Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Carboplatin

Apatinib

Albumin-Bound Paclitaxel

Cisplatin

Protein Kinase Inhibitors

Enzyme Inhibitors

1. Neoadjuvant therapy:

   Apatinib:apatinib one course will last 21 days.Oral administration at a dose of 250 mg, qd; Abraxane:abraxane one course will last 21 days.Intravenously guttae at a dose of 260 mg/m2,d1; Cis-platinum or Carboplatin:cis-platinum or carboplatin one course will last 21 days.cis-platinum introperitoneal injection at a dose of 75-100 mg/m2,d1;carboplatin intravenous injection at a dose of AUC=5-6,d1.

   Neoadjuvant therapy is 3-4 cycles.After Neoadjuvant therapy will received interval cytoreductive surgery.
2. Adjuvant therapy:

   After interval cytoreductive surgery,patients will received adjuvant therapy same as neoadjuvant therapy.

   Adjuvant therapy is 3 cycles
3. maintenance treatment: After above treatment finished,patients will received aptinib for 2 years.

1.Adjuvant therapy:

After primary cytoreductive surgery,patients will received adjuvant therapy:

Apatinib:apatinib one course will last 21 days.Oral administration at a dose of 250 mg, qd; Abraxane:abraxane one course will last 21 days.Intravenously guttae at a dose of 260 mg/m2,d1; Cis-platinum or Carboplatin:cis-platinum or carboplatin one course will last 21 days.cis-platinum introperitoneal injection at a dose of 75-100 mg/m2,d1;carboplatin intravenous injection at a dose of AUC=5-6,d1.

Adjuvant therapy is 3 cycles 3.maintenance treatment: After above treatment finished,patients will received aptinib for 2 years.

apatinib one course will last 21 days.Oral administration at a dose of 250 mg, qd

Apatinib Mesylate

abraxane one course will last 21 days.Intravenously guttae at a dose of 260 mg/m2,d1

Abraxane

cis-platinum one course will last 21 days.cis-platinum introperitoneal injection at a dose of 75-100 mg/m2,d1

Cis Platinum

carboplatin one course will last 21 days.carboplatin intravenous injection at a dose of AUC=5-6,d1

Li Xiao, Doctor

Shuntian Cai

This monocentric, prospective, observational study will evaluate the safety and efficacy of apatinib in combination with albumin binds paclitaxel and carboplatin or cisplatinum as first-line treatment for stage II-IV epithelial ovarian cancer followed by apatinib maintenance therapy in routine clinical practice. Eligible patients will be followed for approximately 20 months.

Apatinib Combined With Abraxane and Carboplatin or Cisplatinum as First-line Treatment for Epithelial Ovarian Cancer

Apatinib Mesylate Combined With Albumin Binds Paclitaxel and Carboplatin or Cisplatinum as First-line Treatment for Stage II-IV Epithelial Ovarian Cancer Followed by Apatinib Maintenance Therapy:a Single-arm,Exploratory Clinical Study

defined as the proportion of patients with no gross tumor tissue residual after interval cytoreductive surgery

defined as time from first administration of first-line therapy to documented disease progression

Zhongshan Hospital Xiamen University

Symptoms and General Pathology

Respiratory Tract (Lung and Bronchial) Diseases

Death

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Micronutrients

Hematinics

Vitamins

Pembrolizumab

Pemetrexed

Immunomodulating Agents

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

Combination of CDDP at 75 mg/m2 (day 1) or CBDCA at Area Under the Curve=6 (AUC=6) (day 1) + PEM at 500 mg/m2 (day 1) will be administered to patients with non-squamous cell carcinoma at 3-week intervals. To those with squamous cell carcinoma, CBDCA at AUC=6 (day 1) + nab-PTX at 100 mg/m2 (days 1, 8, and 15) will be administered at 3-week intervals. If there is no progression after the 4th course of induction therapy, it will be switched to maintenance therapy. For maintenance therapy, the combination of PEM at 500 mg/m2 (day 1) + Pembrolizumab at 200 mg (day 1) will be administered to patients with non-squamous cell carcinoma at 3-week intervals. To those with squamous cell carcinoma, Pembrolizumab at 200 mg (day 1) will be administered at 3-week intervals until disease progression or intolerable toxicity. Pembrolizumab administration should be continued for 2 years involving induction and maintenance therapies or until the 35th course.

