Neoplasms

All Conditions

Nervous System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

Diseases and Abnormalities at or Before Birth

Musculoskeletal Diseases

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Rare Diseases

Carcinoma

Glioma

Meningioma

Osteosarcoma

Neuroblastoma

Sarcoma

Carcinoma, Renal Cell

Liver Neoplasms

Wilms Tumor

Medulloblastoma

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

Ependymoma

Craniopharyngioma

Adamantinoma

Rhabdomyosarcoma

Rhabdoid Tumor

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Sarcoma, Clear Cell

Neoplasms, Neuroepithelial

Choroid Plexus Neoplasms

Ameloblastoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Myosarcoma

Neoplasms, Vascular Tissue

Meningeal Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Syndrome

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

Bone Neoplasms

Bone Diseases

Cerebral Ventricle Neoplasms

Brain Neoplasms

Brain Diseases

Central Nervous System Diseases

Renal Cell Carcinoma

Soft Tissue Sarcoma

Clear Cell Renal Cell Carcinoma

Germ Cells Tumors

Wilms' Tumor

Ewing Sarcoma

Neuroepithelioma

Dysembryoplastic Neuroepithelial Tumor

A total of 200 neuroblastoma, brain tumor, and rare tumor patients will be treated. Guided therapy will allow the use of any therapeutic combination (up to 4 agents) provided it includes medications contained in the study report. All patients will be followed for survival, disease response, progression and safety. All patients will be treated according to the discretion of the treating oncologist and study committee (minimum 3 oncologists and one pharmacist). Extent of disease will be measured and assessed for changes throughout the course of the study and at 6-8 week intervals (every 2 cycles).

Guided Therapy

Giselle Sholler, MD

The purpose of this study is to test the feasibility (ability to be done) of experimental technologies to determine a tumor's molecular makeup. This technology includes a genomic report based on DNA exomes and RNA sequencing that will be used to discover new ways to understand cancers and potentially predict the best treatments for patients with cancer in the future.

Molecular-Guided Therapy for Childhood Cancer

Molecular-guided Therapy for the Treatment of Patients With Relapsed and Refractory Childhood Cancers

The definition of feasibility is: Enrollment onto study, genomic profile, analysis and report generation completed, tumor board held with treatment decision, treatment review completed, start of treatment, and completion of 1 cycle of therapy.

To determine the safety of allowing a molecular tumor board to determine individualized treatment plans

To determine the activity of treatments chosen based on Overall response rate (ORR) using RESIST criteria. The assessment of response will include the initial measurable targets and will be performed after cycle 2, then after every other cycle. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI imaging and/or by MIBG or PET scans: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease, At least a 20% increase in the sum of the disease measurements for measurable lesions, Stable Disease, Neither sufficient decrease to qualify for PR or sufficient increase to qualify for PD from study entry. Overall Response (OR) = CR + PR.

Time to progression (PFS), defined as the period from the start of the treatment until the criteria for progression are met taking as reference the screening measurements. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of the disease measurements for measurable lesions, taking as reference the smallest disease measurement recorded since the start of treatment (nadir), and minimum 5 mm increase over the nadir or the appearance of one or more new lesions or appearance of positive bone marrow.

Translational Genomics Research Institute

Dell, Inc.

Giselle Sholler

Study Chair

A total of 200 neuroblastoma, brain tumor, and rare tumor patients will be treated. Guided therapy will allow the use of any therapeutic combination (up to 4 agents) provided it includes medications contained in the study report. All patients will be followed for survival, disease response, progression and safety. All patients will be treated according to the discretion of the treating oncologist and study committee (minimum 3 oncologists and one pharmacist). Extent of disease will be measured and assessed for changes throughout the course of the study and at 6-8 week intervals (every 2 cycles).

Guided Therapy: A total of 200 neuroblastoma, brain tumor, and rare tumor patients will be treated. Guided therapy will allow the use of any therapeutic combination (up to 4 agents) provided it includes medications contained in the study report. All patients will be followed for survival, disease response, progression and safety. All patients will be treated according to the discretion of the treating oncologist and study committee (minimum 3 oncologists and one pharmacist). Extent of disease will be measured and assessed for changes throughout the course of the study and at 6-8 week intervals (every 2 cycles).

