Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Rare Diseases

Small Cell Lung Carcinoma

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

All Drugs and Chemicals

Thymalfasin

Adjuvants, Immunologic

Immunologic Factors

Patients with metastatic lesions of small cell lung cancer receiving 3.5Gy per fraction to a total dose of 35Gy/10 fractions over 2 weeks with concurrent thymalfasin.

3.5Gy per fraction to a total dose of 35Gy/10 fractions over 2 weeks with concurrent thymalfasin for metastatic lesions of small cell lung cancer.

Radiotherapy

Patients with metastatic lesions of small cell lung cancer receiving 3.5Gy per fraction to a total dose of 35Gy/10 fractions over 2 weeks with concurrent thymalfasin ( given twice a week with an interval of 3-4 days each week).

Shixiu Wu, MD

Patients with small cell lung cancer that had metastatic lesions after been treated with definitive surgery or chemoradiotherapy are being asked to participate in this study.

1. To observe immunity-mediated tumor response outside the radiation field (abscopal effect) after chemoradiotherapy of a metastatic site in metastatic small cell lung cancer patients.
2. To induce the efficacy (effectiveness) of a new combination of therapy, chemoradiotherapy and thymalfasin for heavily pretreated, metastatic small cell lung cancer patients;
3. To explore the role of PET/CT scanning to assess tumor response/abscopal effect.

This study will help find out what abscopal effects (good or bad) the combination of radiotherapy and thymalfasin has on metastatic small cell lung cancer.

1. To observe immunity-mediated tumor response outside the radiation field (abscopal effect) after chemoradiotherapy of a metastatic site in metastatic small cell lung cancer patients.
2. To induce the efficacy (effectiveness) of a new combination of therapy, chemoradiotherapy and thymalfasin for heavily pretreated, metastatic small cell lung cancer patients;
3. To explore the role of PET/CT scanning to assess tumor response/abscopal effect.

Eligible are patients with metastatic small cell lung cancer who have achieved stable disease or have disease progression after systemic therapy (surgery or definitive chemoradiotherapy) and have at least three separate measurable sites of metastatic lesions. Extent of metastatic disease is recorded both at CT and PET/CT scanning. Radiation is given during combined therapy to one of the lesions, 35Gy in 10 fractions over a two week interval, conformally to maximally spare normal tissue or organ. Thymalfasin treatment is given twice a week with an interval of 3-4 days each week. At day 22 radiation is re-started and the same radiation dose is delivered to a second metastatic site, again with thymalfasin. Abscopal response is evaluated by assessing clinical and PET/CT response in the non-irradiated measurable metastatic sites. A Phase II clinical trial based on an optimum two-stage Phase II Simon design is used to conduct this pilot study. Ten patients will be treated in Stage one; if there are no abscopal responses, the trial will be terminated. If there are one or more abscopal responses in Stage One, the trial will proceed to enroll an additional 19 patients.

Abscopal Effect for Metastatic Small Cell Lung Cancer

A Phase II Study of Radiotherapy and ZADAXIN's® (Thymalfasin) Induced Abscopal Effect in Patients With Heavily Pretreated, Metastatic Small Cell Lung Cancer

Zhejiang Provincial People's Hospital

Antineoplastic Agents

Doxorubicin

Liposomal doxorubicin

Topotecan

Topoisomerase I Inhibitors

Enzyme Inhibitors

230 mg/m2 (170 mg/m2 doxorubicin equivalent) intravenously on Day 1 of each 21-day cycle. Number of cycles: until tumor progression or unacceptable toxicity occurs.

Aldoxorubicin

1.5 mg/m2/day intravenously for 5 consecutive days on Day 1 of each 21-day cycle OR 4 mg/m2 intravenously on Days 1, 8 and 15 of each 28-day cycle. Number of cycles: until tumor progression or unacceptable toxicity occurs

Cynthia Martin

Alain Mita, M.D.

New Patient Services

Marianna Koczywas, M.D.

Melissa Rammage

Augusto Villegas, M.D.

Melissa Lee

Robert Hermann, M.D.

Jennifer Schoenbachler

Goetz Kloecker, M.D.

Patient Hotline

David Waterhouse, M.D.

Rhonda Stephenson

Abdul Hai Mansoor, M.D

Heather Austin

Chandra Belani, M.D.

Hotline

Davey Daniel, M.D.

Susie Owen

Russel DeVore, M.D.

Daphne Hubbard

Ray Page, M.D.

Katalin Udud

Katalin Udud, M.D.

Erzsebet Juhasz

Ildiko Horvath, M.D.

Maria Szilasi

Maria Szilasi, M.D.

