Neoplasms

All Conditions

Digestive System Diseases

Symptoms and General Pathology

Carcinoma

Carcinoma, Hepatocellular

Recurrence

Liver Cirrhosis

Liver Neoplasms

Neoplasm Recurrence, Local

Fibrosis

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Liver Diseases

Gastrointestinal Diseases

Disease Attributes

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Neoplastic Processes

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Gemcitabine

Cisplatin

Oxaliplatin

Liver Extracts

Ethiodized Oil

Antimetabolites

Oxaliplatin, gemcitabine, cisplatin, lipiodol

Eric Savier, MD

Besides liver transplantation, the curative treatment of primary hepatic cancer with cirrhosis remains the surgical resection. Radiofrequency or cryotherapy currently allow local ablation of small cancer, with very good results. However, all these treatments are followed by high rates of recurrence (50 - 70% at 5 years). Then, it seems essential to associate to the surgical resection or to the local ablation as "adjuvant" treatment, in order to prevent or to decrease the rate of recurrence. However, no evidence supports this attitude. Therefore, following curative treatment of primary hepatic cancer with cirrhosis, we propose to compare treated to untreated patients. Postoperative treatment means either intra-arterial chemotherapy or systemic chemotherapy. The main criterion of the study is time of survival without recurrence. The main secondary objective is the safety.

The best treatment for hepatocellular carcinoma (HCC) with cirrhosis, currently is liver transplantation because treating the cancer and the causal disease. For the majority of patients, transplantation is not proposed, and the curative treatment remains the surgical resection. Radiofrequency or cryotherapy currently allows local destruction (or ablation) of the small HCC, with results that seem equivalent to the surgical resection. These last techniques increase the therapeutic possibilities in the presence of hepatic insufficiency. However, all these treatments are followed by high rates of recurrence (50 - 70% at 5 years and close to 100% at 10 years). The development of tumoral nodules, undetected at the time of the curative treatment, or the occurrence of new HCC, under the effects of the cirrhotic process or viral genomic modifications explain these disappointing results. Therefore, it seems essential to associate an adjuvant treatment to the surgical resection or the local destruction. Intra-arterial chemotherapy with or without embolisation is a largely evaluated therapeutic approach whose results are contradictory. Several retrospective studies, seem nevertheless to show a benefit of this treatment in adjuvant situation. Systemic chemotherapy for a long time regarded as ineffective, currently has a renewed interest due to the use of new drugs like gemcitabine and oxaliplatin (GEMOX regimen). This regimen showed a certain effect in a phase II study in advanced forms of HCC with cirrhosis. We propose to test by a prospective randomized multicentric phase III study, the effectiveness of an adjuvant treatment by systemic chemotherapy or intra-arterial LIPIODOLISED chemotherapy (CIAL), after surgery or complete local destruction of HCC. Three groups will be compared: a group of untreated patients (n=109), a group of patients treated by intra-arterial chemotherapy (CIAL = cisplatin 75 mg + lipiodol 10 ml; 3 courses every 6 weeks)(n=77) and a group of patients treated by systemic chemotherapy (GEMOX= day 1: gemcitabine 1000 mg/m² iv within 100 min; day 2: oxaliplatin 100 mg/m² iv within 2h; 8 courses every 2 weeks, d1 = d14)(n=77). Selection and randomisation are planned 4-8 weeks following complete treatment of the HCC. Identical follow up for the 3 groups includes clinical, biological, morphological exams every 3 months for 2 years, then every 6 months for 3 years. The main criterion of the study is survival without recurrence. The secondary objectives are the global survival, the safety and an estimate of the costs of the various treatments. The awaited results are 1) to demonstrate the effectiveness of at least one of these adjuvant treatment following complete treatment of HCC in cirrhotic patients and 2) to determine the best adjuvant treatment. Estimated inclusion time is 2 years, with an analysis of the principal criterion at 3 years. Follow-up of 5 years is envisaged for each patient, leading to a 7 years duration study.

Chemotherapy or Not, Following Complete Treatment of Hepatic Cancer in Cirrhotic Patients

Arterial LIPIODOLISED Chemotherapy Versus Systemic Chemotherapy With Gemcitabine Plus Oxaliplatin (GEMOX) Versus no Treatment Following Surgical Resection or Local Ablation of Hepatocellular Carcinoma in Cirrhotic Patients

Assistance Publique - Hôpitaux de Paris

Isabelle Brindel

Infections

Blood and Lymph Conditions

Immune System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Nervous System Diseases

