Neoplasms

All Conditions

Rare Diseases

Sarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Patients undergo intense follow-up every 3 months for 2 years consisting of restaging with CT-chest and imaging of the primary site.

Patients undergo limited follow-up every 6 months for 2 years consisting of restaging with either CT-chest or CXR and imaging of the primary site.

Patients undergo intense follow-up every 3 months for 2 years as in Group 1, Arm I.

Chest Radiography

Computed Tomography

Follow-Up

Imaging Technique

Questionnaire Administration

Christina L Roland, MD

Christina L. Roland

This phase II trial studies how anxiety is affected by 2 types of follow-up after surgery, limited follow-up and intense follow-up, in patients with stage II-III soft tissue sarcoma of the trunk and extremities. In cancer survivors, the fear of cancer coming back (recurring) is common and may persist long after the end of treatment. It may also be exacerbated by return visits for imaging (surveillance). The purpose of this study is to determine how patients' anxiety and other cancer-related outcomes are affected by how often surveillance is done.

PRIMARY OBJECTIVE:

I. To evaluate whether a risk-based limited follow-up surveillance is associated with reduced patient anxiety compared to risk-based intense surveillance.

SECONDARY OBJECTIVE:

I. To evaluate the impact of reduced surveillance in low-risk patients on overall survival, time to local or distant recurrence, anxiety at early and late time-points, out of pocket costs, and number of missed or extra clinic visits, compared to the risk-based intense follow-up in both low-risk and high-risk patients.

OUTLINE: Patients are assigned to 1 of 2 groups based on risk status.

GROUP 1 (LOW RISK): Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo intense follow-up every 3 months for 2 years consisting of restaging with computed tomography (CT)-chest and imaging of the primary site.

ARM II: Patients undergo limited follow-up every 6 months for 2 years consisting of restaging with either CT-chest or chest x-ray (CXR) and imaging of the primary site.

GROUP 2 (HIGH RISK): Patients undergo intense follow-up every 3 months for 2 years as in Group 1, Arm I.

Evaluating the Impact of Limited Compared With Intense Post-Operative Surveillance on Patient-Reported Outcomes in Patients With Stage II-III Soft Tissue Sarcoma of the Trunk and Extremities

Evaluating the Impact of Limited vs. Intense Post-Operative Surveillance on Patient-Reported Outcomes in Patients With Soft Tissue Sarcoma

Will be calculated as the area under the curve by obtaining patient-reported outcomes at 4 separate time points and then graphically calculating and comparing the area under the curve for each patient. The mean area under the curve of the Fear of Cancer Recurrence Inventory - Short Form will be estimated along with a 95% confidence interval within each study group.

Will be estimated along with a 95% confidence interval within each study group.

Will be assessed by the Fear of Cancer Recurrence Inventory - Short Form via linear mixed models over time and to compare changes of these assessments over time between the two low-risk groups adjusting for important covariates such age, gender and other patient prognostic factors.

Will be assessed by the Impact of Events scale via linear mixed models over time and to compare changes of these assessments over time between the two low-risk groups adjusting for important covariates such age, gender and other patient prognostic factors.

Will be assessed by the Hospital Anxiety and Depression Scale via linear mixed models over time and to compare changes of these assessments over time between the two low-risk groups adjusting for important covariates such age, gender and other patient prognostic factors.

Will be assessed by the Cost Survey via linear mixed models over time and to compare changes of these assessments over time between the two low-risk groups adjusting for important covariates such age, gender and other patient prognostic factors.

Will be estimated using the Kaplan-Meier method. Log-rank test will be performed to test the difference in survival between groups.

The analysis of number of missed or extra clinic visits will be descriptive in nature.

M.D. Anderson Cancer Center

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Digestive System Diseases

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Adenocarcinoma

Cystadenocarcinoma, Serous

Fallopian Tube Neoplasms

Peritoneal Neoplasms

Cystadenocarcinoma

Neoplasms, Glandular and Epithelial

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

Fallopian Tube Diseases

Abdominal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Peritoneal Diseases

Neoplasms, Cystic, Mucinous, and Serous

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Adenocarcinoma of the Appendix

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Carboplatin

Letrozole

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Cycles repeat every 21 days for up to 6 cycles. Patients then receive letrozole PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo blood collection and tumor biopsy during screening as well as medical imaging throughout the study.

Patients receive letrozole PO QD. Cycles repeat every 21 days for up to 6 cycles. Patients then receive letrozole orally PO QD in the absence of disease progression or unacceptable toxicity as maintenance therapy. Patients undergo blood collection and tumor biopsy during screening as well as medical imaging throughout the study.

