Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Carcinoma, Non-Small-Cell Lung

Carcinoma

Lung Neoplasms

Recurrence

Disease Progression

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Pembrolizumab

Immunomodulating Agents

Nivolumab

Tyrosine Kinase Inhibitors

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients receive nivolumab IV over 60 minutes every 2 weeks or pembrolizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.

Patients receive tyrosine kinase inhibitor therapy PO targeting the initial oncogenic driver or other treatment for about 3 weeks.

Patients receive tyrosine kinase inhibitor therapy PO targeting initial oncogenic driver, a drug targeting the secondary mutation, or other treatment for about 3 weeks.

Chemotherapy

Immunotherapy

Laboratory Biomarker Analysis

Receive drug targeting secondary mutation

Targeted Molecular Therapy

Tyrosine Kinase Inhibitor

William Petty

This phase II trial studies how well targeted therapy works in treating patients with incurable non-small cell lung cancer with a genetic mutation. Giving drugs that target other genetic mutations or other specific proteins may work better when a patient has cancer caused by a driver mutation and the treatment that targets that mutation stops working.

PRIMARY OBJECTIVES:

I. To estimate the objective response rate among patients with high PD-L1 expressing cancers after failure of targeted therapy.

SECONDARY OBJECTIVES:

I. To compare the overall survival for patients receiving treatment targeting primary mutations, secondary mutations, or immunotherapy at the time of progression on tyrosine kinase inhibitor therapy.

II. To assess the incidence of secondary mutations in this population according to smoking status.

III. To evaluate the response rates of patients treated using these different approaches.

IV. To correlate outcomes with specific secondary genetic changes.

OUTLINE: Patients are assigned to 1 of 3 treatment arms.

ARM I (PD-L1 \>= 50%): Patients receive nivolumab intravenously (IV) over 60 minutes every 2 weeks or pembrolizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.

ARM II (PD-L1 \< 50% without secondary oncogenic driver): Patients receive tyrosine kinase inhibitor therapy orally (PO) targeting the initial oncogenic driver or other treatment for about 3 weeks.

ARM III (PD-L1 \< 50% with secondary oncogenic driver): Patients receive tyrosine kinase inhibitor therapy PO targeting initial oncogenic driver, a drug targeting the secondary mutation, or other treatment for about 3 weeks.

After completion of study treatment, patients are followed up for a minimum of 30 days.

Targeted Therapy in Treating Patients With Incurable Non-Small Cell Lung Cancer With Genetic Mutations

Phase II Pilot Study Evaluating Strategies to Overcome Resistance at the Time of Progression for Patients With Non-small Cell Lung Cancers Harboring Major Oncogenic Drivers

Toxicities for each group will be estimated and described using counts and frequencies by grade, location and relatedness.

Objective response rates will be estimates in the two PD-L1 expression \< 50% arms. Confidence intervals for each of these rates will be estimated. An exploratory comparison will be made among the three groups comparing complete response/partial response versus stable disease/progressive disease among the groups using a Fisher's exact test (for the 2x3 table).

Estimated using Kaplan-Meier methods and survival rates will be compared using log-rank tests.

Whether smoking status is related to the prevalence of any mutations identified (present/absent) will be examined using Cochran-Maentel Haenzel tests. These tests will be performed overall and then separately in the three arms.

National Cancer Institute (NCI)

Wake Forest University Health Sciences

Immunologic Factors

immunotherapy

Targeted Therapy Agent

Xiaomin Niu

Psychological distress is a multi-factorial experience of a psychological, social, spiritual, and/or physical nature that may interfere with one's ability to cope effectively with cancer, physical symptoms and treatment. Psychological distress is common and affects the efficacy and prognosis of patients with lung cancer. The systematic anti-tumor therapy may effectively relieve psychological distress including anxiety, depression, and fatigue in patients with advanced lung cancer, the relief of the psychological distress can in turn improve the therapeutic effect.

In summary, this study is to explore the associations of (dynamic) psychological stress with the efficacy and survival of anti-tumor therapy including immunotherapy and targeted therapy for advanced lung cancer patients.

