Neoplasms

All Conditions

Digestive System Diseases

Adenocarcinoma

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Lipid Regulating Agents

Capecitabine

Simvastatin

Anticholesteremic Agents

Hypolipidemic Agents

Antimetabolites

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Enzyme Inhibitors

simvastatin

woon ki kang, professor

Statins are widely used as lipid-lowering agents to lower cardiovascular risk with a favorable safety profile. In our recent in vitro study, the addition of simvastatin to chemoradiotherapy with 5-FU showed synergistic anticancer effect in various colon cancer cells (unpublished data). So we planned this study to investigate the synergistic effect of simvastatin combined with capecitabine and radiotherapy in locally advanced rectal cancer patients.

1. Primary Objective: pathologic complete response rate
2. Secondary Objectives:

   1. rate of sphincter-sparing surgical procedure
   2. rate of R0 resection
   3. disease-free survival
   4. overall survival
   5. pattern of failure
   6. safety and toxicity
   7. lipid lowering effect of simvastatin

Capecitabine Plus Simvastatin in Locally Advanced Rectal Cancer Patients

A Single Arm, Phase II Study of Neoadjuvant Chemoradiotherapy With Capecitabine Plus Simvastatin in Locally Advanced Rectal Cancer Patients

pathologic complete response ratewill be shown with 95% confidence intervals

rate of sphincter-sparing surgical procedure

Time from randomization to death or last follow-up

Response rate according to RECIST 1,1 guideline will also be evaluated

Total cholesterol, LDL-cholesterol records. (2weeks)

Samsung Medical Center

Tissue specimen

Howard Safran, MD

The purpose of this study is to study which genes are abnormal in rectal cancer and see if this predicts how well chemotherapy and radiation will reduce the size of cancer and whether cancer recurs after surgery.

Specific gene mutations have become targets for specific therapies. For example lung adenocarcinomas with an EGFR (epidermal growth factor receptor) mutation can be targeted with an EGFR tyrosine kinase inhibitor achieve striking and durable responses and improved survival. Another example is the identification of the echinoderm microtubule-associated protein-like 4/anaplastic lymphoma kinase (ALK) gene fusions which have led to significant therapeutic gains in the small percentage of patients with lung adenocarcinoma whose cancers exhibit this mutation. Specific mutations have been found in colon cancer and specific drugs targeting these gene alterations are in development. As future therapeutic protocols specific for these mutations are developed, patients who agree may be notified of their eligibility for these studies.

The aims of this study are to link mutational analyses with clinical outcome. It is recommended that patients receive 8 cycles of mFOLFOX6 (modified FOLFOX) and 50.4 Gy radiation with concurrent fluoropyrimidine.

Tissue specimen from diagnosis from rectal cancer

Rectal Cancer Consortium

Rectal Cancer Consortium: BrUOG 285: A Comprehensive Program to Identify Therapeutic Targets and Develop Targeted Agents for Testing With Total Neoadjuvant Treatment for Stage II-III Rectal Cancer BrUOG= Brown University Oncology Research Group

Brown University

Principal Investigator

Symptoms and General Pathology

Neoplasm Metastasis

Folfirinox

FOLFORINOX

Jean-Baptiste BACHET, Dr

The FOLFIRINOX protocol seems a promising protocol as attack treatment of a rectum cancer, with an objective response rate of about 70 %. This phase II is to investigate if this systematic attack chemotherapy could control at the same time the rectal tumor and the synchronous metastasis without compromising secondarily the tumor or the metastasis resection or a radiochemotherapy administration.

1. The main objective of the trial is to investigate the tumoral control rate at 4 months, according to the RECIST criteria (version 1.1).
2. The secondary objectives are:

   * safety of the treament,
   * rate of local failure and local complication (occlusion, important bleedings, resistant pains with morphinic treatment, perforation),
   * survival without local failure (radiological or clinical progression of the rectal cancer or local complication),
   * rectal tumor response rate (CT scan, MRI and endocopy),
   * metastasis response rate,
   * disease free survival after complete resection (of primitive tumor and metastases),
   * progression free survival (local or distal),
   * overall survival, quality of life (QLQ-C30 + CR 29).

