Symptoms and General Pathology

All Conditions

Neoplasms

Musculoskeletal Diseases

Recurrence

Neoplasm Metastasis

Bone Neoplasms

Bone Diseases

Anlotinib QD po and it should be continued until disease progression or intolerable toxicity or patients withdrawal of consent

Anlotinib

Yang Yao

To evaluate the safety and efficacy of patients with recurrent and metastatic bone tumors.

Study of Anlotinib in Patients With Primary Malignant Bone Tumors

A Single-Arm, Open-Label, Multicenter Clinical Trial With Anlotinib Hydrochloride Capsule for Primary Malignant Bone Tumors With Recurrence and Distant Metastases

From random grouping to the objective progression or death of a tumor

The time in which the group begins to cause death for any reason

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Rare Diseases

Sarcoma

Soft Tissue Neoplasms

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Registration according to approved data sets

Registration

Bruno Fuchs, MD PhD

Registration of all sarcoma patients treated at a specialized sarcoma center in Switzerland.

SCIENTIFIC BACKGROUND OF STUDY, EXPECTED OUTCOME, AND RELEVANCE Sarcomas represent malignant bone and soft tissue tumours. Overall, these are very rare tumours representing less than 1% of all cancers (besides carcinomas and haematological cancers). Furthermore, with the advent of molecular knowledge, more than 100 subtypes of sarcomas can be distinguished and many of them share a distinct biological behaviour opening the possibility of targeted therapy. The management of patients with sarcomas is extremely complex and highly multidisciplinary, involving the pathologist, the orthopaedic oncologist, a paediatric and medical oncologist, the radiation oncologist, the reconstructive as well as visceral and chest surgeon. Surgery remains the mainstay of treatment, but almost always in combination with either radiotherapy or chemotherapy, or novel targeted therapy. The key of successful therapy (and consequent successful outcome for the patient) remains the orchestrated team approach among these disciplines where the therapeutic strategy is interdisciplinary determined at the sarcoma board. Unfortunately, all too often and still nowadays, patients also in Switzerland are not treated within such a network. E.g., too many surgeons still believe that they are capable to remove a soft tissue lump (which technically is true), just to send the patient off after surgery to the medical oncologist, and never see the patient again. All too often this may result for example in an unnecessary amputation, a devastating consequence for the patient. A surgeon needs to be aware of the interpretation of the pathologic specimen, the possibilities of adjuvant treatment, and most importantly, the biology of each subtype of sarcoma, before embarking on surgery. Because of all the reasons listed above, it is very reasonable to centralize the treatment of sarcoma patients to improve the treatment and outcome for sarcoma patients in Switzerland, as is foreseen by the current initiative of HSM by the GDK. It is very important to state that such uncoordinated treatment of sarcoma patients with the potential deleterious consequences is an international phenomenon. Many groups have independently established that the lack of interdisciplinarity leads to worse patient outcome and survival. Many reasons account for this: rarity of disease, lack of knowledge, lack of awareness, and all too often also pride and prestige. The only way out is to bring treating physicians together and to make the institutions aware that applying simple management strategies -such as coordinated treatment- does improve the outcome of sarcoma patients, which has been proven in many countries already. Nowadays in Switzerland, there are only very few groups/institutions who deal exclusively with sarcoma patients. Consequently, the therapeutic approach and quality are varying a lot. Therefore, the establishment of a Swiss Sarcoma Cohort Study (SwissSARCOS) is instrumental in improving the quality of treatment, which has already been shown in other countries. If all patients are registered including their respective follow-up, the type of treatment can be registered and the various geographic regions can be compared with respect to patients' outcome. It can be expected that the awareness of treating a sarcoma patient according to international standards will be increased, for the benefit of the patient. Importantly, such registration will provide the base to participate in international studies in form of clinical trials, which is a prerequisite and also requested by the HSM, and will further improve the quality of the therapy of sarcoma patients in Switzerland. Such cohort study will also allow to assess the prevalence of sarcoma types in Switzerland, with its associated regional differences. Because of its rarity, registering all sarcoma types in Switzerland will bring together sizeable numbers and therefore will provide the base for numerous outcome studies. Because it is known that sarcomas are extremely heterogeneous and are molecularly defined, studying molecular alterations in tumour tissue is essential to advance the field. The French Sarcoma Group (Prof. JM.Coindre, F.Chibon) has started such initiative decades ago and are therefore leaders in this field. The investigators therefore speculate that SwissSARCOS ultimately will also provide a strong base to establish a sarcoma tissue bank which allows the study of molecular alterations on the one hand, but on the other hand to correlate these findings with clinical outcome. For these reasons outlined above, the establishment of SwissSARCOS is crucial to improve treatment quality of sarcoma patients in Switzerland.