Pembrolizumab at 200 mg (day 1) will be administered to patients with non-squamous cell carcinoma at 3-week intervals. To those with squamous cell carcinoma, Pembrolizumab at 200 mg (day 1) will be administered at 3-week intervals until disease progression or intolerable toxicity. Pembrolizumab administration should be continued for 2 years involving induction and maintenance therapies or until the 35th course.

In patients with non-squamous histology, cisplatin (75 mg/m2) will be administered every 3 weeks until 4 cycles with pemetrexed and pembrolizumab.

In cisplatin-intolerable patients, carboplatin (AUC=6) will be administered every 3 weeks until 4 cycles with pemetrexed and pembrolizumab.

In patients with non-squamous histology, pemetrexed (500 mg/m2) will be administered every 3 weeks until progression or 2 years after initiation (35 cycles) with pembrolizumab.

In patients with squamous histology, nab-paclitaxel (100 mg/m2, day 1, 8, 15, tri-weekly) will be administered until 4 cycles with pembrolizumab.

nab paclitaxel

AKITO HATA, MD

Keisuke Tanigawa

Akito Hata

This is a phase II, multicenter, single-arm, non-blind study. To 21 patients with PD-L1 ≥50% locally advanced non-small cell lung cancer, the combination of Pembrolizumab and platinum-doublets will be intravenously administered without radiotherapy to evaluate the efficacy and safety of combination therapy with Pembrolizumab and platinum-doublets.

Trial procedure:

As induction therapy, ≤4 courses of combination therapy with Pembrolizumab at 200 mg (day 1) and a platinum preparation will be performed at 3-week intervals until disease exacerbation or intolerable toxicity appearance. Concerning combination therapy with a platinum preparation, the combination of cisplatin (CDDP) at 75 mg/m2 (day 1) or carboplatin (CBDCA) at Area Under the Curve=6 (AUC=6) (day 1) + pemetrexed (PEM) at 500 mg/m2 (day 1) will be administered to patients with non-squamous cell carcinoma at 3-week intervals. To those with squamous cell carcinoma, carboplatin (CBDCA) at AUC=6 (day 1) + nanoparticle albumin-bound paclitaxel (nab-PTX) at 100 mg/m2 (days 1, 8, and 15) will be administered at 3-week intervals. If there is no exacerbation after the 4th course of induction therapy, it will be switched to maintenance therapy. For maintenance therapy, the combination of PEM at 500 mg/m2 (day 1) + Pembrolizumab at 200 mg (day 1) will be administered to patients with non-squamous cell carcinoma at 3-week intervals. To those with squamous cell carcinoma, Pembrolizumab at 200 mg (day 1) will be administered at 3-week intervals until disease exacerbation or intolerable toxicity appearance. Pembrolizumab administration should be continued for 2 years involving induction and maintenance therapies or until the 35th course.

In each patient, diagnostic imaging will be performed every 6 weeks (42 ± 7 days)(every 9 weeks after Week 18, every 12 weeks after Week 45) to evaluate tumor-reducing effects. Using images, the response rate (RR) and progression-free survival (PFS) will be evaluated based on the "Guidelines for evaluating the treatment response of solid cancer (RECIST 1.1)". It is possible to continue treatment until PD evaluated by the attending physician based on the RECIST 1.1, intolerable toxicity appearance, the appearance of concomitant diseases affecting the continuation of treatment, discontinuation based on the study investigator's evaluation, withdrawal, pregnancy, incompliance with investigational-drug administration or procedures described in the protocol, appearance of management-related reasons, or completion of Pembrolizumab administration for 2 years involving induction and maintenance therapies or the 35th course. Even after PD is definitively diagnosed by the study investigator based on the RECIST 1.1, it is possible to continue treatment if the patient's condition is stable and if treatment is considered to be advantageous for the patient by the study investigator. During the trial period, adverse events should be examined,and severity grading should be performed according to the CTCAE（NCI Common Terminology Criteria for Adverse Events）version 5.0.