The FOLFIRINOX protocol seems a promising protocol as attack treatment of a rectum cancer, with an objective response rate of about 70 %. This phase II is to investigate if this systematic attack chemotherapy could control at the same time the rectal tumor and the synchronous metastasis without compromising secondarily the tumor or the metastasis resection or a radiochemotherapy administration.

1. The main objective of the trial is to investigate the tumoral control rate at 4 months, according to the RECIST criteria (version 1.1).
2. The secondary objectives are:

   * safety of the treament,
   * rate of local failure and local complication (occlusion, important bleedings, resistant pains with morphinic treatment, perforation),
   * survival without local failure (radiological or clinical progression of the rectal cancer or local complication),
   * rectal tumor response rate (CT scan, MRI and endocopy),
   * metastasis response rate,
   * disease free survival after complete resection (of primitive tumor and metastases),
   * progression free survival (local or distal),
   * overall survival, quality of life (QLQ-C30 + CR 29).
3. Inclusion and non inclusion criteria
4. Treatment
5. Follow up

First Line Treatment by FOLFIRINOX for Patients With a Rectum Cancer With Synchronous Non Resectable Metastasis

Phase II: First Line Treatment by FOLFIRINOX for Patients With a Rectum Cancer With Synchronous Non Resectable Metastasis

The tumor control rate of the primary site and metastasis is defined as Complete response or Partial response or stability according to RECIST 1.1 criteria

Number of patients presenting the main toxicities during the study

The rate is defined as the clinical progression or a radiological progression of the rectum cancer or a local complication due to the treatment or due to the progression

The survival time is defined as the time between the patient's inclusion and the time of the local failure or patient's death

The rectal tumor response rate is the Complete response or the Partial response of the rectal tumor using RECIST 1.1 criteria

The metastasis tumor response rate is the Complete response or the Partial response of metastasis using RECIST 1.1 criteria

Federation Francophone de Cancerologie Digestive

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Carcinoma

Multiple Myeloma

Neoplasms, Plasma Cell

Syndrome

Lymphoma

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Sarcoma

Hodgkin Disease

Preleukemia

Myelodysplastic Syndromes

Sarcoma, Ewing

Rhabdomyosarcoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Neoplasms, Connective and Soft Tissue

Bone Marrow Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Myeloproliferative Disorders

Myosarcoma

Osteosarcoma

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Myeloid Leukemia

Acute Myeloid Leukemia

Lymphosarcoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Acute Non Lymphoblastic Leukemia

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia

Soft Tissue Sarcoma

Hodgkin Lymphoma

Acute Graft Versus Host Disease

Ewing Sarcoma

Chronic Myeloproliferative Disorders

Two infusions of Natural Killer (NK) cells and ALT803

Two infusions of Natural Killer (NK) Cells

Dose escalation of Natural Killer (NK) Cells from two infusion of starting at Dose Level 1 (1x10\^7 cells/kg), dose Level-1 (1x10\^6 cells/kg) if 2 of 6 patients at Level 1 develop DLTs. Escalation to dose level 2 (2.5X10\^7) and Dose level 3 (5X10\^7) is dependent on DLT

Natural Killer (NK) Cells

ALT803

David Wald, MD, PhD

The purpose of this study is to find the number of natural killer (NK) cells from non-HLA matched donors that can be safely infused into patients with cancer. NK cells are a form of lymphocytes that defend against cancer cells. NK cells in cancer patients do not work well to fight cancer. In this study, the NK cells are being donated by healthy individuals without cancer who are not "matched" by human leukocyte antigen (HLA) genes to patients. After receiving these NK cells, patients may also be given a drug called ALT803. ALT803 is a protein that keeps NK cells alive, helps them grow in number and supports their cancer-fighting characteristics. HLA-unmatched NK cell infusion is investigational (experimental) because the process has not approved by the Food and Drug Administration (FDA).