The specific questions addressed within the first 2-year time period include: 1.) what is the prevalence of which sarcoma type in Switzerland; 2.) What is the quality of the (correct) diagnosis?; 3.) What is the quality of treatment?; 4.) What is the outcome (survival, local recurrence, metastasis etc.) of sarcoma patients in Switzerland? Complete identification and thorough assessment of the basic clinical parameters ("minimal data set") of sarcoma patients treated in Switzerland in a prospective manner will allow to improve the quality of patient care as outlined above. This is also in line with the national strategy to register all cancer patients. Therefore, this effort is very timely and has direct impact on public health issues. As shown for other cohort studies in Switzerland (e.g. HIV), such assessment of clinical parameters has widespread implications not only on the standard of patient care, but also on addressing important clinical research questions, thereby becoming a very relevant health care issue. Through such coordinated and orchestrated approach, Switzerland will become a key player for international collaborations to improve the treatment for sarcoma patients. It is very clear that it cannot be expected to include every single patient diagnosed with sarcoma of whole Switzerland right from the beginning. Obviously, it is the intention to first set a strong base with national key players and institutions, and then to strengthen this collaborative network to become a national instrument. The network of national key players and institutions should allow to bring all the regional efforts to a national level. The Sarcoma Center Zurich (www.sarkomzentrum.ch) is certified as a center of excellence by the German Cancer Society (DKG= Deutsche Krebsgesellschaft) since December 2013, the very first one in Switzerland. The Sarcoma Center in Zurich bases on the instrumental efforts of the cantonal government ("Regierungsrat") to specifically support the multidisciplinary team approach in musculoskeletal oncology, both on the clinical and research side since 2010 by the HSM program (www.sarkomboard.ch). Over the years, collaboration with all major regional hospitals in Switzerland was set up. All the collaborators of these hospitals have assembled to strengthen the goal to build up a Sarcoma Cohort Study. For that reasons the Sarcoma Center Zurich has the lead for this multicentre study and the ethic committee of Zurich is chosen as the leading committee.

Future: Molecular analyses of sarcoma tissue are the key for the advancement of the treatment strategies of sarcoma patients. Again based on the HSM program funded by the cantonal government in Zurich, tumour tissue specimens as well as blood is collected and stored of each single patient operated for a sarcoma in Zurich. This allows addressing fundamental molecular questions via TMA (tissue microarray analyses), the characterization of molecular markers, both in-vitro and in-vivo, proteomic diagnostic analyses, and novel targeted treatment approaches (please refer to www.sarkomzentrum.ch). It is foreseen that in the second phase of this grant project -and after having established the fundamentals of the national cohort study- to extend the efforts to not only gather patient data ("minimal data set"), but also tumour tissue/blood from the sarcoma patients treated in Switzerland.

In a further next step, and again based on these efforts outlined above with a nationally well documented patient cohort, the base will be set to participate in international clinical trials to test for example novel drug compounds or novel diagnostic imaging tools.