In cases without any response at first radiographic evaluation (6 weeks), local salvage therapy using radiotherapy is recommended by a discretion of doctors in charge. At that timing, such cases are treated as a censored case.

After enrollment of 10 cases, the trial will be early terminated by confirmed PD according RECIST at their initial radiographic evaluation (6 weeks) more than 3 cases.

Background:

Lung cancer accounts for 13% of all cancer patients. In 2012, 1,800,000 persons were newly diagnosed with lung cancer. Internationally, the number of patients who died of lung cancer in 2012 reached 1,600,000. Lung cancer is the most frequent cause of cancer-related death in males and the second most frequent cause of cancer-related death in females. Non-small cell lung cancer accounts for approximately 85% of all lung cancer lesions.

Concerning the treatment of non-small cell lung cancer, tumorectomy is performed in a stage in which radical resection is possible, and cure may be achieved at a relatively high probability. When radical resection is impossible, therapeutic strategies differ between patients with locally advanced cancer and those with remote metastasis. Standard treatment for stage III (locally advanced stage in which radical resection is impossible) non-small cell lung cancer is chemoradiotherapy (CRT). In some patients, radical cure may be achieved, but severe irreversible toxicities, such as treatment-associated death, pneumonia, and esophageal stenosis, may appear. In two phase III clinical studies regarding CRT for stage III lung cancer in which radical resection is impossible in Japan (WJTOG0105 and Osaka Lung Cancer Study Group 0007 studies), treatment-associated death and grade ≥3 pneumonia were observed in 3/4% and 2/10%, respectively. A recent phase II comparative clinical study in Japan (WJOG5008L study) compared CDDP + S-1 therapy with CDDP + vinorelbine therapy, and indicated that the treatment-associated mortality rates and incidences of grade ≥3 pneumonia were7.4/9.3% and 9.3/7.4%, respectively.

The rate at which radical cure was achieved by CRT was estimated to be approximately 20% based on the results of previous phase III clinical studies. In these studies, the PFS curve after CRT reached a plateau after 2 years. Briefly, if there is no relapse \>2 years after treatment, the possibility of relapse-free survival may be high. This suggests that the 2-year PFS rate, which is also adopted as a primary endpoint in this study, is a surrogate marker of overall survival (OS).

Recently, the results of CRT in stage III patients in whom radical resection is impossible have not markedly improved, but it was demonstrated that additional immunotherapy after CRT prolonged the prognosis. A phase III comparative clinical study published in 2017 (PACIFIC study) indicated that the additional administration of a PD-L1 antibody, Durvalumab, to patients after CRT in stage III, in which radical resection is impossible, for 1 year prolonged the PFS (median: 16.8 vs. 5.6 months, respectively; HR 0.52; p\<0.0001) and OS (median: not reached vs. 28.7 months, respectively; HR 0.68; p=0.0025) in comparison with a placebo. Based on the results of the study, 1-year Durvalumab administration following CRT was established as standard treatment for stage III cancer, which is impossible to treat by radical resection.

However, in the above study, randomization was performed after CRT, and the subjects did not include those with PD during CRT, those with grade ≥2 pneumonia, those with a reduction in the performance status (PS), those in whom CRT could not be completed, or those in whom Durvalumab could not be introduced within 42 days after CRT; Durvalumab should be additionally administered to patients who completed CRT, but it is difficult to notice treatment options before CRT. Furthermore, the results of the PACIFIC study may have been obtained, excluding these patients with poor prognoses.