Biopsy

Biospecimen Collection

Site Public Contact

Nitya Alluri

Nicholas DiBella

John H. Farley

John A. Ellerton

Shahzad Siddique

Setsuko K. Chambers

Jay W. Carlson

David B. Engle

Heather R. Williams

Ramey D. Littell

Deepti Behl

Mihae Song

Yevgeniya J. Ioffe

Lee-May Chen

Amanda N Fader

This phase III trial studies how well letrozole with or without paclitaxel and carboplatin works in treating patients with stage II-IV low-grade serous carcinoma of the ovary, fallopian tube, or peritoneum. Letrozole is an enzyme inhibitor that lowers the amount of estrogen made by the body which in turn may stop the growth of tumor cells that need estrogen to grow. Drugs used in chemotherapy, such as paclitaxel and carboplatin, 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. It is not yet known whether giving letrozole alone or in combination with paclitaxel and carboplatin works better in treating patients with low-grade serous carcinoma of the ovary, fallopian tube, or peritoneum compared to paclitaxel and carboplatin without letrozole.

PRIMARY OBJECTIVE:

I. To examine if letrozole monotherapy/maintenance (L/L) is non-inferior to intravenous (IV) paclitaxel/carboplatin and maintenance letrozole (CT/L) with respect to progression-free survival (PFS) in women with stage II-IV primary low-grade serous carcinoma of the ovary or peritoneum after primary surgical cytoreduction.

SECONDARY OBJECTIVES:

I. To compare the nature, frequency and maximum degree of toxicity as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 for each treatment arm.

II. To compare the relative frequency of objective tumor response in those with measurable disease after cytoreductive surgery for each treatment arm.

III. To compare overall survival for each treatment arm. IV. To compare the CT/L and L/L arms with respect to patients' adherence to letrozole therapy as measured by pill counts.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Cycles repeat every 21 days for up to 6 cycles. Patients then receive letrozole orally (PO) once daily (QD) in the absence of disease progression or unacceptable toxicity. Patients undergo blood collection and tumor biopsy during screening as well as medical imaging throughout the study.

ARM II: Patients receive letrozole PO QD. Cycles repeat every 21 days for up to 6 cycles. Patients then receive letrozole orally PO QD in the absence of disease progression or unacceptable toxicity as maintenance therapy. Patients undergo blood collection and tumor biopsy during screening as well as medical imaging throughout the study.

After completion of study treatment/intervention, patients/participants are followed up every 3 months for 1 year, then every 6 months for 3 years, then annually thereafter.

Letrozole With or Without Paclitaxel and Carboplatin in Treating Patients With Stage II-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

A Randomized Phase III, Two-Arm Trial of Paclitaxel/Carboplatin/Maintenance Letrozole Versus Letrozole Monotherapy in Patients With Stage II-IV, Primary Low-Grade Serous Carcinoma of the Ovary or Peritoneum

The PFS comparison will be assessed at the second interim and final analyses using a logrank test stratified by country and residual disease status. Estimates for the letrozole/letrozole (L/L) vs paclitaxel/carboplatin/letrozole (CT/L) hazard ratio and its confidence interval will be obtained using a stratified Cox proportional hazards model. Potential confounding factors, including the stratification factors, performance status and self-declared racial designation will be considered in a final exploratory model. A forest plot of treatment hazard ratios with confidence intervals within subgroups will also be reported. PFS will be characterized by treatment group with Kaplan-Meier plots and estimates of the median PFS.

The nature, frequency and degree of toxicity will be tabulated at the System Organ Class and AE Term levels using Common Terminology Criteria for Adverse Events version 5.0. Each patient will be represented according the maximum grade observed for each term, within randomized treatment assignment. Tabulations will show the number and percentage of patients by maximum grade, within their randomized treatment assignment.

Will be estimated as the binomial proportion of patients with best overall response of complete response (CR) or partial response (PR) among patients with measurable disease after cytoreductive surgery. Response rates and their 95% Wilson-Score confidence intervals will be estimated for each treatment arm, using the randomized treatment assignment. The odds-ratio for ORR in the L/L vs CT/L arms will be estimated from the multivariable logistic regression model adjusted for stratification factors.

Will be defined among patients with best overall response of CR or PR. Comparison of response duration between the randomized treatment arms will be supported by Kaplan Meier methods, and the corresponding estimates for median duration and its 95% confidence intervals.

Differences in OS across the randomized treatment groups will be assessed using Kaplan Meier methods, with median time to death estimates and the corresponding 95% confidence intervals. The L/L vs CT/L hazard ratio will be estimated by a proportional hazards model stratified by the randomization stratification factors.

