Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Lung Neoplasms

Carcinoma

Recurrence

Small Cell Lung Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Small Cell Lung Cancer

Antineoplastic Agents

All Drugs and Chemicals

Irinotecan

Topoisomerase I Inhibitors

Etirinotecan pegol

Enzyme Inhibitors

Patients receive pegylated irinotecan NKTR 102 IV over 90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity

Laboratory Biomarker Analysis

Pegylated Irinotecan

Pharmacological Study

Hongbin Chen, MD

This phase II trial studies how well pegylated irinotecan NKTR 102 works in treating patients with small cell lung cancer that has returned after a period of improvement. Pegylated irinotecan NKTR 102 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To evaluate the 18-week progression free survival (PFS) rate of relapsed small cell lung cancer (SCLC) patients treated with NKTR-102 (pegylated irinotecan NKTR 102).

SECONDARY OBJECTIVES:

I. To evaluate the objective response rate. II. To evaluate the duration of response. III. To evaluate the overall survival. IV. To evaluate the toxicity of NKTR-102 in this patient population.

TERTIARY OBJECTIVES:

I. To explore the correlation between UDP glucuronosyltransferase 1 family, polypeptide A cluster (UGTIA1) polymorphisms and NKTR-102 toxicities.

OUTLINE:

Patients receive pegylated irinotecan NKTR 102 intravenously (IV) over 90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.

Pegylated Irinotecan NKTR 102 in Treating Patients With Relapsed Small Cell Lung Cancer

A Phase II Study of Single Agent Topoisomerase-I Inhibitor Polymer Conjugate, Etirinotecan Pegol (NKTR-102), in Patients With Relapsed Small Cell Lung Cancer

The distribution of time to disease progression will be estimated in each group using the method of Kaplan-Meier at 18 weeks.

Objective tumor response will be tabulated overall (and by dose level if appropriate). Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in the cohorts (overall and by tumor group).

The mean duration of response for those participants that responded to treatment by arm.

Count of participants by best response, defined as best objective status recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since treatment started), measured by RECIST 1.1

Tumor response is defined as a complete response (CR) or partial response (PR) by RECIST 1.1 criteria, which will be evaluated by CT scan every other cycle. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

The distribution of survival time was be estimated in each group using the method of Kaplan-Meier.

Count of participants by maximum graded according to NCI CTCAE v 4.0 of any adverse event by arm.

Please refer to the adverse event reporting for more detail.

National Cancer Institute (NCI)

Nektar Therapeutics

Roswell Park Cancer Institute

Group A: chemo resistant - those progressing on first-line therapy \< 3 months after completion of treatment.

Treatment (pegylated irinotecan NKTR 102) Patients receive pegylated irinotecan NKTR 102 IV over 90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity

Laboratory Biomarker Analysis: Correlative studies Pegylated Irinotecan: Given IV Pharmacological Study: Correlative studies

A: Chemo Resistant

Group B: chemo sensitive - those progressing on first-line therapy ≥ 3 months after completion of treatment.

Treatment (pegylated irinotecan NKTR 102) Patients receive pegylated irinotecan NKTR 102 IV over 90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity

Laboratory Biomarker Analysis: Correlative studies

Pegylated Irinotecan: Given IV

Pharmacological Study: Correlative studies

B: Chemo Sensitive

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

ECOG Performance Status: Developed by the Eastern Cooperative Oncology Group GRADE 0 -Fully active, able to carry on all pre-disease performance without restriction, GRADE 1 -Restricted in physically strenuous activity but ambulatory and able to carry out work of light or sedentary nature, GRADE 2 -Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours, GRADE 3 -Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours, GRADE 4 -Completely disabled, GRADE 5 -Dead

ECOG performance status

Senior Administrator, Compliance - Clinical Research Services

18 Week Progression-free Survival Rate

Objective Tumor Response Measured With Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

All participants that responded to treatment

Mean Duration of Response

Best Response

Median Overall Survival

Incidence of Adverse Events, Assessed Using NCI CTCAE v 4.0

Overall Study

Patients receive selinexor PO twice weekly. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Selinexor

Erin Bertino, MD

This phase II trial studies how well selinexor work in treating patients with small-cell lung cancer that has returned after a period of improvement. One specific way cancer cells continue to grow is by getting rid of certain proteins called "tumor suppressor proteins: that would normally cause cancer cells to die. Selinexor works by trapping "tumor suppressing proteins" within the cell and may cause the cancer cells to die or stop growing.