Primary Objective:

To determine the maximum tolerated dose (MTD) of ex vivo expanded non-HLA matched donor NK cells in combination with ALT-803

Secondary Objectives:

* Describe safety profile / toxicity of combining ALT-803 with NK cell adoptive therapy.
* Determine antitumor activity of allogeneic NK cells with ALT-803 support.
* Determine if a lymphocyte depleting regimen is adequate for preventing early elimination of HLA-mismatched donor NK cells by host T-cells.

Study Design:

This is a phase I study with "3+3" design with three planned dose levels of NK cells and a fixed dose of ALT-803. Three patients will be enrolled sequentially to each dose level, starting with dose level 1. Patients will be segregated to either receive ALT803 as cytokine support after NK cell infusion (starting with same dose level as Level 1) or no cytokine administration. Patients in the arm receiving ALT803 will be either hematologic malignancy patients (Cohort A) or Colon/Soft tissue sarcoma patients (Cohort B). Absence of dose limiting toxicity (DLT) in the DLT assessment period of 28 days must be documented for all patients enrolled a cell dose without ALT803 before the next cohort of patients to receive cytokines at that dose level can be enrolled. Patients can also be enrolled in parallel to the next cell dose level without cytokines.

Phase I Trial of Universal Donor NK Cell Therapy in Combination With ALT803

Phase I Trial of Universal Donor NK Cell Therapy in Combination With ALT-803

MTD Will be determined by dose limiting toxicity (DLT). The MTD will be defined as the dose level immediately below that at which 2 of 6 subjects experience a dose limiting toxicity.

Measure of safety of natural killer (NK) cells in the absence of HLA matching

Complete Remission (CR): Bone marrow blasts \<5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count \>1.0x10\^9/L; platelet count \>100x10\^9/L.

CR with incomplete recovery (CRi): All CR criteria except residual neutropenia or thrombocytopenia.

Partial Remission (PR):Hematologic criteria of CR; decrease of bone marrow blast percentage to 5-25%; and decrease of pretreatment bone marrow blast percentage by ≥50%.

Cytogenetic CR (CRc): Reversion to normal karyotype at the time of morphologic CR.

Resistant disease (RD): Failure to achieve CR, CRi, or PR. Death in aplasia: Deaths occurring ≥7 days after initial treatment. Death from indeterminate cause: Deaths before completing therapy, or \<7 days following completion; or deaths occurring ≥7 days after therapy with no blasts in the blood Relapse: Bone marrow blasts ≥ 5%; or reappearance of blasts in the blood; or development of extramedullary disease

* Measurable disease: at least one measurable lesion.
* Measurable lesions: those that can be measured in at least one dimension as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan.
* Non-measurable lesions: all other lesions, including small lesions that are not confirmed and followed by imaging techniques.
* Baseline documentation of "Target" lesions: all measurable lesions up to a maximum of five lesions per organ and 10 lesions in total. Target lesions should be selected on the basis of their size and their suitability for accurate repeated measurements.
* Non-target lesions: all other lesions should be identified as non-target lesions. Non-target lesions include measurable lesions that exceed the maximum numbers per organ or total of all involved organs as well as non-measurable lesions.

Lymphoma response of Complete remission, partial remission, relapsed disease, stable disease, progressive disease and best response based on the Journal of Clinical Oncology criteria defined by Cheson in 2014

* Complete response (CR): complete disappearance of disease at and negative serum immunofixation.
* Partial response (PR): \>50% reduction of serum monoclonal protein concentration with \>50% reduction of tumor infiltrate and resolution of symptoms attributable to WM.
* Minor response (MR): \> 25% but l\<50% reduction of serum monoclonal immunoglobulin M (IgM) determined by protein electrophoresis and no new symptoms or signs of active disease.
* Stable disease: \< 25% reduction and \<25% increase of serum monoclonal IgM without progression of adenopathy, organomegaly, cytopenias, or clinically significant symptoms caused by disease and/or signs of WM.
* Progressive disease: fails to meet criteria for response or stable disease. Progression also requires at least a 25% increase of serum monoclonal protein from the lowest value or worsening of cytopenias, lymphadenopathy, or organomegaly, or appearance of disease-related complications.