In patients with PD-L1 ≥50% stage IV non-small cell lung cancer, the marked therapeutic effects of monotherapy with Pembrolizumab have been reported. In a phase III comparative study (Keynote-024), monotherapy with Pembrolizumab significantly prolonged the PFS (median: 10.7 vs. 6.7 months, respectively; HR 0.50; p\<0.001) and OS (median: non-reached vs. non-reached, respectively; HR 0.60; p=0.005) in comparison with combination therapy with a platinum preparation, as primary treatment, in patients with PD-L1 ≥50% stage IV non-small cell lung cancer. Based on the results of the study, monotherapy with Pembrolizumab was established as primary standard treatment for PD-L1 ≥50% stage IV non-small cell lung cancer. In addition, a strategy to combine immunotherapy with chemotherapy was examined. A phase II comparative study involving patients with stage IV non-squamous, non-small cell lung cancer (Keynote-021 cohort G) showed that CBDCA + PEM + Pembrolizumab therapy prolonged the PFS (median: 19.0 vs. 8.9 months, respectively; HR 0.54; p=0.0067) and OS (median: non-reached vs. 20.9 months, respectively; HR 0.59; p=0.03) in comparison with CBDCA + PEM therapy. Interestingly, a population in which a plateau was reached after ≥24 months accounted for approximately 45% regardless of PD-L1. Furthermore, 16 of 20 PD-L1 ≥50% patients responded to treatment, with a response rate of 80%. Grades 3-5 adverse events occurred in 39.0% of the patients. There was a treatment-associated death (1.7%). To confirm the data, a phase III comparative study (Keynote-189) was conducted, supporting the efficacy of CBDCA + PEM + Pembrolizumab therapy. In the study, the response rate (61.4 vs. 22.9%, respectively), PFS (HR 0.36), and OS (HR 0.42) were significantly higher/longer in the 3-drug combination group (involving immunotherapy) among PD-L1 ≥50% patients. As the observation period was insufficient, it is difficult to evaluate the 2-year PFS and OS rates in the PD-L1 ≥50% patients, but the PFS and OS rates at 18 months were estimated to be approximately 40 and 70%, respectively, based on the survival curves. Concerning adverse events, the incidence of grade ≥3 toxicities and treatment-associated mortality rate in the 3-drug combination group were 67.2 and 6.7%, respectively, being slightly high. However, in the placebo group, the percentages were 65.8 and 5.9%, respectively; there were no differences. Furthermore, a phase III randomized controlled study of initial treatment for stage IV squamous cell carcinoma of the lung (Keynote-407) demonstrated the additive effects of pembrolizumab on combination therapy with a platinum preparation (CBDCA + nab-PTX). This therapy improved the response rate (58.4 vs. 38.0%, respectively), PFS (median: 6.4 vs. 4.8 months, respectively; HR 0.56; p\<0.001), and OS (median: 15.9 vs. 11.3 months, respectively; HR 0.64; p=0.008). As the observation period was insufficient, it is difficult to evaluate the 2-year PFS and OS rates. However, the PFS and OS rates at 15 months were estimated to be approximately 30 and 50%, respectively, based on the survival curves. The hazard ratios (HRs) of PFS and OS in PD-L1 ≥50% patients were 0.37 and 0.64, respectively. Furthermore, there was no difference in the incidence of serious adverse events (grade ≥3) (69.8 vs. 68.2%, respectively). These data suggest the potent therapeutic effects of chemotherapy + Pembrolizumab in both PD-L1 ≥50% non-squamous and squamous cell carcinoma patients.