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of single agent selinexor as measured by progression free survival (PFS) in patients with relapsed chemotherapy-sensitive small cell lung cancer.

SECONDARY OBJECTIVES:

I. To evaluate the objective tumor response rate and disease control rate as determined by radiographic response.

II. To evaluate the overall survival (OS) in patients with relapsed small cell lung cancer.

III. To evaluate safety and tolerability of single agent selinexor in these patient populations.

IV. Comparison between each patient's time to progression (TTP) on selinexor with the TTP of his/her previous therapy(ies).

V. To evaluate correlative endpoints including tumor biopsy and analysis of secreted factors, leukocyte ribonucleic acid (RNA) analysis.

TERTIARY OBJECTIVES:

I. Analysis of secreted factors (nerve growth factor \[NGF\], brain-derived neurotrophic factor \[BDNF\]).

II. Tumor biopsy (baseline and cycle 2).

OUTLINE:

Patients receive selinexor orally (PO) twice weekly. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up monthly for 3 months, every 3 months for 1 year, and then every 6 months thereafter.

Selinexor in Treating Patients With Relapsed Small Cell Lung Cancer

An Investigator-Sponsored Phase 2 Study of Single Agent Selinexor (KPT-330) in Patients With Relapsed Small Cell Lung Cancer

Estimated by the method of Kaplan and Meier for each cohort. Appropriate one-sided 90% confidence boundary will also be calculated for the final test Kaplan-Meyer test statistic at 12 weeks.

The overall response rate will be calculated as the number of PRs and CRs divided by the total number of evaluable patients. Estimates will be accompanied by exact binomial confidence intervals as well.

Estimates will be accompanied by exact binomial confidence intervals.

Kaplan-Meier curves will be used to estimate overall survival. Consider Cox proportional hazards models to explore a limited set of confounding factors.

Summarized by descriptive statistics for each of the disease cohorts. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. In addition, review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing.

The incidence of severe (grade 3+) adverse events or toxicities will be described.

Karyopharm Therapeutics Inc

Erin Bertino

Principal Investigator

Frequency and severity of adverse events and tolerability of the regimen were collected and summarized by descriptive statistics for each of the disease cohorts. As per NCI CTCAE v4.0, the term toxicity is defined as adverse events that are classified as either not related, possibly, probably, or definitely related to study treatment.

Arm A: Selinexor (KPT-330)

Ethnicity (NIH/OMB)

United States

Region of Enrollment

Trial was closed early due to slow accrual.

Patients receive selinexor PO twice weekly. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Pharmacological Study: Correlative studies

Unable to analyze data due to only 1 patient being enrolled on the study

Progression Free Survival

Objective Response Rate (Complete Response [CR] or Partial Response [PR]) by RECIST

Disease Control Rate (CR, PR, and Stable Disease)

Overall Survival

Frequency of Adverse Events Defined as Adverse Events That Are Classified as Either Not Related, Possibly, Probably, or Definitely Related to Study Treatment as Per NCI CTCAE v4.0

Fatigue

Generalized muscle weakness

Bilateral Lower Extrem Edema

Hyperglycemia

Hyponatremia

Incidence of Severe (Grade 3+) Adverse Events or Toxicities as Per NCI CTCAE v4.0

Tolerability of the Regimen Assessed Through Number of Patients Who Required Dose Modifications and/or Dose Delays

Proportion of Patients Who go Off Treatment Due to Adverse Reactions or Even Those Who Refuse Further Treatment for Lesser Toxicities That Inhibit Their Willingness to Continue Participation on the Trial

Carcinoma, Neuroendocrine

Neuroendocrine Tumors

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Adenocarcinoma

Neuroendocrine Tumor

Neuroepithelioma

Nivolumab

Temozolomide

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients receive nivolumab IV on day 1 of a 28 day cycle. Patients also receive temozolomide PO on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Dwight Owen, MD, MS

This phase II trial studies how well nivolumab and temozolomide work in treating patients with small-cell lung cancer that has come back or does not respond to treatment, or neuroendocrine cancer that has spread to other places in the body. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab and temozolomide may work better in treating patients with small-cell lung cancer and neuroendocrine cancer.