Association of Psychological Distress in Patients With Lung Cancer

the Association of Psychological Distress in Patients With Advanced Lung Cancer Treated With Immunotherapy or Targeted Therapy

Collect detailed clinical information on patients with SCLC via the electronic medical records

Shanghai Chest Hospital

Principal Investigator

Trastuzumab

Bevacizumab

Pertuzumab

Vemurafenib

Based on next-generation sequencing (NGS) detection, after discussion by the Molecular Steering Committee (MTB), intervention guidance suggestions are given based on domestic and foreign guidelines and clinical experience, and finally the patient and clinician jointly choose the treatment plan.

Targeted therapy

Zhiyuan Xu, MD

Yongmei Li, MD

Weitang Wu

This is a prospective registration study for patients with advanced refractory solid tumors. Patients who meet the eligibility criteria will be included to participate in the study, and baseline information to be collected after signed informed consent. Patients will choose for themselves whether to carry out targeted therapy or other appropriate treatment methods. And we plan to follow up for at least 12 months or until disease progression or death.

1. Screen and enroll 120 patients with refractory solid tumors, and sign informed consents;
2. Extract the clinical data, including gender, age, disease diagnosis, past treatment history and genetic test results, etc.;
3. Take biopsy samples and perform NGS testing on patients. After discussion by the Molecular Steering Committee (MTB), the recommendations for treatment guidance will be given based on treatment guidelines and clinical experience;
4. The patient and the clinician jointly select the treatment plan and follow-up until the patient's disease progresses. The follow-up time will be 1 year;
5. During the follow-up period, clinical treatment and routine examination information of patients will be collected;
6. If the patient fails to receive molecular targeted therapy or they cannot tolerate the adverse reaction of the drug after adequate treatment, the clinician will evaluate whether a second NGS resistance test is needed or the participant may withdraw from the study.

The patient undergoes biopsy sampling for next-generation sequencing (NGS) testing.

a Prospective Registration Study for Patients With Advanced Refractory Solid Tumors

Patients With Advanced Refractory Solid Tumors Who Failed Standard Treatments and Matched Individualized Treatment Based on Tumor Molecular Characteristics: a Prospective Registration Study

We compare the ECOG scores of each visit with the baseline, including the number and proportion, and the difference.

After targeted therapy drug resistance, then the proportion of targeted therapy guided by the second tumor molecular characteristics would be calculated during study period.

ORR is judged based on RECIST 1.1 criteria for all treatment groups at each visit period.

The proportion of all enrolled patients receiving targeted therapy guided by tumor molecular characteristics during the study period, would be calculated, which defined as having received one or more the treatments based on tumor molecular characteristics.

PFS is defined as the time from the first administration to disease progression or death.

OS is defined as the time from the first administration to death from any cause.

The effectiveness of a patient would be evaluated multiple times, and the best one is defined as the best overall response.

The incidence of serious adverse events in each group, which is judged based on CTCAE v5.0 standard.

The QoL is evaluated by the scale (0PROMIS-29 Profile v2.1) at each visit period for all the enrolled patients.

The intervening genomic variants are defined by the conclusion after MTB discussion.

Tianjin Happy Life Technology Co., Ltd.

The University of Hong Kong-Shenzhen Hospital

Digestive System Diseases

Rare Diseases

Biliary Tract Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Biliary Tract Cancer

Capecitabine

Apatinib

Antimetabolites

Camrelizumab was administered 200mg iv every 3 weeks. Capecitabine was administered 1000mg/m2 orally, b.i.d. every 3 weeks (Day 1-14 of a treatment cycle) Apatinib:A safety-run-in was conducted in the first cycle to identify the recommended dose of Apatinib, the initial dose was administered 250mg orally daily every 3 weeks (Day 1-14 of a treatment cycle). The dose of Apatinib increase and reduction was 250 mg orally q.d. and 250 mg orally q.o.d. every 3 weeks respectively according to the number of doses limiting toxicity events (DLTs) in the initial group. The final dose of Apatinib for the extension stage was detemained by the result of safety-run-in stage.

Camrelizumab was administered 200mg iv every 3 weeks.