National Swiss Sarcoma Cohort Study

Prospective Multi-center National Swiss Sarcoma Cohort Study

Assessed data shall be shared with the National Institute for Cancer Epidemiology an Registration and the cantonal cancer registers

University of Bern

Balgrist University Hospital

Blood and Lymph Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Immune System Diseases

Nervous System Diseases

Heart and Blood Diseases

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Leukemia

Breast Neoplasms

Adenocarcinoma

Pancreatic Neoplasms

Glioma

Osteosarcoma

Carcinoma, Renal Cell

Lung Neoplasms

Lymphoma

Hematologic Neoplasms

Ataxia

Cerebellar Ataxia

Leukemia, T-Cell

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Telangiectasis

Kidney Neoplasms

Ataxia Telangiectasia

Colorectal Neoplasms

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Neoplasms, Glandular and Epithelial

Neoplastic Processes

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Breast Diseases

Skin Diseases

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Hematologic Diseases

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Pancreatic Cancer

Renal Cell Carcinoma

Lymphosarcoma

Acute Graft Versus Host Disease

Leukemia, T-cell, Chronic

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Irinotecan

Doxorubicin

Liposomal doxorubicin

Lomustine

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Topoisomerase I Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Drugs: Gemcitabine - 21 day cycle. 9-ING-41

Drugs: Nab-paclitaxel. Gemcitabine - 28 day cycle. 9-ING-41.

Drugs: Paclitaxel. Carboplatin. 9-ING-41.

Starting dose of-9-ING-41 will be administered on Day 1 and 4 each week of a 21-day cycle. 9-ING-41 will be administered intravenously over 60 minutes.

9-ING-41

Gemcitabine 1250 mg/m2 as a 30-minute intravenous infusion on Days 1 and 8 of a 21-day cycle

Gemcitabine - 21 day cycle

Doxorubicin 75 mg/m2, intravenous bolus on Day 1 of a 21-day cycle up to a maximum lifetime dose of 550 mg/m2.

Doxorubicin.

Lomustine 30 mg/m² orally as a single dose, weekly for twelve weeks.

Carboplatin AUC 6 IV over 1 hour on Day 1 of a 21-day cycle.

Carboplatin.

Nab-paclitaxel 125 mg/m2 intravenously on Days 1, 8 and 15 of a 28-day cycle

Nab paclitaxel.

Paclitaxel 175 mg/m2 intravenously over 3 hours on Day 1 of a 21-day cycle.

Paclitaxel.

Gemcitabine 1000 mg/m2 intravenously over 30-minutes on Days 1, 8 and 15 of a 28-day cycle

Gemcitabine - 28 day cycle

Irinotecan 350 mg/m2 intravenously over 90-minutes on Day 1 of a 21-day cycle

GSK-3β is a potentially important therapeutic target in human malignancies. The Actuate 1801 Phase 1/2 study is designed to evaluate the safety and efficacy of 9-ING-41, a potent GSK-3β inhibitor, as a single agent and in combination with cytotoxic agents, in patients with refractory cancers.

9-ING-41 is a first-in-class, intravenously administered, maleimide-based small molecule potent selective GSK-3β inhibitor with significant pre-clinical antitumor activity. GSK-3 is a serine/threonine kinase initially described as a key regulator of metabolism and has a role in diverse disease processes including cancer, immune disorders, pathologic fibrosis, metabolic disorders, and neurological disorders. GSK-3 has two ubiquitously expressed and highly conserved isoforms, GSK-3α and GSK-3β, with both shared and distinct substrates and functional effects. GSK-3β is particularly important in tumor progression and modulation of oncogenes (including beta-catenin, cyclin D1 and c-Myc), cell cycle regulators (e.g. p27Kip1) and mediators of epithelial-mesenchymal transition (e.g. zinc finger protein SNAI1, Snail). Aberrant overexpression of GSK-3β has been shown to promote tumor growth and chemotherapy resistance in various solid tumors including colon, ovarian, and pancreatic cancers and glioblastoma through differential effects on the pro-survival nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and c-Myc pathways as well on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and p53-mediated apoptotic mechanisms. GSK-3β helps maintain malignant cell survival and proliferation, particularly in terms of mediating resistance to standard anti-cancer therapies, through the NF-κB pathway. GSK-3β has been established as a potential anticancer target in human bladder, breast, colorectal, glioblastoma, lung, neuroblastoma, ovarian, pancreatic, prostate, renal and thyroid cancers as well as chronic lymphocytic leukemia and lymphomas.