PRIMARY OBJECTIVES:

I. To evaluate the efficacy (using response rate per RECIST v1.1) of nivolumab and temozolomide for the treatment of patients with either small cell lung cancer that have progressed or recurred after prior platinum-based chemotherapy and immunotherapy (cohort 1), or progressive metastatic neuroendocrine carcinoma of any grade or primary site in any line of therapy (cohort 2).

SECONDARY OBJECTIVES:

I. To evaluate the safety profile and toxicity of combination nivolumab and temozolomide as per Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0.

II. To evaluate the progression free survival (PFS) and overall survival (OS) of patients treated with combination nivolumab and temozolomide.

III. To evaluate the central nervous system (CNS) PFS of patients with small cell lung cancer (SCLC) treated with nivolumab and temozolomide.

EXPLORATORY OBJECTIVES:

I. To determine whether treatment with nivolumab and temozolomide leads to a decrease in immune-suppressive cell populations (ie myeloid-derived suppressor cells \[MDSC\]) in peripheral blood.

II. To determine whether objective response rate (ORR), PFS, OS vary by tumor O6-methylguanine deoxyribonucleic acid (DNA) methyltransferase (MGMT) methylation at baseline.

III. To determine whether baseline tumor mutational burden is predictive of response to therapy in patients with SCLC treated with nivolumab and temozolomide.

IV. To determine whether changes in blood based mutation burden during treatment may predict clinical benefit.

V. To determine whether a composite immune and tumor cell staining score can be developed with or without PD-L1 by immunohistochemistry (IHC) to predict response in the SCLC cohort.

OUTLINE:

Patients receive nivolumab intravenously (IV) on day 1 of a 28 day cycle. Patients also receive temozolomide orally (PO) on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 8 weeks for 12 months, then every 12 weeks thereafter.

Nivolumab and Temozolomide in Treating Patients With Recurrent or Refractory Small-Cell Lung Cancer or Advanced Neuroendocrine Cancer

A Phase II, Multi-Cohort Trial of Combination Nivolumab and Temozolomide in Recurrent/Refractory Small-Cell Lung Cancer and Advanced Neuroendocrine Tumors

The study will evaluate PD-L1 by immunohistochemistry (IHC), and assess the clinical outcomes (ie OS) between patients with high expression and low expression of PD-L1.

Response will be defined by a complete response (CR) or partial response (PR), confirmed or unconfirmed. Response will be defined for patients with measurable disease and who receive at least one dose of combination treatment. Exact binomial 95% confidence intervals for the true PR+CR response rate will be calculated.

Attribution to drug, time-of-onset, duration of the event, resolution, and any concomitant medications administered will be recorded. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either ?unrelated? or ?unlikely to be related? to study treatment in the event of an actual relationship developing.

CNS PFS will be measured for patients with relapsed vs refractory small-cell lung cancer (SCLC) in cohort 1. The Kaplan-Meier method will be used.

Bristol-Myers Squibb

Dwight Owen

Immune System Diseases

Hypersensitivity

Poly(ADP-ribose) Polymerase Inhibitors

Veliparib

Patients receive veliparib PO BID on days 1-7 and temozolomide PO on days 1-5.

Patients receive placebo PO BID on days 1-7 and temozolomide as in Arm I.

Placebo

Charles Rudin

This randomized phase II trial studies how well temozolomide with or without veliparib works in treating patients with small cell lung cancer that has returned or does not respond to treatment. Temozolomide works by damaging molecules inside the cancer cells, such as deoxyribonucleic acid (DNA), that are needed for cancer survival and growth. Veliparib may stop the growth of tumor cells by blocking proteins that are needed for repairing the damaged DNA and it may also help temozolomide to kill more cancer cells. It is not yet know whether temozolomide is more effective with or without veliparib in treating patients with relapsed or refractory small cell lung cancer.

PRIMARY OBJECTIVES:

I. To demonstrate an improvement in progression free survival (PFS) at four months in patients with relapsed sensitive or refractory small cell lung cancer (SCLC) receiving ABT-888 (veliparib) and temozolomide compared to placebo and temozolomide.

SECONDARY OBJECTIVES:

I. Determine the objective response rate (ORR) (based on Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 criteria) in both arms of the study: ABT-888 and temozolomide and placebo and temozolomide.