CR/CCR

* Complete resolution of skin patches, plaques and tumors (or erythroderma)
* No evidence of abnormal lymph nodes
* Absence of circulating Sézary cells
* No evidence of new tumor (CCR) plus confirmation by skin biopsy (CR) PR
* ≥50% improvement in the summation of (∆ Skin + ∆ Lymph Node + ∆ Peripheral Blood) with at least ≥30% improvement in ∆ Skin
* No worsening in Lymph Node or Sézary cells
* No evidence of new tumors (cutaneous or non-cutaneous)

Stable Disease at 90 Days (SD90)

• Fails to meet criteria for PR or CR but absence of new cutaneous or non-cutaneous disease over 90 days

Progressive Disease (PD)

* ≥ 50% increase from nadir or baseline in styrylpyridine derivative (SPD) or any node or lesion
* ≥ 50% increase from nadir in gestational trophoblastic disease (GTD) of any node previously \>1cm in shortest diameter
* Appearance of any new cutaneous or non-cutaneous lesion during or at the end of therapy.

Stringent Complete Response (sCR)

* CR as defined below plus:

  • Normal FLC ratio and Absence of clonal cells in bone marrow CR
* Negative immunofixation on the serum and urine and:

  * Disappearance of any soft tissue plasmacytomas
  * ≤5% plasma cells in bone marrow Very good partial response (VGPR)
* Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \<100mg per 24h PR
* ≥ 50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥ 90% or to \<200 mg per 24h
* If the serum and urine protein are unmeasurable, ≥ 50% decrease in the difference between involved and uninvolved FLC levels is required
* If the serum and urine protein are unmeasurable, and serum free light assay is also unmeasurable, ≥ 50% decrease in plasmacells is required SD
* Not meeting criteria for CR, VGPR, PR, or progressive disease

Complete hematologic response

• White blood cell count \<10,000/microL with no immature granulocytes and \<5 percent basophils on differential, platelet count \<450,000/microL, and spleen not palpable.

Cytogenetic responses

* Complete cytogenetic response: No Philadelphia chromosome positive cells present.
* Partial cytogenetic response: 1 to 35 percent Philadelphia chromosome positive cells present.
* Major cytogenetic response includes patients with complete and partial cytogenetic response (ie, 0 to 35 percent Philadelphia chromosome positive cells present).
* Minor-minimal cytogenetic response: 36 to 95 percent Philadelphia chromosome positive cells present.

Molecular response:

* Complete molecular response: break cluster region - Abelson family kinases (BCR-ABL) transcript nondetectable and nonquantifiable in an assay that has at least 4 to 5 log range.
* Major molecular response: An at least three log reduction in BCR-ABL transcript levels from baseline.

Complete Response: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm (the sum may not be "0" if there are target nodes). Partial Response: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Progressive Disease: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions may be considered progression).

Stable Disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.

The duration of overall response is measured from the time of NK Cell infusion until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

Overall survival is measured from the date of first infusion of NK cells to the date of death from any cause; patients not known to have died at last follow up are censored on the date they were last known to be alive.

Only those patients achieving complete response (CR) or complete response with incomplete recovery (CRI). It is measured from the date of infusion of NK cells until the date of relapse or death from any cause; patients not known to have relapsed or died at last follow up are censored on the date they were last examined.

Measurement of in vivo NK cell levels following cell product infusion will be done on peripheral blood by flow cytometry (CD3- CD56+ positive cells). This will be done on peripheral blood samples of patients. Measurement of successful donor NK cell persistence (absence of cell product rejection) will be defined as measurement of \>100 NK cell/µL

Brenda Cooper, MD

Medical Oncology Specialist

Disease Progression

Neoplasms, Glandular and Epithelial

Colonic Diseases

Neoplastic Processes

Anti-Infective Agents

Micronutrients

Hematinics

Vitamins

Amino Acids

Etoposide

Gemcitabine

Vinorelbine

Paclitaxel

Irinotecan

Doxorubicin

Liposomal doxorubicin

Pemetrexed

Docetaxel

Cetuximab

Fluorouracil

Raltitrexed

Albumin-Bound Paclitaxel

Topotecan

Cisplatin

Oxaliplatin

Etoposide phosphate

Dasatinib

Mitomycins

Mitomycin

Sorafenib

Erlotinib Hydrochloride

Tubulin Modulators

Antimitotic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Antineoplastic Agents, Immunological

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Alkylating Agents

Folinic Acid

Folate

Vitamin B9

Tyrosine

Control treatment and will be treated with any of the schemes used in the study according to the discretion of the physician.