With respect to the effects of immunotherapy in an earlier stage, the efficacy of nivolumab as stage II/III preoperative therapy was reported. According to this report, nivolumab administered twice before surgery led to a major pathologic response (MPR rate: the rate of viable cells, \<10%) in 9 (43%) of 21 patients. A higher MPR rate may be achieved by preoperative chemotherapy + immunotherapy. According to a report from the American Society of Clinical Oncology in 2018, the MPR rate after CBDCA + nab-PTX + Atezolizumab therapy (n=14), as stage II/III preoperative treatment, was 50%. In addition, at a meeting held by the World Conference on Lung Cancer in 2018, it was reported that pathological complete remission was achieved in 18 (60%) of 30 surgically treated patients after CBDCA + PTX + nivolumab therapy, and that an MPR was achieved in 6 (20%); the MPR rate was 80%. These data also suggest that immunotherapy is more effective in an earlier stage, and that the combination of chemotherapy and immunotherapy is much more effective. Considering that a durable response is achieved in most patients with complete or partial remission among stage IV patients, a durable response may be achieved at a high probability in stage III patients with an MPR after chemotherapy + immunotherapy. Furthermore, a study indicated that, among stage IV patients, PD-1 antibody therapy was more effective in those with a smaller tumor volume. In stage III patients, there is no remote metastasis, and the tumor volume may be smaller than in stage IV patients. Therefore, considering a high MPR rate after stage II/III preoperative therapy and a more favorable patient status with a small tumor volume and a small number of metastatic organs in stage III patients, chemotherapy + immunotherapy may be more effective than chemotherapy + Pembrolizumab in stage IV patients.

Based on the above background, we hypothesized that Pembrolizumab + chemotherapy might exhibit sufficient therapeutic effects similar to those of CRT in the absence of radiotherapy if PD-L1 is ≥50% in patients with non-resectable stage III non-small cell lung cancer. Furthermore, the toxicity of CRT can be avoided, and there may be a marked improvement in tolerability. Therefore, we designed a phase II, multicenter, cooperative, single-group, physician-guided trial of combination chemotherapy with Pembrolizumab and a platinum preparation in the absence of radiotherapy involving PD-L1 ≥50% stage III locally advanced non-small cell lung cancer.

Pembrolizumab + Platinum Doublets Without Radiation for Programmed Death-ligand 1 (PD-L1) ≥50% Locally Advanced NSCLC

Pembrolizumab + Platinum Doublets Without Radiation for Patients With PD-L1 ≥50% Locally Advanced Non-small Cell Lung Cancer: a Multicenter Prospective Single Arm Phase II Study

Differences of Response rate in percent according to PD-L1 Total Proportion Score in percent

Differences of Progression-free survival in months according to PD-L1 Total Proportion Score in percent

Differences of Overall survival in months according to PD-L1 Total Proportion Score in percent

Number of non-progression cases/all enrolled cases at 2 years

Analysis of grade and incidence of adverse events

Merck Sharp & Dohme LLC

Kobe Minimally Invasive Cancer Center

Akito Hata, Director of Division of Thoracic Oncology

Digestive System Diseases

Carcinoma, Squamous Cell

Esophageal Squamous Cell Carcinoma

Neoplasms, Squamous Cell

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Fluorouracil

Tislelizumab

In the single experimental arm, patients with locally nonresectable disease were subjected to receive neoadjuvant tislelizumab (200mg) plus chemotherapy (FP regimen) for conversion therapy. If conversion therapy succeeds, patients would proceed to surgery and adjuvant therapy. Otherwise, if patients were still not resectable after the conversion therapy, they will be treated by tislelizumab plus chemotherapy with or without palliative radiotherapy .

The 1st to 3rd doses were administered concurrently with FP regimen chemotherapy, 200 mg Tislelizumab each, on D1, D22 and D43 by intravenous infusion. In patients with successful conversion, one dose of 200 mg was administered 21 days after surgery in concurrent with the 4th to 6th cycles of 5-Fu, then 6 cycles of 200 mg Tislelizumab as adjuvant therapy; in patients with failed conversion, chemotherapy combined with tislelizumab were administered, with or without radiation therapy.