II. Determine the overall survival (OS) of patients in both arms of the study. III. Determine the ORR, PFS and OS of ABT-888 and temozolomide and placebo and temozolomide, in the following patient groups: sensitive disease vs. refractory disease; second-line treatment vs. third-line treatment; brain metastases vs. no brain metastases.

IV. Determine the safety and tolerability of ABT-888 and temozolomide in patients with SCLC.

TERTIARY OBJECTIVES:

I. Evaluate available tumor samples for methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter by the EpiTyper assay, as well as MGMT expression by immunohistochemistry and determine if these correlate with PFS, ORR, and OS.

II. Evaluate available tumor samples for poly (ADP ribose) polymerase (PARP)-1, breast cancer 1 (BRCA-1) and RAD51 recombinase (RAD51) expression by immunohistochemistry and determine if they correlate with PFS, ORR, and OS.

III. Evaluate available tumor samples for messenger ribonucleic acid (mRNA) BRCA-1 expression and determine if it correlates PFS, ORR, and OS.

IV. Evaluate available tumor samples for phosphatase and tensin homolog (PTEN) expression by immunohistochemistry and determine if it correlates PFS, ORR, and OS.

V. Identify and enumerate circulating tumor cells (CTCs) using the Cell Search System in these patients with SCLC at baseline and at the time of repeat imaging.

VI. Correlate the number of CTCs with PFS and OS at each time point. VII. Correlate the change in CTCs with radiographic response. VIII. Correlate the number of CTCs at baseline with patient characteristics (disease burden, location of metastases, progression at existing sites or new sites of disease).

IX. Evaluate gamma H2A histone family, member X (H2AX)-positive CTCs using the CellSearch.

X. Assess the percentage increase in DNA fragments during treatment and correlate with outcome in each of the treatment groups.

XI. Evaluate plasma markers for apoptosis and angiogenesis. XII. Assess changes in plasma markers for apoptosis and angiogenesis, including caspase-cleaved cytokeratin 18 fragment (M30), soluble cytokeratin 18 (M65), pro-gastrin-releasing peptide (pro-GRP), soluble vascular endothelial growth factor (sVEGF), sVEGF receptor 2 (sVEGFR2), and soluble v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (sKIT), and correlate these markers with outcome in the two treatment arms.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive veliparib orally (PO) twice daily (BID) on days 1-7 and temozolomide PO on days 1-5.

ARM II: Patients receive placebo PO BID on days 1-7 and temozolomide as in Arm I.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 8-12 weeks.

Temozolomide With or Without Veliparib in Treating Patients With Relapsed or Refractory Small Cell Lung Cancer

A Multi-Center, Randomized, Double-Blind Phase II Study Comparing ABT-888, a PARP Inhibitor, Versus Placebo With Temozolomide in Patients With Relapsed Sensitive or Refractory Small Cell Lung Cancer

Fisher's exact test will be used to correlate response and log-rank test to correlate with progression free survival and overall survival.

Correlated with outcome in the two treatment arms.

Wilcoxon test will be used to compare the percentage increase of gammaH2AX positive cells between the two treatment groups.

Results will be expressed as binary variables. Associations with objective response, with progression free survival and with overall survival will be tested using Fisher's exact test and log-rank test, respectively.

The number of CTCs will be correlated with PFS and OS using Cox proportional hazards model. The change in CTCs will be correlated with radiographic response. The number of CTCs at baseline will be correlated with patient characteristics (disease burden, location of metastases, and progression at existing sites or new sites of disease). The number of CTC will be explored as a continuous variable and the presence of a threshold predictive of the outcome will be investigated.

Compared across the two arms using a Fisher exact test.

Corresponding exact two-sided 95% confidence intervals will be calculated and reported in both arms of the study. Comparisons between treatment arms will be performed using Fisher-exact test.

Estimated in each treatment group using Kaplan-Meier method. Group comparisons will be performed using log-rank test.

Tabulated According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0. Summary level.

Patients receive veliparib PO BID on days 1-7 and temozolomide PO on days 1-5.

Laboratory Biomarker Analysis: Correlative studies

Temozolomide: Given PO

Veliparib: Given PO

Arm I (Veliparib and Temozolomide)

Patients receive placebo PO BID on days 1-7 and temozolomide as in Arm I.