Camrelizumab

Apatinib A safety-run-in was conducted in the first cycle to identify the recommended dose of Apatinib, the initial dose was administered 250mg orally daily every 3 weeks (Day 1-14 of a treatment cycle) The dose of Apatinib increase and reduction was 250 mg orally q.d. and 250 mg orally q.o.d. every 3 weeks respectively according to the number of doses limiting toxicity events (DLTs) in the initial group.

The final dose of Apatinib for the extension stage was detemained by the result of safety-run-in stage.

apatinib

Capecitabine was administered 1000mg/m2 orally, b.i.d. every 3 weeks (Day 1-14 of a treatment cycle)

Wei Deng

Biliary tract cancer (BTC) is a series of rare malignancies with poor overall prognosis. Radical surgery the preferred treatment option, but most patients have lost the opportunity of surgery at the time of diagnosis. At present, there are limited systematical treatment options for biliary tract cancer, with poor efficacy and short duration of responses. In the past few years, immune checkpoint inhibitors (ICIs) therapy has gradually been added to the advanced biliary comprehensive treatment. However, in view of the low incidence and high heterogeneity of BTC, more large number of clinical trials and practices need to be carried out, and the effective combination regimens and predictive biomarkers need to be explored. This study is a single-arm, open-label, prospective cohort study, combining Camrelizumab with apatinib and capecitabine as the first-line or second-line treatment for patients with advanced biliary tract cancer. The study aims to explore the efficacy and safety of the combination regimen, and try to find biomarkers that can guild treatment. In this study, 34 patients were enrolled by the Simon's two-stage design, with the objective response rate as the primary endpoint and the disease control rate, progression-free survival, overall survival and safety as secondary endpoints. It is expected that the three-drug combination regimen will have significant efficacy and manageable adverse reactions, and predictive biomarkers can be found.

Camrelizumab Combined With Apatinib and Capecitabine in Patients With Advanced Biliary Tract Cancer.

Camrelizumab Combined With Apatinib and Capecitabine for Patients With Advanced Biliary Tract Cancer: a Phase 2, Single-arm, Prospective Study.

IPD can be obtained with the consent of the principal investigator

The proportion of patients with measurable disease who achieved complete response (CR) or partial response (PR)

The proportion of patients achieving CR or PR or stable disease (SD)

The duration from the beginning of the treatment to the disease progression, or death from any cause, or last progression-free survival assessment for patients alive without progression

The duration from the enrollment to death from any cause

The incidence of any grade treatment-related adverse events.

Beijing Friendship Hospital

professor

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Sunitinib

Angiogenesis Inhibitors

Growth Inhibitors

Beginning 4-12 weeks following radical nephrectomy, patients receive sunitinib malate PO QD for 4 weeks

Patients with radical nephrectomy are observed without intervention

The investigators randomly assign assay-defined high risk patients of stageIII ccRCC into intervention group and observation group. The intervention group should receive adjuvant targeted therapy while the control group deserve observation.

sunitinib

Jinhuan Wei, MD

Jun-Hang Luo, MD

Whether patients with stage III clear cell renal cell carcinoma(ccRCC) should receive adjuvant targeted therapy or not is still on debate. The investigators invented a assay consisting of 5 CpGs: cg00396667（PITX1）, cg18815943 （FOXE3）, cg03890877（TWF2）, cg07611000 （EHBP1L1）and cg14391855（RIN1）that was successfully categorise patients with stage III clear cell renal cell carcinoma into high-risk and low-risk groups with Harzard Ratio(HR) of 4.93. Here the investigators randomly assign assay-defined high risk patients of locally advanced ccRCC into adjuvant targeted therapy group and observation group.Disease free survival and overall survival are the end points of observation.

The investigators' CpG-methylation-based assay contains 5 CpGs: cg00396667（PITX1）, cg18815943 （FOXE3）, cg03890877（TWF2）, cg07611000 （EHBP1L1）and cg14391855（RIN1）. The investigators evaluate the CpG methylation status of surgical specimens using pyrosequencing and calculate their risk score\[risk score=(0.0066×PITX1)+(0.0034×FOXE3)-(0.027×TWF2) -(0.018×EHBP1L1)-(0.03×RIN1)\], risk score ≥-0.1 as assay-defined high risk status and risk score\<-0.1 as assay-defined low risk status. The investigators randomly assign assay-defined high risk patients of stage III ccRCC into intervention group and control group. The intervention group should receive adjuvant targeted therapy while the control group deserve observation. Primary endpoint is the disease free survival and overall survival.