Will be quantified as the mean rate of adherence (MRA), calculated as the proportion of product not returned divided by the number of days since the previous visit at which study products were dispensed. Currently, the letrozole is delivered in a 2.5 mg pill, and the recommended dose is 2.5 mg per day. This outcome will be computed for each treatment cycle (generally 21 days). The mean MRA will be compared between the randomized treatment groups using linear mixed model methods. The model will be specified with a random patient effect, and fixed effects for randomized treatment indicator, time (cycle number) and the interaction, with an adjustment for the protocol stratification factors. Primary interest is in the difference in mean (MRA) at cycles 1, 6 and 12 between the treatment group. The results will be reported as the estimated mean (MRA) and 95% confidence intervals for each treatment/time combination. Treatment differences within stratification factors may also be considered.

National Cancer Institute (NCI)

NRG Oncology

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Recurrence

Osteosarcoma

Neuroblastoma

Disease Attributes

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Gaucher Disease Type 2

Neuroepithelioma

Antirheumatic Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Vaccines

Immunologic Factors

Immunosuppressive Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Antimetabolites

LYMPHODEPLETION CHEMOTHERAPY: Patients receive fludarabine phosphate IV daily on days -5 to -2 and cyclophosphamide IV daily on days -4 to -2.

GD2CART: Patients receive GD2CART cells IV on day 0.

Patients also undergo ECHO, MUGA or cardiac MRI scan during screening, blood sample collection throughout the trial, and tumor biopsies as clinically indicated. In addition, patients undergo standard imaging scans throughout the trial.

Echocardiography

Fludarabine Phosphate

GD2-CAR-expressing Autologous T-lymphocytes

Magnetic Resonance Imaging of the Heart

Multigated Acquisition Scan

Rosandra N Kaplan

This phase I trial investigates the side effects and determines the best dose of an immune cell therapy called GD2CART, as well as how well it works in treating patients with osteosarcoma or neuroblastoma that has come back (relapsed) or does not respond to treatment (refractory). T cells are infection fighting blood cells that can kill tumor cells. The T cells given in this trial will come from the patient and will have a new gene put in them that makes them able to recognize GD2, a protein on the surface of tumor cells. These GD2-specific T cells may help the body's immune system identify and kill GD2 positive tumor cells.

PRIMARY OBJECTIVES:

I. Determine the feasibility of producing T cells modified to express a GD2-specific chimeric antigen receptor (GD2-CAR-expressing autologous T-lymphocytes \[GD2CART\]) meeting established release criteria using a dasatinib containing culture platform and retroviral vector in the Miltenyi CliniMACS Prodigy (Registered Trademark) system.

II. Determine the safety and maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) via administration of escalating doses of autologous GD2CART in children and young adults with relapsed/refractory osteosarcoma and neuroblastoma following cyclophosphamide-fludarabine based lymphodepletion.

III. Determine clinical activity in a preliminary fashion of autologous GD2CART in children and young adults with relapsed, refractory osteosarcoma and neuroblastoma.

SECONDARY OBJECTIVES:

I. Measure persistence of adoptively transferred GD2CART and correlate this with antitumor effects.

II. If unacceptable toxicity occurs that is possibly, probably, or likely related to GD2CART, assess the capacity for rimiducid (AP1903), a dimerizing agent, to mediate clearance of the genetically engineered cells and resolve toxicity.

III. Describe the feasibility and tolerability of a second infusion of GD2CART in select patients.

EXPLORATORY OBJECTIVES:

I. Compare persistence of GD2CART administered in this trial to that observed in a previous trial using GD2.OX40.28.z.iCasp9 CAR T cells (NCI 14-C-0059) and assess features of the T cell product and the expanded T cells in vivo that correlate with persistence.

II. Conduct exploratory studies measuring levels of circulating myeloid cells including myeloid derived suppressor cells (MDSCs) in patients treated on this trial and compare levels to those observed in NCI 14-C-0059.

III. Explore GD2 expression in patients with neuroblastoma and osteosarcoma, including patients who have previously received anti-GD2 antibodies, from tissue and/or bone marrow samples at study entry and if available, after cell infusion.

OUTLINE: This is a dose-escalation study of GD2CART followed by a dose-expansion study.

LYMPHODEPLETION CHEMOTHERAPY: Patients receive fludarabine phosphate intravenously (IV) daily on days -5 to -2 and cyclophosphamide IV daily on days -4 to -2.

GD2CART: Patients receive GD2CART cells IV on day 0.