Peter Szabo

Peter Szabo, M.D.

Veronika Sarosi

Veronika Sarosi, M.D.

Tibor Csoszi

Tibor Csoszi, M.D.

Bartomeu Massuti

Bartomeu Massuti, M.D.

Noemi Reguart

Noemi Reguart, M.D.

Rafael Rosell

Rafael Rosell, M.D.

Alejandro Navarro

Alejandro Navarro, M.D.

Natlia Fernandez

Natlia Fernandez, M.D.

Ramon Garcia Gomez

Ramon Garcia Gomez, M.D.

Mariano Provencio Pulla

Mariano Provencio Pulla, M.D.

Manuel Domine Gomez

Manuel Domine Gomez, M.D.

Javier De Castro

Javier De Castro, M.D.

Vanesa Gutierrez

Vanesa Gutierrez, M.D.

Reyes Bernabe Caro

Reyes Bemabe Caro, M.D

Martin Lazaro

Martin Lazaro, M.D.

The purpose of this study is to evaluate the efficacy and safety of aldoxorubicin compared to topotecan in subjects with metastatic small cell lung cancer.

Efficacy and Safety of Aldoxorubicin Compared to Topotecan in Subjects With Metastatic Small Cell Lung Cancer

A Multicenter, Randomized, Open-Label Phase 2b Study to Investigate the Efficacy and Safety of Aldoxorubicin Compared to Topotecan in Subjects With Metastatic Small Cell Lung Cancer Who Either Relapsed or Were Refractory to Prior Chemotherapy

PFS is defined as the time from the date of randomization to first documentation of objective tumor progression or to death due to any cause in the absence of previous documentation of objective tumor progression.

Overall survival is defined as the time from randomization to date of death. In the absence of confirmation of death, survival time will be censored at the last date the subject is known to be alive.

The safety of aldoxorubicin compared to topotecan in this population assessed by the frequency and severity of adverse events (AEs), abnormal findings on physical examination, laboratory tests, vital signs, echocardiogram (ECHO) evaluations, electrocardiogram (ECG) results, and weight, as well as disease control rate and tumor response.

CytRx

Digestive System Diseases

Skin and Connective Tissue Diseases

Carcinoma, Non-Small-Cell Lung

Carcinoma, Hepatocellular

Sarcoma

Melanoma

Sarcoma, Alveolar Soft Part

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Neoplasms, Connective and Soft Tissue

Soft Tissue Sarcoma

Alveolar Soft Part Sarcoma

Neuroendocrine Tumor

Neuroepithelioma

Immunomodulating Agents

Atezolizumab

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Atezolizumab administered via IV at either 1,200 mg q3 weeks, or 1,680 mg q4 weeks for the first 2 doses followed by 850mg q2 weeks or q6 weeks.

NCI Medical Oncology Referral Office

James L Gulley, M.D.

National Cancer Institute Referral Office

Background:

A type of drug called monoclonal antibody immune checkpoint inhibitors are often used in cancer treatment. These drugs help the body s immune system fight cancer by blocking proteins that cause cancer cells to grow. One of these drugs (atezolizumab) is approved to treat certain cancers. Researchers want to find out if lower doses of this drug might provide the same benefit with fewer adverse effects.

Objective:

To test different doses and timing of atezolizumab for people with cancer.

Eligibility:

People aged 18 years and older with cancer that has spread locally or to other organs. They must be eligible for treatment with the study drug.

Design:

Participants will be screened. They will have blood tests and imaging scans. They will provide a sample of tissue from their tumor.

Atezolizumab is administered through a tube attached to a needle inserted into a vein in the arm. Participants will take this drug alone or combined with other drugs prescribed for their care.

The first 2 treatments will be done per the FDA recommended dose and schedule. Before administering the second dose of the study drug, researchers will check the level of the drug in the participant s blood. Depending on those results, their 3rd dose will be scheduled 2 to 6 weeks later.

For the 3rd dose of the study drug, participants will switch to the FDA minimum dosage. Dosages of any other drugs will not change.

Researchers will continue to test the levels of the drug in participants blood before each treatment for 16 weeks. After that, these levels will be tested every 3 months.

Study treatment may last up to 2 years.