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Tumor Type

Subjects that started at least one dose of study therapy

Subjects on study with a diagnosis of Neuroblastoma

Subjects on study with a diagnosis of a CNS Tumor which included, but was not limited to, Ependymoma, Glioblastoma, Diffuse Midline Glioma, and Other CNS Tumors.

CNS Tumors

Subjects on study with a diagnosis of a rare solid tumor which included, but was not limited to, Rhabdomyosarcoma, Ewing Sarcoma, Osteosarcoma, and Other Rare Tumors.

Rare Tumors

Days to Treatment Will be Used in Order to Determine Feasibility of Using Tumor Samples to Assess Genomic Sequencing Using Predictive Modeling to Make Real-time Treatment Decisions for Children With Relapsed/Refractory Cancers.

All subjects that received at least one dose of study therapy.

Number of Participants With an Unexpected Adverse Events as a Measure of Safety

Complete Response

No Evidence of Disease

Partial Response

Stable Disease

Progressive Disease

Having at least one disease evaluation following completion of at least one cycle of molecular-guided therapy

Overall Response Rate (ORR) of Participants by the Presence of Radiologically Assessable Disease by Cross-sectional CT or MRI Imaging and/or by MIBG or PET Scans.

Time on study was measured in days from the date of initial biopsy to date of last administration of study therapy. For subjects with \>1 biopsies and \>1 MGT regimens, the off-therapy date from their last treatment was used.

Progression Free Survival (PFS) Interval Will be Measured by Days and Compared to the PFS of Previous Chemotherapy Regimens Since Relapse for Each Patient.

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Immune System Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Hypersensitivity

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Vinorelbine

Pemetrexed

Cisplatin

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Tubulin Modulators

Antimitotic Agents

Folinic Acid

Folate

Vitamin B9

Resected tumor was used for genomic expression profiling. Patients with a genomic expression pattern suggestive of vinorelbine sensitivity were given cisplatin + vinorelbine.

Resected tumor was used for genomic expression profiling. Patients with a genomic expression pattern suggestive of pemetrexed sensitivity were given cisplatin + pemetrexed.

Vinorelbine 25 mg/m2 IV over 6-10 minutes on days 1 and 8, followed by Cisplatin 75 mg/m2 IV over 60 minutes on day 1 (every 21 days x 4 cycles).

Vinorelbine followed by Cisplatin

Pemetrexed 500 mg/m2 IV infusion over approximately 10 minutes on day 1, followed by Cisplatin 75 mg/m2 IV over 60 min on day 1 (every 21 days x 4 cycles)

Pemetrexed followed by Cisplatin

Neal Ready, Ph.D., M.D.

This study assigned subjects to either cisplatin/vinorelbine or cisplatin/pemetrexed chemotherapy using a genomic based expression profile to determine chemotherapy sensitivity in completely resected early stage non-squamous non-small-cell lung cancer (NSCLC). The vinorelbine-sensitive tumors group received Vinorelbine followed by cisplatin, while the pemetrexed-sensitive tumors group received pemetrexed followed by cisplatin. The primary objective of this trial was to determine whether genomic-based adjuvant chemotherapy treatment increased the 2-year progression-free survival rate in completely resected patients with NSCLC compared to historic controls. Secondary objectives included: 1) estimation of the percentage of completely resected NSCLC tumors that can be adequately analyzed and used to direct specific adjuvant chemotherapy; 2) estimation of the proportion of patients who are assigned to treatment with vinorelbine and pemetrexed; 3) evaluation of drug sensitivity patterns of cisplatin and pemetrexed in both treatment arms; 4) description of the overall median survival experience of treated patients; and 5) assessment of patient understanding and perceptions of participating in a clinical trial evaluating cancer genomics for adjuvant treatment of early stage lung cancer.

The proposed study is a multi-center open label phase II study of the chemotherapy doublets cisplatin/vinorelbine and cisplatin/pemetrexed as adjuvant therapy in early stage non-squamous NSCLC.

