Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effect of Low Molecular Weight Heparin on Survival of Stage I,II or IIIA Non Small Cell Lung Cancer. A Multicenter, Open, Randomized Controlled Trial.
Brief Summary: Experiments suggest that low molecular weight heparin (LMWH) inhibits tumor growth and metastasis. Studies in humans suggest that LMWH is associated with a higher survival in patients with cancer related thrombosis. Two recent studies suggest that LMWH may increase the survival of patients with cancer who do not have an associated thrombosis. The purpose of the study is to assess the effect of LMWH on the overall survival of patients with localized non-small cell lung cancer after complete surgical resection.


Options:
A: Inclusion Criteria:

* Participants must meet the following criteria on screening examination to be eligible to participate in phase 2 and 3 of the study:
* Participants must have histologically confirmed malignancy that is metastatic or currently unresectable.
* Eligible malignancies include:

  * Adenocarcinoma of the pancreas (currently unresectable or metastatic)
  * Colorectal (stage IV)
  * Non-small cell lung cancer (currently unresectable stage III or stage IV)
* Receiving or scheduled to receive first or second line chemotherapy (within 30 days of registration)
* Minimum age 18 years. Because limited dosing or adverse event data are currently available on the use of isoquercetin in participants \<18 years of age, children are excluded from this study but will be eligible for future pediatric isoquercetin trials.
* Life expectancy of greater than 4 months.
* ECOG performance status ≤2 (see Appendix B ).
* Patient must be able to swallow capsules (phase III only)
* Participants must have preserved organ and marrow function as defined below:

  * Absolute neutrophil count ≥1,000/mcL
  * Platelets ≥ 90,000/mcL
  * PT and PTT ≤ 1.5 x upper limit of normal
  * Total bilirubin \< 2.0 mg/dl
  * AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional upper limit of normal Creatinine \< 2.0 mg/dl
* The effects of isoquercetin on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
* Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* Participants may not be receiving any other study agents.
* Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
* Prior history of documented venous thromboembolic event within the last 2 years (excluding central line associated events whereby patients completed anticoagulation).
* Active bleeding or high risk for bleeding (e.g. known acute gastrointestinal ulcer)
* History of significant hemorrhage (requiring hospitalization or transfusion) outside of a surgical setting within the last 24 months
* Familial bleeding diathesis
* Known diagnosis of disseminated intravascular coagulation (DIC)
* Currently receiving anticoagulant therapy
* Current daily use of aspirin (\>81mg daily), Clopidogrel (Plavix), cilostazol (Pletal), aspirin-dipyridamole (Aggrenox) (within 10 days) or considered to use regular use of higher doses of non-steroidal anti-inflammatory agents as determined by the treating physician (e.g ibuprofen \> 800 mg daily or equivalent).
* Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Known intolerance of niacin or ascorbic acid (including known G6PD deficiency)
* Pregnant women are excluded from this study because isoquercetin is a PDI inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with isoquercetin, breastfeeding should be discontinued if the mother is treated with isoquercetin. These potential risks may also apply to other agents used in this study.
B: Inclusion Criteria:

Patients with completely resected non-small cell lung cancer of stage I, II, or IIIA T3N1 confirmed by histology can be included in the study Patients who had preoperative chemotherapy, those who are selected for adjuvant chemotherapy and those who are not candidates for adjuvant chemotherapy (because they have a contraindication to chemotherapy or they have a stage I cancer) are eligible for the study Written informed consent age \> 18 years

Exclusion Criteria:

Previous heparin induced thrombocytopenia Allergy to tinzaparin Allergy to sulfites Renal failure with a creatinin clearance \< 30 ml/min according to COCKROFT formula Prothrombin time \< 50% Platelet count \< 100 G/L Increased bleeding risk: ongoing hemorrhage, major bleeding within 10 days, previous intracerebral bleeding, uncontrolled hypertension (SAP \> 180 mmHg or DAP \> 120 mmHg) Indication for curative anticoagulant treatment on inclusion More than 6 weeks between surgery and inclusion Known pregnancy or no efficient contraception for women of childbearing age Breast feeding Previous malignant disease diagnosed within 2 years except in situ carcinoma of the uterine cervix or spinal-cellular or baso-cellular cutaneous carcinoma Inclusion in another therapeutic trial at the time of inclusion Treatment with an experimental drug within 30 days before inclusion in the study
C: Inclusion Criteria:

* cancer patients with a first diagnosis of unsuspected PE

Exclusion Criteria:

1. age \<18 years;
2. ongoing anticoagulant therapy for previous VTE or indications for long-term anticoagulation other than deep vein thrombosis (DVT) or PE;
3. life expectancy less than 3 months.
D: Inclusion Criteria:

* Patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements.
* Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
* Patient is 65 years old or younger at the time of signing the informed consent
* Female patient is either post-menopausal or surgically sterilized or willing to use an acceptable double method of birth control (i.e., a hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
* Negative serum β-human chorionic gonadotropin ( β-HCG) pregnancy test both 24 hours prior to beginning of therapy and then at 4 weeks intervals in women with regular menstrual cycles or every 2 weeks in women with irregular menstrual cycles during study treatment for subjects of childbearing potential
* Male patient agrees to use an acceptable method for contraception (i.e., condom or abstinence) during study drug therapy (including dose interruption) and for 4 weeks after discontinuation of lenalidomide therapy.
* Patient was diagnosed with symptomatic multiple myeloma based on standard criteria (9), and has measurable disease, defined as follows: any quantifiable serum monoclonal protein value (generally, but not necessarily, greater than 1 g/dL of IgG M-Protein and greater than 0.5 g/dL of IgA M-Protein) and, where applicable, urine light-chain excretion of \>200 mg/24 hours; measurable plasmacytoma \> 2 cm as determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan); bone marrow plasma cells\>10%.
* Patient has a Karnofsky performance status ≥ 60%.
* Patient has a life-expectancy \> 6 months
* Patient has not active infectious hepatitis type B or C, and has HIV negative test
* Patients must have an ejection fraction by ECHO or MUGA \> 50% performed within 60 days prior to registration
* Patients must have adequate pulmonary function studies \> 50% of predicted on mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) \> 50% of predicted. Patients unable to complete pulmonary function tests because of myeloma-related chest pain, must have a high resolution CT scan of the chest and must also have acceptable arterial blood gases defined as P02 greater than 70.
* Patient has the following laboratory values within 14 days before Baseline (day 1 of the Cycle 1):

  * Platelet count ≥ 75 x 109/L without transfusion support within 7 days before the test.
  * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L without the use of growth factors.
  * Corrected serum calcium ≤ 14 mg/dL (3.5 mmol/L).
  * Aspartate transaminase (AST): ≤ 2.5 x the upper limit of normal (ULN).
  * Alanine transaminase (ALT): ≤ 2.5 x the ULN.
  * Total bilirubin: ≤ 1.5 x the ULN.
  * Calculated or measured creatinine clearance: ≥ 30 mL/minute
* Patient has a baseline bone marrow sample available for cytogenetics, that will be processed and eventually centralized within each country.

Exclusion Criteria:

* Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid; \< to the equivalent of dexamethasone 40 mg/day for 4 days).
* Any serious medical condition, including the presence of laboratory abnormalities, which places the subject at an unacceptable risk if he or she participates in this study or confounds the experimental ability to interpret data from the study.
* Pregnant or lactating females.
* Prior history of malignancies, other than multiple myeloma, unless the subject has been free of the disease for ≥ 3 years. Exceptions include the following: Basal cell carcinoma of the skin, Squamous cell carcinoma of the skin, Carcinoma in situ of the cervix, Carcinoma in situ of the breast, Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)
* Neuropathy of ≥ grade 2 severity.
* Patients previously diagnosed as bearing deep venous thrombosis or arterial thromboembolic event within the latest 12 months, or bearing a clear indication for anti-platelet or anticoagulant therapy or bearing a high risk of bleeding complications are ineligible for the sub-study protocol.

Answer: B