A FP regimen with 5-Fu 850mg/m\^2 d1-4 + cis-platinum 850mg/m\^2 d1-4 was used, on D1, D22 and D43 infused intravenously. 3 cycles of 5-Fu 850mg/m\^2 d1-4 adjuvant chemotherapy were started at 21 days after surgery in patients with a successful conversion. In patients with failed conversion, chemotherapy combined with tislelizumab were administered, with or without radiation therapy.

5-FU

A FP regimen with 5-Fu 850mg/m\^2 d1-4 + cis-platinum 850mg/m\^2 d1-4 was used, on D1, D22 and D43 infused intravenously. In patients with failed conversion, chemotherapy combined with tislelizumab were administered, with or without radiation therapy.

cis Platinum

Tongpeng Xu, PhD

This is a single-arm，open-label study to evaluate the efficacy and safety of tislelizumab plus chemotherapy for conversion therapy of patients with locally nonresectable ESCC.

Tislelizumab in Combination With Chemotherapy for Conversion Therapy of Locally Nonresectable ESCC

The Safety and Efficacy of Tislelizumab in Combination With Chemotherapy for Conversion Therapy of Locally Nonresectable ESCC，A Single-arm Study

Translational treatment-related AEs resulted in rates of surgery that were more than 30 days late or inoperable than originally planned

The proportion of patients whose primary tumor cell residual was less than 10% in the total number of patients enrolled after transformation therapy

Pathological complete response refers to that no tumor component or a small amount of carcinoma in situ component can be found on the horizontal line of pathological section after systemic treatment and surgical resection of the lesion.

The proportion of patients who completed R0 resection through 3 cycles of immunotherapy combined with chemotherapy in the total enrolled population.R0 finger resection margin under microscope was negative.

The time from randomization to disease recurrence or death due to disease progression

The First Affiliated Hospital with Nanjing Medical University

Docetaxel

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Induction chemotherapy with docetaxel 75mg/m2 on day 1, cisplatin 75mg/m2 on day 1, 5-FU 750mg from day 1 to day 5, given every 3 weeks for 3 cycles and tazemetostat 800mg twice daily orally for 3 cycles, followed by radical surgery or radical chemoradiation, and maintenance tazemetostat 800mg twice daily orally for 6 months

Docetaxel 75mg/m2 intravenous infusion on day 1 every 3 weeks for 3 cycles as induction therapy

Cisplatin 75mg/m2 intravenous infusion on day 1 every 3 weeks for 3 cycles as induction therapy

5-FU 750mg/m2 intravenous infusion from day 1 to day 5 every 3 weeks for 3 cycles as induction therapy

Tazemetostat 800mg twice per day orally in continuously for 3 cycles as induction therapy and maintenance therapy

Tazemetostat

Surgery

Chemoradiation as either radical treatment or post-operative treatment after surgery

Chemoradiation

Victor Ho Fun Lee, MD

Mike Law, BSc

SMARCB1-deficient sinonasal carcinoma is very locally advanced malignancy at diagnosis which often precluded upfront radical resection. The investigators are now proposing a phase II single-arm study on tazemetostat in combination with docetaxel, cisplatin and 5-FU (known as TPF regimen) as preoperative therapy for locally advanced non-metastatic SMARCB1 (INI-1)-deficient sinonasal carcinoma, followed by radical resection and/or post-operative radiation therapy (with or without concurrent chemotherapy), and tazemetostat for another 6 months. It is hypothesized that addition of tazemetostat will improve objective response rate, resectability rate, orbit preservation rate after surgery, and hopefully survival outcomes with manageable safety profiles.