Eligible patients had no previous treatment for the current diagnosis of NSCLC. The two treatment groups of patients will be determined by gene expression profile analysis of each patient's tumor: one group of vinorelbine-sensitive patients and one group of pemetrexed-sensitive patients. The genomic expression profiling that was utilized generated a percentage for likelihood of chemotherapy sensitivity. Patients were directed to receive the chemotherapy regimen for which the percentage of predicted sensitivity is highest. For instance, if the model predicted the likelihood of tumor sensitivity was 46% to vinorelbine and 48% to pemetrexed, then the adjuvant chemotherapy would be directed to cisplatin/pemetrexed. Patients whose tumors could not be adequately analyzed for gene expression were offered adjuvant therapy off protocol as deemed appropriate by their primary oncologist. Patients with either squamous or non-squamous cell histology were eligible to participate in this study as indicated in study protocols dated prior to January 25, 2010. An amendment to the protocol on January 25, 2010 indicated inclusion of only non-squamous histology. However, because of low accrual after January 25, 2010 (5 patients, including 2 screen failures), this report reflects the original study outcomes that includes both squamous and non-squamous histologies.

Thirty-one patients with stage IB (\> 4 cm), II or IIIA non-squamous NSCLC were enrolled, from which 24 were assigned treatment. The vinorelbine-sensitive tumors group received Vinorelbine 25 mg/m2 days 1 and 8, followed by cisplatin 75 mg/m2 day 1, every 21 days for 4 cycles. The pemetrexed-sensitive tumors group received pemetrexed 500 mg/m2 day 1 followed by cisplatin 75 mg/m2 day 1, every 21 days for 4 cycles. Standard pre-medication regimens included dexamethasone, vitamin B12 and folate supplementation in the pemetrexed group. Patients in both groups will receive up to a maximum of 4 cycles of therapy.

Subsequent reevaluation of the genomic signatures of chemotherapy sensitivity have shown that they were irreproducible, suggesting inaccurate patient assignments into the two treatment arms. As a result, it would be inappropriate to separately analyze outcomes for the different treatment groups. Instead, information from both arms will be combined to reflect the overall measure of two-year progression-free survival in this study. Similarly for secondary objectives, both arms will be combined to address endpoints.

To assess patient understanding and perceptions of participating in a clinical trial evaluating cancer genomics for adjuvant treatment of early stage lung cancer, patients provided responses for the following questions at baseline:

1. Did your doctor talk to you today about choosing chemotherapy treatment for lung cancer based on the genomics of your tumor?
2. How well did you understand what you doctor told you about choosing chemotherapy based on the genomics of your tumor? (circle a number between 1 and 7, where 1 = very poorly and 7 = very well)
3. Do you think the type of chemotherapy that you will get is based on the genomics of your tumor?
4. Do you think you will get better medical care for the treatment of your lung cancer if it is based on the genomics of your tumor?
5. To what extent do you think treating lung cancer based on the genomics of the tumor will lead to more successful treatment strategies? (circle a number between 1 and 7, where 1 = definitely will not lead to a more successful treatment and 7 = definitely will lead to a more successful treatment)
6. How effective do you think chemotherapy will be at stopping your cancer from coming back? (circle a number between 1 and 7, where 1 = not at all effective and 7 = completely effective)
7. To what extent is YOUR lung cancer primarily caused by genetics? (circle a number between 1 and 7, where 1 = not at all caused by genetics and 7 = completely caused by genetics)
8. To what extent to do you think your lung cancer is treatable? (circle a number between 1 and 7, where 1 = definitely not treatable and 7 = definitely treatable)
9. Did your doctor talk to you about your chance of your lung cancer coming back? (Yes - go to question 10, No - go to question 11, Do not know - go to question 11)
10. What did your doctor say was your chance of your cancer coming back? (Low Risk, Moderate or intermediate risk, High risk, Do not know)
11. What do you think is your chance of your lung cancer coming back in the next year on a scale from 1 to 7 where 1=definitely will not come back and 7=definitely will come back?
12. How worried are you that your lung cancer will come back in the next year? (circle a number between 1 and 7, where 1=not at all worried and 7=extremely worried)

Adjuvant Cisplatin With Either Genomic-Guided Vinorelbine or Pemetrexed for Early Stage Non-Small-Cell Lung Cancer

Phase II Prospective Study Evaluating the Role of Directed Cisplatin Based Chemo With Either Vinorelbine or Pemetrexed for the Adj Tx of Early Stage NSCLC in Patients Using Genomic Expression Profiles of Chemo Sensitivity to Guide Therapy

Progression-free survival time was defined as the time from initiation of study treatment to the first date of disease progression or death as a result of any cause. Progression was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Time was censored at the date of the last follow-up visit for patients who were still alive and have not progressed. The two-year progression free survival rate is a percentage, representing the fraction of treated patients who, after two years, are disease free or alive.