Rare Diseases

Syndrome

Lymphoma

Lymphoma, Non-Hodgkin

Communicable Diseases

Acquired Immunodeficiency Syndrome

HIV Infections

Immunologic Deficiency Syndromes

Nervous System Neoplasms

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Anti-Infective Agents

Antirheumatic Agents

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Micronutrients

Dermatologic Agents

Reproductive Control Agents

Bone Density Conservation Agents

Vitamins

Cytarabine

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Dexamethasone

Molgramostim

Sargramostim

Leucovorin

Levoleucovorin

Methotrexate

Vincristine

Calcium

Dexamethasone acetate

Bleomycin

Calcium, Dietary

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Antiviral Agents

Antidotes

Protective Agents

Trace Elements

Tubulin Modulators

Antimitotic Agents

Folinic Acid

Folate

Vitamin B9

Bleomycin sulfate

Vincristine sulfate

Doxorubicin hydrochloride

Leucovorin calcium

Walsh C

Levine AM

To determine the toxicity and effectiveness of adding sargramostim (recombinant granulocyte-macrophage colony stimulating factor; GM-CSF) to a standard chemotherapy drug combination (methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone) known as mBACOD in the treatment of non-Hodgkin's lymphoma in patients who are infected with HIV.

Treatment of patients with AIDS-associated lymphoma is achieving inferior results when compared with outcomes for non-AIDS patients. Treatment with mBACOD has been promising, but the toxicity is very high. Patients treated with mBACOD have very low white blood cell counts. GM-CSF has increased the number of white blood cells in animal studies and preliminary human studies. It is hoped that including GM-CSF among the drugs given to lymphoma patients will prevent or lessen the decrease in white blood cells caused by mBACOD.

Treatment of patients with AIDS-associated lymphoma is achieving inferior results when compared with outcomes for non-AIDS patients. Treatment with mBACOD has been promising, but the toxicity is very high. Patients treated with mBACOD have very low white blood cell counts. GM-CSF has increased the number of white blood cells in animal studies and preliminary human studies. It is hoped that including GM-CSF among the drugs given to lymphoma patients will prevent or lessen the decrease in white blood cells caused by mBACOD.

Patients admitted to the study receive chemotherapy in 21-day cycles. The length of therapy, 2 - 8 months, depends on how the tumor responds to treatment. Four medicines are given on day 1 of each cycle by vein (IV) (doxorubicin, cyclophosphamide, bleomycin, vincristine). Dosages of doxorubicin and cyclophosphamide are increased in later groups of patients if toxicity in the first group is tolerable. A fifth medicine (dexamethasone) is given by mouth (PO) on days 1 - 5 of each cycle and the sixth medicine (methotrexate) is given IV on day 15 of each cycle. Leucovorin is given after methotrexate to prevent methotrexate side effects. GM-CSF treatment is started on day 3 and continued for 11 days. To prevent the spread of the tumor, a spinal tap is done on 4 occasions to inject cytosine arabinoside directly into the spinal fluid. If tumor cells are present in the spinal fluid, the patient also takes cytosine arabinoside by spinal tap 3 x/week until the tumor cells disappear and then at monthly intervals for 1 year. Patients with tumor cells in the spinal fluid are also given radiation treatment to the head.

Phase I Trial of mBACOD and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in AIDS-Associated Large Cell, Immunoblastic, and Small Non-cleaved Lymphoma

National Institute of Allergy and Infectious Diseases (NIAID)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Chemotherapy or Not, Following Complete Treatment of Hepatic Cancer in Cirrhotic Patients	NCT00470340	Liver Neoplasms Liver Cirrhosis Carcinoma, Hepa... Recurrence Neoplasm Recurr...	Oxaliplatin, ge...	18 Years - 75 Years	Assistance Publique - Hôpitaux de Paris
Phase I Trial of mBACOD and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in AIDS-Associated Large Cell, Immunoblastic, and Small Non-cleaved Lymphoma	NCT00000689	Lymphoma, Non-H... HIV Infections	Bleomycin sulfa... Vincristine sul... Doxorubicin hyd... Cyclophosphamid... Methotrexate Cytarabine Leucovorin calc... Sargramostim Dexamethasone	13 Years -	National Institute of Allergy and Infectious Diseases (NIAID)
Chemotherapy or Not, Following Complete Treatment of Hepatic Cancer in Cirrhotic Patients	NCT00470340	Liver Neoplasms Liver Cirrhosis Carcinoma, Hepa... Recurrence Neoplasm Recurr...	Oxaliplatin, ge...	18 Years - 75 Years	Assistance Publique - Hôpitaux de Paris
Phase I Trial of mBACOD and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in AIDS-Associated Large Cell, Immunoblastic, and Small Non-cleaved Lymphoma	NCT00000689	Lymphoma, Non-H... HIV Infections	Bleomycin sulfa... Vincristine sul... Doxorubicin hyd... Cyclophosphamid... Methotrexate Cytarabine Leucovorin calc... Sargramostim Dexamethasone	13 Years -	National Institute of Allergy and Infectious Diseases (NIAID)
Chemotherapy or Not, Following Complete Treatment of Hepatic Cancer in Cirrhotic Patients	NCT00470340	Liver Neoplasms Liver Cirrhosis Carcinoma, Hepa... Recurrence Neoplasm Recurr...	Oxaliplatin, ge...	18 Years - 75 Years	Assistance Publique - Hôpitaux de Paris

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