PD-L1 t-haNK ce...	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for triplet

Every month we try and update this database with for triplet cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for triplet

Every month we try and update this database with for triplet cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for triplet cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.