SMARCB1 (INI-1)-deficient sinonasal carcinoma is a rare but locally aggressive malignancy of the nasal cavity and paranasal sinuses, representing about only 1 % of all head and neck malignancies. It is characterized by loss of INI-1 in the tumour cells under immunohistochemical staining. The overwhelming majority of INI-1 deficient sinonasal carcinoma presents very late at diagnosis, owing to its very similar clinical presentation to other benign conditions like allergic rhinitis, nasal polyps, chronic sinusitis, and some more common malignancies like human papilloma virus-associated squamous cell carcinoma, extranodal NK/T cells lymphoma, mucosal melanoma. Therefore, complete surgical removal remains very challenging and most of the time impossible.

Currently, aggressive multimodality treatment of INI-1-deficient sinonasal carcinomas is based on experience with other sinonasal malignancies including case series of sinonasal undifferentiated carcinoma. Upfront surgical resection for potentially resectable cases, followed by adjuvant radiation therapy or adjuvant chemoradiation. Also under investigation is the use of induction chemotherapy followed by surgery and adjuvant radiation in the treatment of sinonasal malignancy.

In view of the above, the investigators are now proposing a phase II single-arm study on tazemetostat in combination with TPF as preoperative therapy for locally advanced non-metastatic SMARCB1 (INI-1)-deficient sinonasal carcinoma, followed by radical resection and/or post-operative radiation therapy (with or without concurrent chemotherapy), and tazemetostat for another 6 months. It is hypothesized that addition of tazemetostat will improve objective response rate, resectability rate, orbit preservation rate, and hopefully survival outcomes with manageable safety profiles.

Induction treatment with docetaxel, cisplatin, 5-FU and tazemetostat followed by surgery or radical chemoradiation and maintenance tazemetostat

Induction Chemotherapy and Tazemetostat for Locally Advanced SMARCB1-deficient Sinonasal Carcinoma

A Phase II Single-arm Study of Tazemetostat With Docetaxel, Cisplatin, and 5-fluorouracil as Preoperative Treatment for Locally Advanced Potentially Resectable SMARCB1 (INI-1)- Deficient Sinonasal Carcinoma

There is no plan to make individual participant data (IPD) available to other researchers.

Orbit preservation rate defined as the rate that sums up that of orbit preservation surgery with a clear resection and that of radical chemoradiation after induction TPF and tazemetostat

Incidence of treatment-related side effects as determined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

Dr. Victor H.F. Lee

Clinical Associate Professor

Etoposide

Durvalumab

Etoposide phosphate

SBRT + Concurrent Mediastinal Chemoradiation +/- Consolidation Chemotherapy/Adjuvant Immunotherapy

SBRT

IMRT

John H Heinzerling

This is a single-arm, single-stage Phase II study designed to evaluate the 1-year PFS rate in subjects with locally-advanced NSCLC (stage II/III) and treated with Stereotactic Body Radiation Therapy (SBRT) followed by concurrent mediastinal chemoradiation with or without consolidation chemotherapy. A total of 60 subjects will be enrolled to this study over a 4 year accrual period.

This study's primary objective is to assess the efficacy of a treatment regimen involving Stereotactic Body Radiation Therapy (SBRT) delivered to the primary tumor followed by concurrent mediastinal chemoradiation by evaluating the proportion of subjects with locally-advanced non-small cell lung cancer (NSCLC) stage II/III who are alive and progression free at 12 months, and to compare to relevant historical controls. Additionally, the treatment regimen will be evaluated based on progression free survival, overall survival, radiologic clinical complete response rate following completion of therapy, objective response rate as defined by RECIST v 1.1, local and locoregional control, patterns of failure, and quality of life. Safety objectives include the rate of grade 2+ radiation pneumonitis and grade 3+ pulmonary events. Exploratory objectives include differential expression of cytokines and chemokines associated with radiation therapy will be determined.

Use of High Dose Radiation Followed by Chemotherapy and Radiation to Treat Locally Advanced NSCLC

LCI-LUN-NSC-SBRT-001: Phase II Prospective Trial of Primary Lung Tumor Stereotactic Body Radiation Therapy Followed by Concurrent Mediastinal Chemoradiation and Adjuvant Immunotherapy for Locally-Advanced Non-Small Cell Lung Cancer

Toxicities will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Toxicities will be tabulated by type and grade separately for each phase of treatment.