Patients also undergo echocardiogram (ECHO), multigated acquisition scan (MUGA) or cardiac magnetic resonance imaging (MRI) scan during screening, blood sample collection throughout the trial, and tumor biopsies as clinically indicated. In addition, patients undergo standard imaging scans throughout the trial.

After completion of study treatment, patients are followed up three times weekly until day 14, twice weekly until day 28, at months 2, 3, 6, 9, and 12, every 3 months until the end of the second year, then annually for up to 10 years.

Testing a New Immune Cell Therapy, GD2-Targeted Modified T-cells (GD2CART), in Children, Adolescents, and Young Adults With Relapsed/Refractory Osteosarcoma and Neuroblastoma, The GD2-CAR PERSIST Trial

GD2-CAR PERSIST: Production and Engineering of GD2-Targeted, Receptor Modified T Cells (GD2CART) for Osteosarcoma or Neuroblastoma to Increase Systemic Tumor Exposure

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Associations between biomarkers and chimeric antigen receptor (CAR) persistence will be assessed by regression. The exact statistical model will depend on the observed responses which might not be linearly related to biomarkers but could show logistic or other association. Relationships of biomarkers to outcomes (overall survival, progression free survival) will be assessed by Cox regression using baseline measurements as predictors. The proportional hazards assumption will be checked retrospectively.

Will measure levels of circulating myeloid cells including myeloid derived suppressor cells (MDSCs) in patients treated on this trial and compare levels to those observed in NCI 14-C-0059.

Tumor and/or normal tissue will be obtained from archival sample, tissue or tumor biopsy, or any clinically indicated surgeries. Bone marrow aspirations will be conducted in all patients with neuroblastoma. In patients with osteosarcoma, bone marrow aspirations will be conducted only if clinically indicated, i.e. known bone marrow involvement.

Success will be defined by manufacturing and expansion of GD2CART to satisfy the targeted dose level and meet the requirements of the Certificate of Analysis. Specifically, dose escalation will proceed if 3 or more of the first 3 to 6 patients in a dose level are able to produce adequate cells for evaluation.

Safety of GD2CART will be by the incidence and severity of dose limiting toxicities (DLTs), treatment emergent AEs (TEAEs), serious adverse events (SAEs), laboratory abnormalities, changes in vital signs, and changes in physical examination following infusion of GD2CART cells.

Simon's two stage design will be used to evaluate the clinical benefit of GD2CART after conditioning lymphodepletion chemotherapy in two groups of patients: children and young adults with recurrent, refractory osteosarcoma and neuroblastoma.

Persistence of GD2CART and correlation with tumor regression and sustained clinical benefit will be assessed. Persistence will be defined as the duration of time that GD2CART cells can be detected above the background rate (baseline measure) as measured by polymerase chain reaction (PCR). The persistence will be compared between the different response statuses (responders versus non-responders) using a t-test allowing for unequal variance.

The toxicity is defined to be reversed or resolved when the toxicity grading has resolved to grade 2 or below. The resolution of toxicity will be summarized descriptively.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Evaluating the Impact of Limited Compared With Intense Post-Operative Surveillance on Patient-Reported Outcomes in Patients With Stage II-III Soft Tissue Sarcoma of the Trunk and Extremities	NCT04751409	Stage II Soft T... Stage III Soft ... Stage IIIA Soft... Stage IIIB Soft...	Chest Radiograp... Computed Tomogr... Follow-Up Follow-Up Imaging Techniq... Questionnaire A...	18 Years -	M.D. Anderson Cancer Center
Letrozole With or Without Paclitaxel and Carboplatin in Treating Patients With Stage II-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer	NCT04095364	Low Grade Fallo... Ovarian Low Gra... Primary Periton... Stage II Fallop... Stage II Ovaria... Stage II Primar... Stage III Fallo... Stage III Ovari... Stage III Prima... Stage IV Fallop... Stage IV Ovaria... Stage IV Primar...	Biopsy Biospecimen Col... Carboplatin Imaging Techniq... Letrozole Paclitaxel	18 Years -	NRG Oncology
Testing a New Immune Cell Therapy, GD2-Targeted Modified T-cells (GD2CART), in Children, Adolescents, and Young Adults With Relapsed/Refractory Osteosarcoma and Neuroblastoma, The GD2-CAR PERSIST Trial	NCT04539366	Recurrent Neuro... Recurrent Osteo... Refractory Neur... Refractory Oste...	Biopsy Biospecimen Col... Cyclophosphamid... Echocardiograph... Fludarabine Pho... GD2-CAR-express... Imaging Techniq... Magnetic Resona... Multigated Acqu...	- 40 Years	National Cancer Institute (NCI)

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