Treatment guided by the gene expression profiles obtained from the CTC

Arm A chemotherapy

arm B chemotherapy

Carlos Gómez, M.D.,Ph.D

The purpose of this study is to assess the feasibility of selecting personalized therapies for colon cancer patients who have failed standard treatments, using a new methodology based on the determination of a profile of chemosensitivity by comprehensive genetic expression analysis from tumor samples.

It is a prospective, randomized study in patients with metastatic colorectal carcinoma progressing after two lines of prior therapy. Patients will be randomized (1:1) to receive chemotherapy as determined by its oncologist or treatment according to chemosensitivity profile obtained. For obtaining the profile a histological tumor sample and a sample of venous blood in a tube with heparin standard are necessary . This latter sample will be processed to isolate circulating tumor cells by cell adhesion with matrix coated glass spheres. The RNA from these circulating tumor cells as well as from tumor cells of tumor biopsies from the same patients will be extracted by a standard procedure for extracting RNA for genetic expression analysis. Based on the analysis performed on tumor biopsy is generated a ranked list of potentially more effective treatments in every case

Study of Individualized Therapies Selection for Patients With Metastatic Colorectal Carcinoma According to the Therapeutic

Phase II Individualized Therapies Selection Study for Patients With Metastatic Colorectal Carcinoma According to the Genomic Expression Profile in Tumor Samples.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Capecitabine Plus Simvastatin in Locally Advanced Rectal Cancer Patients	NCT02161822	Adenocarcinoma ...	simvastatin	20 Years -	Samsung Medical Center
Rectal Cancer Consortium	NCT01835925	Rectal Cancer	Tissue specimen	18 Years -	Brown University
Capecitabine Plus Simvastatin in Locally Advanced Rectal Cancer Patients	NCT02161822	Adenocarcinoma ...	simvastatin	20 Years -	Samsung Medical Center
Rectal Cancer Consortium	NCT01835925	Rectal Cancer	Tissue specimen	18 Years -	Brown University
Capecitabine Plus Simvastatin in Locally Advanced Rectal Cancer Patients	NCT02161822	Adenocarcinoma ...	simvastatin	20 Years -	Samsung Medical Center
First Line Treatment by FOLFIRINOX for Patients With a Rectum Cancer With Synchronous Non Resectable Metastasis	NCT01674309	Adenocarcinoma ...	FOLFORINOX	18 Years -	Federation Francophone de Cancerologie Digestive
Phase I Trial of Universal Donor NK Cell Therapy in Combination With ALT803	NCT02890758	Acute Myeloid L... Myelodysplastic... Acute Lymphobla... Chronic Myeloid... Chronic Lymphoc... Non Hodgkin Lym... Hodgkin Lymphom... Myeloproliferat... Plasma Cell Mye... Colon Carcinoma Adenocarcinoma ... Soft Tissue Sar... Ewing's Sarcoma Rhabdomyosarcom...	Natural Killer ... ALT803	18 Years -	Case Comprehensive Cancer Center
Study of Individualized Therapies Selection for Patients With Metastatic Colorectal Carcinoma According to the Therapeutic	NCT01703910	Adenocarcinoma ... Adenocarcinoma ... Metastatic Dise...	Arm A chemother... arm B chemother...	18 Years - 76 Years	Centro Nacional de Investigaciones Oncologicas CARLOS III
Rectal Cancer Consortium	NCT01835925	Rectal Cancer	Tissue specimen	18 Years -	Brown University

Spots Global Cancer Trial Database for adenocarcinoma of rectum