Progression-free survival (PFS) will be determined for each subject as a binary variable indicating whether or not the subject is alive and progression free at 12 months

Progression free survival (PFS) is defined as the duration of time from enrollment to the study to first occurrence of either progressive disease or death.

Overall survival (OS) is defined as the duration of time from the date of enrollment to the study to the date of death from any cause.

Radiologic clinical complete response will be recorded for each subject as a binary variable indicating whether or not the subject had no evidence of disease on PET/CT or CT scan approximately 3 months after the last treatment of concurrent mediastinal chemoradiation.

Objective response will be determined for each subject as a binary variable indicating whether or not the subject achieved a best overall response of Complete Response (CR) or Partial Response (PR).

Local control (LC) is defined as the duration of time from enrollment to the study to first progression of the subject's primary lesions(s).

Regional control (RC) is defined as the duration of time from enrollment to the study to first progression of the subject's regional lesion(s).

Locoregional control is defined as the duration of time from enrollment to the study to first progression of the subject's local and/or regional lesion(s), whichever occurs first.

Distant control defined as the duration of time from enrollment to the study to first metastatic progression.

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score represents a higher (better) level of functioning, or a higher (worse) level of symptoms.

The QLQ-LC13 includes questions assessing lung cancer associated symptoms, treatment related side effects and pain medication. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score represents a higher (better) level of functioning, or a higher (worse) level of symptoms.

The MDASI-LC Module includes 22 questions to assess the severity of multiple lung cancer-related symptoms and the impact of these symptoms on daily functioning. Scores for each item range from 0 to 10, where 0 indicates no symptoms and 10 indicates worst possible symptoms.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Apatinib Combined With Abraxane and Carboplatin or Cisplatinum as First-line Treatment for Epithelial Ovarian Cancer	NCT04590625	Ovarian Cancer	Apatinib Mesyla... Abraxane Cis Platinum Carboplatin	18 Years - 75 Years	Zhongshan Hospital Xiamen University
Pembrolizumab + Platinum Doublets Without Radiation for Programmed Death-ligand 1 (PD-L1) ≥50% Locally Advanced NSCLC	NCT04153734	Locally Advance...	Pembrolizumab Cis Platinum Carboplatin Pemetrexed nab paclitaxel	-	Kobe Minimally Invasive Cancer Center
Tislelizumab in Combination With Chemotherapy for Conversion Therapy of Locally Nonresectable ESCC	NCT05469061	Esophageal Squa... Locally Advance...	Tislelizumab 5-FU cis Platinum	18 Years - 75 Years	The First Affiliated Hospital with Nanjing Medical University
Pembrolizumab + Platinum Doublets Without Radiation for Programmed Death-ligand 1 (PD-L1) ≥50% Locally Advanced NSCLC	NCT04153734	Locally Advance...	Pembrolizumab Cis Platinum Carboplatin Pemetrexed nab paclitaxel	-	Kobe Minimally Invasive Cancer Center
Induction Chemotherapy and Tazemetostat for Locally Advanced SMARCB1-deficient Sinonasal Carcinoma	NCT05151588	Sinonasal Carci...	Docetaxel Cis Platinum 5-FU Tazemetostat Surgery Chemoradiation	18 Years -	The University of Hong Kong
Use of High Dose Radiation Followed by Chemotherapy and Radiation to Treat Locally Advanced NSCLC	NCT03141359	Lung Cancer Sta... Lung Cancer Sta... Non Small Cell ...	SBRT Carboplatin Paclitaxel cis Platinum Etoposide IMRT Durvalumab	18 Years -	Wake Forest University Health Sciences

Spots Global Cancer Trial Database for cis platinum

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