9-ING-41 is a small molecule potent selective GSK-3β inhibitor with broad spectrum pre-clinical antitumor activity. It's modes of action include downregulation of NF-κB and decreasing the expression NF-κB target genes including cyclin D1, Bcl-2, anti-apoptotic protein (XIAP) and B-cell lymphoma-extra large (Bcl-XL) leading to inhibition of tumor growth in multiple solid tumor cell and lymphoma lines and patient derived xenograft (PDX) models. NF-κB is constitutively active in cancer cells and promotes anti-apoptotic molecule expression. NF-κB activation is particularly important in cancer cells that have become chemo- and/or radio-resistant. 9-ING-41 also has significant activity in pre-clinical models of pathological pleural and pulmonary fibrosis. 9-ING-41 has significant in vitro and in vivo activity as a single agent and/or in combination with standard cytotoxic chemotherapies in a spectrum of solid tumors and hematological malignancies including bladder, breast, glioblastoma, neuroblastoma, pancreatic, sarcomas, and renal cancers as well as lymphomas.

The 1801 had three parts:

* Completed: Part 1 (9-ING-41 as monotherapy): The standard 3+3 dose escalation design will be applied to all dose cohorts until the Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) is identified.
* Completed: 9-ING-41 combined with standard anticancer agents: The 3+3 dose escalation study design will be used for 8 chemotherapy combination regimens (9-ING-41 plus gemcitabine, doxorubicin, lomustine, carboplatin, irinotecan, nab-paclitaxel plus gemcitabine, paclitaxel plus carboplatin, pemetrexed plus carboplatin) to identify the MTD/RP2D of each regimen.
* Part 3: A randomized Phase 2 study of 9-ING-41 either once or twice weekly with gemcitabine and nab-paclitaxel (GA) versus GA alone for patients with previously untreated metastatic or locally advanced pancreatic cancer is now open.

9-ING-41 in Patients With Advanced Cancers

Phase 1/2 Study of 9-ING-41, a Glycogen Synthase Kinase-3 Beta (GSK-3β) Inhibitor, as a Single Agent and Combined With Chemotherapy, in Patients With Refractory Hematologic Malignancies or Solid Tumors

The standard assessments used to assign a score to any affected organ system as per the NCI CTCAE 4.03 will be conduced at each protocol-specified timepoint.

To determine the 1-year survival rate of patients treated on the 9-ING-41 schedule chosen from the run-in stage of the study compared to the control arm

Actuate Therapeutics Inc.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Anlotinib in Patients With Primary Malignant Bone Tumors	NCT03527888	Neoplasm of Bon...	Anlotinib	14 Years - 70 Years	Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
National Swiss Sarcoma Cohort Study	NCT02775799	Sarcoma Neoplasm of Bon... Neoplasms Soft Tissue Sar... Soft Tissue Neo... Sarcoma of Bone	Registration	-	Balgrist University Hospital
9-ING-41 in Patients With Advanced Cancers	NCT03678883	Cancer Pancreatic Canc... Sarcoma Renal Cancer Refractory Canc... Refractory Neop... Refractory Non-... Pancreatic Aden... Resistant Cance... Neoplasm Metast... Neoplasm of Bon... Neoplasm, Breas... Neoplasm of Lun... Neoplasms,Color... Neoplasms Pancr... Malignant Gliom... Malignancies Malignancies Mu... Bone Metastases Bone Neoplasm Bone Cancer Pancreas Cancer Pancreatic Neop... Breast Neoplasm... Acute T Cell Le...	9-ING-41 Gemcitabine - 2... Doxorubicin. Lomustine Carboplatin. Nab paclitaxel. Paclitaxel. Gemcitabine - 2... Irinotecan	18 Years -	Actuate Therapeutics Inc.

Spots Global Cancer Trial Database for neoplasm of bone