Background:

* The treatment of many cancers has been revolutionized through the use of monoclonal antibody immune checkpoint inhibitor drugs, particularly those that block the interaction of the anti-programmed death-ligand 1 (PD-L1) with the programmed death-1 (PD-1) receptor.
* Atezolizumab was initially tested in a phase 1a multicenter, dose-escalation, and dose- expansion study (NCT01375842) which showed that the drug was well tolerated and produced clinical responses in a variety of tumors.
* The initially approved atezolizumab regimen was 1,200 mg every 3 weeks, but 840 mg every 2 weeks was added based on the data from the TNBC trial (NCT01375842). This was taken further by Morrissey et al., who used population pharmacokinetic (PK) simulations to determine that dosing regimens of 840 mg every 2 weeks and 1,680 mg every 4 weeks are interchangeable with 1,200 every 3 weeks in terms of efficacy, leading the Food and Drug Administration (FDA) to expand the dosing regimens for atezolizumab.
* The standard dosing regimens yield steady-state concentrations greater than 10-fold above the stated minimum effective concentration of 6 g/mL, to ensure adequate exposure for all patients, including patients that may experience lower exposure due to the incidence of anti-drug-antibodies (ADA). Atezolizumab exhibits a flat exposure- response relationship.

Objective:

-To test the feasibility of reducing drug exposure while maintaining plasma drug concentration at or above the expected target trough value during a 16-week study period by using a method for therapeutic drug monitoring of atezolizumab.

Eligibility:

* Age \>= 18 years old.
* Participants with a locally advanced or metastatic cancer who are candidates for treatment with atezolizumab, either alone or in combination with other FDA-approved drug(s).
* Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2.
* Adequate organ and marrow function.

Design:

* This is a phase I feasibility study of a therapeutic drug monitoring (TDM)-based method for atezolizumab dosing.
* The participants will start with FDA approved dose and frequency of atezolizumab (840 mg every 2 weeks, 1,200 mg every 3 weeks, or 1,680 mg every 4 weeks) selected by their treating physician for the first two doses of the drug per standard of care.
* After the second dose, starting at 3rd dose, the dose of the drug will be switched to 840 mg and will be used going forward in the trial in all participants.
* Prior to each dose, starting at the 2nd dose, a trough will be drawn which will be by the population PK model to predict the timing of the next dose to maintain the atezolizumab target trough for each participant specifically. This will be repeated for the first 16 weeks of treatment.
* After 16 weeks of treatment, the timing of the next dose to maintain the atezolizumab target trough for each participant will be monitored and adjusted (if necessary) every 3 months for each participant until 2 years.

A Study of Therapeutic Drug Monitoring-Based Atezolizumab Dosing

A Feasibility Multicenter Phase I Study of Therapeutic Drug Monitoring-Based Atezolizumab Dosing

The fraction of participants that can be dosed with 840mg of atezolizumab at less frequent intervals while maintaining a trough PK concentration at or above 6 mg/mL

PK evaluations before every atezolizumab infusion starting from the second dose until 16 weeks after atezolizumab treatment and every 3 months after 16 weeks on treatment.

National Cancer Institute (NCI)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Abscopal Effect for Metastatic Small Cell Lung Cancer	NCT02542137	Small Cell Lung... Radiotherapy Thymalfasin	Radiotherapy Thymalfasin	19 Years -	Zhejiang Provincial People's Hospital
Efficacy and Safety of Aldoxorubicin Compared to Topotecan in Subjects With Metastatic Small Cell Lung Cancer	NCT02200757	Metastatic Smal...	Aldoxorubicin Topotecan	18 Years -	CytRx
Efficacy and Safety of Aldoxorubicin Compared to Topotecan in Subjects With Metastatic Small Cell Lung Cancer	NCT02200757	Metastatic Smal...	Aldoxorubicin Topotecan	18 Years -	CytRx
A Study of Therapeutic Drug Monitoring-Based Atezolizumab Dosing	NCT06066138	Locally Advance... Metastatic Alve... Locally Advance... Metastatic Non ... Locally Advance... Metastatic Smal... Locally Advance... Metastatic Hepa... Locally Advance... Metastatic Mela...	Atezolizumab	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
A Study of Therapeutic Drug Monitoring-Based Atezolizumab Dosing	NCT06066138	Locally Advance... Metastatic Alve... Locally Advance... Metastatic Non ... Locally Advance... Metastatic Smal... Locally Advance... Metastatic Hepa... Locally Advance... Metastatic Mela...	Atezolizumab	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Abscopal Effect for Metastatic Small Cell Lung Cancer	NCT02542137	Small Cell Lung... Radiotherapy Thymalfasin	Radiotherapy Thymalfasin	19 Years -	Zhejiang Provincial People's Hospital
A Study of Therapeutic Drug Monitoring-Based Atezolizumab Dosing	NCT06066138	Locally Advance... Metastatic Alve... Locally Advance... Metastatic Non ... Locally Advance... Metastatic Smal... Locally Advance... Metastatic Hepa... Locally Advance... Metastatic Mela...	Atezolizumab	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for metastatic small cell lung cancer