Laboratory Biomarker Analysis: Correlative studies

Placebo: Given PO

Temozolomide: Given PO

Arm II (Placebo and Temozolomide)

Dr. Charles Rudin

The study will be performed as a double-blind, placebo controlled, randomized Phase II in patients with relapsed sensitive or refractory SCLC. Eligible patients will be randomized 1:1 to one of two treatment arms: ABT-888 and temozolomide as the investigational arm, versus placebo and temozolomide as the control arm. The randomization will be stratified by center and by type or relapse (sensitive vs. refractory). The primary objective is to compare the two treatment regimens with respect to efficacy, expressed as Progression Free Survival (PFS) at 4 months post-randomization. PFS will be calculated as proportion of patients alive and without evidence of disease at 4 months after randomization.

Progression-free Survival, Calculated as the Proportion of Patients Alive and Without Evidence of Disease

Overall Response (ORR) by RECIST 1.1 Criteria

Number of Participants With Adverse Events

BRCA1 Expression, Assessed by Immunohistochemistry

Changes in Plasma Markers

GammaH2AX Levels

MGMT Expression, Assessed by Immunohistochemistry

Number of Circulating Tumor Cells

PARP-1 Expression

Presence of MGMT Promoter Methylation, Assessed by the EpiTyper Assay

PTEN Expression, Assessed by Immunohistochemistry

RAD51 Expression, Assessed by Immunohistochemistry

Antibodies

Antibodies, Monoclonal

Durvalumab

Immunoglobulins

Tremelimumab

Ipilimumab

Patients receive tremelimumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive durvalumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients achieving disease control may restart treatment upon evidence of progressive disease, with or without confirmation.

Patients undergo stereotactic body radiation therapy (SBRT) or hypofractionated radiation therapy daily for 5 days over 1 week or for 3 fractions every other day for 1 week and then receive the same treatment as in Arm I.

Undergo hypofractionated radiation therapy

Hypofractionated Radiation Therapy

Stereotactic Body Radiation Therapy

Taofeek Owonikoko, MD, PhD

This randomized clinical trial studies how well tremelimumab and durvalumab with or without radiation therapy works in treating patients with small cell lung cancer that has returned after a period of improvement. Monoclonal antibodies, such as tremelimumab and durvalumab, may limit the ability of tumor cells to grow and spread by enhancing immune function. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving tremelimumab and durvalumab together with radiation therapy may lead to improved clinical benefit.

PRIMARY OBJECTIVE:

I. To assess the efficacy (progression free survival \[PFS\] and objective response rate \[ORR\]) of combined immune checkpoint inhibitor therapy as treatment for relapsed small-cell lung cancer (SCLC).

SECONDARY OBJECTIVES:

I. To assess the impact of antigen priming using radiation therapy (XRT) on the efficacy of immune checkpoint inhibitors.

II. To determine immune related objective response rate.

III. To estimate overall survival measured as time from randomization to death from any cause.

TERTIARY OBJECTIVES:

I. To characterize tumor infiltrating lymphocytes (TILs) and programmed cell death 1 ligand 1 (PD-L1)/programmed cell death 1 (PD1) expression in paired tumor biopsies at baseline, end of cycle 2 and at the time of progression.

II. To determine dynamic changes in cell free deoxyribonucleic acid (DNA) (cfDNA) and the immunophenotype of peripheral blood repertoire of circulating lymphocytes using multiparameter flow cytometry.

III. To determine changes in circulating cytokine mediators of inflammation and immunity using Luminex assay.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive tremelimumab intravenously (IV) over 1 hour on day 1. Treatment repeats every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive durvalumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients achieving disease control may restart treatment upon evidence of progressive disease, with or without confirmation.

ARM II: Patients undergo radiation therapy daily for 5 days over 1 week or for 3 fractions every other day for 1 week and then receive the same treatment as in Arm I.

After completion of study treatment, patients are followed up periodically.

Tremelimumab and Durvalumab With or Without Radiation Therapy in Patients With Relapsed Small Cell Lung Cancer

A Randomized Study of Tremelimumab Plus Durvalumab Combination With or Without Radiation in Relapsed Small Cell Lung Cancer

Change in circulating and tumor-infiltrating lymphocytes between baseline and on-treatment samples at the end of Cycle 1. The proportion was calculated as the number of specific lymphocytes subset out of the total number of lymphocytes at baseline compared to the same proportion at the end of cycle 1.