A CpG-methylation-based Assay for Stratifying Stage III Clear Cell Renal Cell Carcinoma of Receiving Adjuvant Treatment

A Multi-site, Open, Perspective Study of Prognostic Value and Benefit From Adjuvant Targeted Therapy of Stage III Clear Cell Renal Cell Carcinoma Based on a CpG-methylation-based Assay

Health Science Center of Xi'an Jiaotong University

Yantai Yuhuangding Hospital

Sun Yat-sen University

First Affiliated Hospital, Sun Yat-Sen University

Professor

Glioblastoma

Gliosarcoma

Disease Attributes

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroepithelioma

Patients receive NU-0129 IV over 20-50 minutes and undergo standard of care tumor resection within 8-48 hours.

Pharmacological Study

Priya Kumthekar, MD

The purpose of this research study is to evaluate the safety of the study drug, NU-0129, based on Spherical Nucleic Acid (SNA) platform when infused in patients with recurrent glioblastoma multiforme or gliosarcoma. The SNA consists of nucleic acids arranged on the surface of a small spherical gold nanoparticle. This is a first-in-human trial to determine the safety of NU-0129. NU-0129 can cross the blood brain barrier (a filtering mechanism that carry blood to the brain). Once within the tumor, the nucleic acid component is able to target a gene called Bcl2L12 that is present in glioblastoma multiforme, and is associated with tumor growth. This gene prevents tumor cells from apoptosis, which is the process of programmed cell death, thus promoting tumor growth. Researchers think that targeting the Bcl2L12 gene with NU-0129 will help stop cancer cells from growing.

PRIMARY OBJECTIVES:

I. To assess the safety of intravenous NU-0129 in patients with recurrent glioblastoma multiforme (GBM) or gliosarcoma (GS).

SECONDARY OBJECTIVES:

I. To analyze drug concentration in serum at specific time points after drug administration.

II. To demonstrate intratumoral penetration of NU-0129. III. To assess the feasibility of giving NU-0129 as a standard treatment for recurrent GBM or GS.

TERTIARY OBJECTIVES:

I. To analyze tumor tissue for Bcl2L12 expression levels after NU-0129 administration.

II. Preliminary response (progression free survival \[PFS\] and overall survival \[OS\] at 6 months; overall response rate \[ORR\]).

OUTLINE:

Patients receive NU-0129 intravenously (IV) over 20-50 minutes and undergo standard of care tumor resection within 8-48 hours.

After completion of study treatment, patients are followed up at 7, 14, 21, and 28 days and then every 84 days for up to 2 years.

NU-0129 in Treating Patients With Recurrent Glioblastoma or Gliosarcoma Undergoing Surgery

A Phase 0 First-In-Human Study Using NU-0129: A Spherical Nucleic Acid (SNA) Gold Nanoparticle Targeting BCL2L12 in Recurrent Glioblastoma Multiforme or Gliosarcoma Patients

To evaluate the safety of intravenous NU-0129 in patients with recurrent GBM or GS, the number of adverse events will be assessed and will be graded according to the NCI's Common Terminology Criteria in Adverse Events (CTCAE) version 4.03 where the grading is as follows:

Grade 1: Mild Grade 2: Moderate Grade 3: Severe Grade 4: Life-threatening Grade 5: Fatal

Blood samples will be collected post-infusion to analyze drug concentration at specific time points after drug administration. Median plasma concentrations of NU-0129 were derived from time profiles for both Seven different small interfering RNA (siRNA) and gold (Au) concentrations, with Au plasma concentration determined by inductively coupled plasma mass spectrometry (ICP-MS) and siRNA concentration assessed by liquid chromatography-high performance liquid chromatography (LC-HPLC) using an atto dye-labeled PNA probe.