The percentage of patients with completely resected NSCLC tumors who had successful genomic analysis and assigned to treatment among patients. All 31 patients enrolled in the study had completely resected tumors. These tumors included a mixture of squamous and non-squamous histologies as indicated the original protocol. However, an amendment dated January 25, 2010 limited eligibility to patients with non-squamous disease. Given that only 5 patients were accrued into the study after this amendment, results reported will consider all histologies.

Overall survival time was defined as the time from initiation of study treatment to the date of death as a result of any cause. Time was censored at the date of the last follow-up visit for patients who were still alive. The two-year overall survival rate is a percentage, representing the fraction of treated patients who, after two years, are alive

Do to space limitations, see the Detailed Description in the study protocol for the wording of the questions used in the Patient Expectations Questionnaire.

Using genomics-based prediction models previously developed separately for cisplatin and pemetrexed, the probability that each patient was sensitive or would respond to treatment was computed. Quartiles describe the patterns of drug sensitivity probabilities. The 1st, 2nd, and 3rd quartiles are the sensitivity levels at which 25%, 50%, and 75% of patients have lower sensitivity. There is lack of integrity regarding the available data due to irreproducible genomic signatures. Therefore the results of this outcome are not presented.

Eli Lilly and Company

Duke University

No adverse events were observed for patients considered screen failures.

Arm A-Vinorelbine

Arm B-Pemetrexed

Patients who were registered and underwent protocol-based procedure (e.g. biopsy, genomic screening), but were not assigned to or administered genomics-directed, protocol-based therapy.

Note that two patients who were assigned protocol-based treatment (1 in each arm) did not receive the treatment and were added to the 7 initially identified as screen failures within the summary of baseline characteristics and outcome measures.

Screen Failures

Total

United States

Region of Enrollment

One patient in each of the vinorelbine and pemetrexed arms did not undergo protocol-based treatment, resulting in 22 total patients who were treated with either vinorelbine or pemetrexed. These two enrolled patients who were not administered treatment were added to the 7 original screen failures.

Neal Ready, PhD, MD

Treatment refers to patients treated in the combined vinorelbine and pemetrexed arms of the study. Due to the irreproducibility of the genomics-based prediction model for assigning patients into the original cisplatin treatment arms, patients from both arms were combined for primary outcome analysis.

Treatment

Due to the irreproducible nature of the genomic signatures of chemotherapeutic sensitivity, analyses based on separate treatment groups were inappropriate. Therefore, all enrolled participants (initiated for treatment) from both treatment arms were analyzed together.

2-Year Progression-Free Survival Rate in Patients With Completely Resected Stage IB, II, or IIIA NSCLC

All registered/enrolled patients are included in this outcome, which was measured at the time of consent.

All Registered Patients

Percentage of Patients With Completely Resected NSCLC Tumors That Can Be Analyzed and Used to Direct Adjuvant Chemotherapy

Treatment refers to patients treated in the combined vinorelbine and pemetrexed arms of the study.

2-Year Overall Survival in Patients Treated for NSCLC

Twenty-six questionnaires were returned. There was insufficient numbers to provide for substantive analysis.

Patient Understanding and Perceptions of Participating in a Clinical Trial Evaluating Cancer Genomics for Adjuvant Treatment of Early Stage Lung Cancer

There is lack of integrity regarding the available data due to irreproducible genomic signatures. Therefore the results of this outcome are not presented.

Compare Drug Sensitivity Patterns of Cisplatin and Pemetrexed in Both Treatment Arms

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Molecular-Guided Therapy for Childhood Cancer	NCT02162732	Neuroblastoma Medulloblastoma Glioma Ependymoma Choroid Plexus ... Craniopharyngio... Dysembryoplasti... Meningioma Primitive Neuro... Germ Cell Tumor... Rhabdomyosarcom... Non-rhabdomyosa... Ewings Sarcoma Osteosarcoma Wilms Tumor Renal Cell Carc... Malignant Rhabd... Clear Cell Sarc... Liver Tumors	Guided Therapy	13 Months - 21 Years	Milton S. Hershey Medical Center
Adjuvant Cisplatin With Either Genomic-Guided Vinorelbine or Pemetrexed for Early Stage Non-Small-Cell Lung Cancer	NCT00545948	Carcinoma, Non-...	Vinorelbine fol... Pemetrexed foll...	18 Years -	Duke University

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