Time from initiation of therapy to objective disease progress or death

Disease response to therapy measured according to RECIST 1.1 criteria

Disease response to treatment using immune-related response rate (irRR) criteria

Time interval from entering the study until death

AstraZeneca

Emory University

Patients receive tremelimumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive durvalumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients achieving disease control may restart treatment upon evidence of progressive disease, with or without confirmation.

Durvalumab: Given IV

Tremelimumab: Given IV

Arm I (Tremelimumab, Durvalumab)

Patients undergo stereotactic body radiation therapy (SBRT) or hypofractionated radiation therapy daily for 5 days over 1 week or for 3 fractions every other day for 1 week and then receive the same treatment as in Arm I.

Durvalumab: Given IV

Hypofractionated Radiation Therapy: Undergo hypofractionated radiation therapy

Stereotactic Body Radiation Therapy: Undergo SBRT

Tremelimumab: Given IV

Arm II (RT, Tremelimumab, Durvalumab)

The measure of dispersion data are not available. All efforts were made to obtain these data from the PI and the study documentation.

Dr. Taofeek Owonikoko

Progression Free Survival (PFS)

Objective Response Rate

Immune-related Objective Response Rate

Durvalumab: Given IV

Tremelimumab: Given IV

Patients in Arm II undergo stereotactic body radiation therapy (SBRT) or hypofractionated radiation therapy daily for 5 days over 1 week or for 3 fractions every other day for 1 week and then receive the same treatment as in Arm I.

Pooled Analysis (Arms I and II)

All patients with at least 2 paired samples collected at baseline and on-treatment at end of cycle 1

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pegylated Irinotecan NKTR 102 in Treating Patients With Relapsed Small Cell Lung Cancer	NCT01876446	Recurrent Small...	Laboratory Biom... Pegylated Irino... Pharmacological...	18 Years -	Roswell Park Cancer Institute
Selinexor in Treating Patients With Relapsed Small Cell Lung Cancer	NCT02351505	Recurrent Small...	Selinexor Laboratory Biom... Pharmacological...	18 Years -	Ohio State University Comprehensive Cancer Center
Nivolumab and Temozolomide in Treating Patients With Recurrent or Refractory Small-Cell Lung Cancer or Advanced Neuroendocrine Cancer	NCT03728361	Grade I Neuroen... Grade II Neuroe... Grade III Neuro... Metastatic Neur... Neuroendocrine ... Recurrent Small... Refractory Smal... Lung Cancer Sta... Large Cell Neur... Neuroendocrine ... Small Cell Lung... Small-cell Lung...	Nivolumab Temozolomide	18 Years -	Ohio State University Comprehensive Cancer Center
Temozolomide With or Without Veliparib in Treating Patients With Relapsed or Refractory Small Cell Lung Cancer	NCT01638546	Recurrent Small...	Laboratory Biom... Placebo Temozolomide Veliparib	18 Years -	National Cancer Institute (NCI)
Temozolomide With or Without Veliparib in Treating Patients With Relapsed or Refractory Small Cell Lung Cancer	NCT01638546	Recurrent Small...	Laboratory Biom... Placebo Temozolomide Veliparib	18 Years -	National Cancer Institute (NCI)
Tremelimumab and Durvalumab With or Without Radiation Therapy in Patients With Relapsed Small Cell Lung Cancer	NCT02701400	Recurrent Small...	Durvalumab Hypofractionate... Stereotactic Bo... Tremelimumab	18 Years -	Emory University
Linsitinib or Topotecan Hydrochloride in Treating Patients With Relapsed Small Cell Lung Cancer	NCT01533181	Recurrent Small...	Laboratory Biom... Linsitinib Pharmacological... Topotecan Hydro...	18 Years -	National Cancer Institute (NCI)
Topotecan Hydrochloride and Doxorubicin Hydrochloride in Treating Relapsed or Refractory Small Cell Lung Cancer	NCT00856037	Recurrent Small...	Doxorubicin Hyd... Laboratory Biom... Quality-of-Life... Topotecan Hydro...	19 Years -	University of Nebraska
A Randomized Phase II Study of Cisplatin and Etoposide in Combination With Either Hedgehog Inhibitor GDC-0449 or IGF-1R MOAB IMC-A12 for Patients With Extensive Stage	NCT00887159	Extensive Stage... Recurrent Small...	Cisplatin Cixutumumab Etoposide Laboratory Biom... Vismodegib	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for recurrent small cell lung carcinoma