Tissue will be collected during the scheduled surgery and assayed with Inductively Coupled Plasma Mass Spectrometry (ICP-MS) to analyze the concentration of particles in various parts of tumor tissue. To analyze spatial distribution of Au within tumor tissue, synchrotron XFM elemental maps of GBM tissue slices were acquired at micron and submicron resolution and matched to adjacent hematoxylin and eosin (H\&E)- and Ki67-stained tumor sections. Approximate percentage of gold (Au) found in cancer cells is reported below.

Feasibility will be calculated as the rate of successful production, delivery, and administration of the investigational product and subsequent resection.

Northwestern University

NU-0129 will be administered inpatient at \~ 0.04mg/kg IV 8-48 hours once prior to scheduled tumor resection. Dose corresponds to 1/50th of the no-observed-adverse-event level.

NU-0129 Treatment

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Priya Kumthekar

Experienced any AE

Experienced an AE related to NU-01289

Experienced any SAE

Experienced an SAE related to NU-0129

Number of Patients With Adverse Events

siRNA maximum observed plasma concentration

Au maximum observed plasma concentration

NU-0129 Concentration in Blood After Drug Administration Using Maximum Concentration

2 patients tumor resections resulted in insufficient amount of viable tumor tissue for ICP-MS analysis and were not included in this analysis

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Targeted Therapy in Treating Patients With Incurable Non-Small Cell Lung Cancer With Genetic Mutations	NCT02949843	EGFR Activating... Recurrent Non-S... Stage IV Non-Sm...	Chemotherapy Immunotherapy Laboratory Biom... Nivolumab Pembrolizumab Targeted Molecu... Tyrosine Kinase...	-	Wake Forest University Health Sciences
Association of Psychological Distress in Patients With Lung Cancer	NCT06218901	Lung Neoplasms Psychological D... Prognosis Facto... Lifestyle, Heal... IMMUNOTHERAPY Targeted Molecu...	immunotherapy Targeted Therap...	18 Years -	Shanghai Chest Hospital
Association of Psychological Distress in Patients With Lung Cancer	NCT06218901	Lung Neoplasms Psychological D... Prognosis Facto... Lifestyle, Heal... IMMUNOTHERAPY Targeted Molecu...	immunotherapy Targeted Therap...	18 Years -	Shanghai Chest Hospital
a Prospective Registration Study for Patients With Advanced Refractory Solid Tumors	NCT05177666	Feasibility Effectiveness Safety Targeted Molecu...	Targeted therap...	18 Years -	The University of Hong Kong-Shenzhen Hospital
Camrelizumab Combined With Apatinib and Capecitabine in Patients With Advanced Biliary Tract Cancer.	NCT04720131	Biliary Tract C... Anti-PD-1 Thera... Targeted Molecu... Capecitabine	Camrelizumab apatinib Capecitabine	18 Years - 85 Years	Beijing Friendship Hospital
Targeted Therapy in Treating Patients With Incurable Non-Small Cell Lung Cancer With Genetic Mutations	NCT02949843	EGFR Activating... Recurrent Non-S... Stage IV Non-Sm...	Chemotherapy Immunotherapy Laboratory Biom... Nivolumab Pembrolizumab Targeted Molecu... Tyrosine Kinase...	-	Wake Forest University Health Sciences
Association of Psychological Distress in Patients With Lung Cancer	NCT06218901	Lung Neoplasms Psychological D... Prognosis Facto... Lifestyle, Heal... IMMUNOTHERAPY Targeted Molecu...	immunotherapy Targeted Therap...	18 Years -	Shanghai Chest Hospital
A CpG-methylation-based Assay for Stratifying Stage III Clear Cell Renal Cell Carcinoma of Receiving Adjuvant Treatment	NCT02688491	Renal Neoplasms Targeted Molecu...	sunitinib	18 Years - 75 Years	First Affiliated Hospital, Sun Yat-Sen University
NU-0129 in Treating Patients With Recurrent Glioblastoma or Gliosarcoma Undergoing Surgery	NCT03020017	Gliosarcoma Recurrent Gliob...	Laboratory Biom... Pharmacological... Targeted Molecu...	18 Years -	Northwestern University

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