Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Carcinoma, Squamous Cell

Uterine Cervical Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Head and Neck Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Anticoagulants

Vaccines

Immunomodulating Agents

Atezolizumab

Edetic Acid

Pentetic Acid

Monatide (IMS 3015)

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Induction phase:

* Atezolizumab 1200 mg intravenous (IV) every 3 weeks since day 1
* UCPVax (combined with Montanide ISA51 as adjuvant) at 1 mg subcutaneously in two separate sites (one site per peptide) at day 1, 8, 15, 29, 36 and 43 (induction phase).

Boost phase:

* UCPVax boosts vaccine every 6 weeks for the 2 first boosts (boost 1 and boost 2) and then every 9 weeks (boost 3 to boost 5)
* Atezolizumab 1200 mg IV every 3 weeks until disease progression or unacceptable toxicity until disease progression or unacceptable toxicity.

Four blood samples will be collected at:

* baseline
* 2 months from inclusion (+/- 1 week)
* 4 months from inclusion (+/- 1 week)
* the end of vaccination visit (+/- 1 week).

A total of 8 EDTA (ethylenediaminetetraacetic acid) tubes of 6 ml will be collected at each time point to perform:

PBMC collection: 6 EDTA tubes of 6 ml of peripheral blood mononuclear cell \[PBMC\] will be sent to the central laboratory (Biomonitoring Platform of Besançon, CHRU de Besançon located at Etablissement Français du Sang) at room temperature within 24 hours via an approved carrier for their processing, storage and immunomonitoring analysis. A sending sheet of the samples will be attached to each single sample.

Plasma collection: One 6 ml EDTA tube should be frozen in each investigation center for plasma collection.

Plasma for circulating tumoral DNA (ctDNA) collection: One 6 ml EDTA tube should be frozen in each investigation center for ctDNA collection.

Blood sample collection

A tumor biopsy will be realized and centralized at baseline and at 2 months. Collection of tumor biopsies will be guided by ultrasound or CT scan

Tumor biopsies

A CT scan will be planned

* at baseline
* at tumor evaluation visit (8 weeks)
* every 8 weeks (+/- 1 week)
* at end of treatment visit.

CT scan

Induction phase: Atezolizumab 1200 mg intravenous every 3 weeks since day 1

Boost phase: Atezolizumab 1200 mg intravenous every 3 weeks until disease progression or unacceptable toxicity until disease progression or unacceptable toxicity.

Induction phase: UCPVax (combined with Montanide ISA51 as adjuvant) at 1 mg subcutaneously in two separate sites (one site per peptide) at day 1, 8, 15, 29, 36 and 43 (induction phase).

Boost phase: UCPVax boosts vaccine every 6 weeks for the 2 first boosts (boost 1 and boost 2) and then every 9 weeks (boost 3 to boost 5).

UCPVax

Christophe BORG, Pr

70% all cases of cervical cancer, 95% of anal cancers and about 70% of oropharyngeal cancers are linked to Human Papillomavirus (HPV) infection. HPV oncogenic proteins are trans-activators of telomerase. Indeed, E6 oncoprotein transactivates the human telomerase (hTert). Our group has conducted a clinical trial (NCT02402842) in advanced squamous cell anal cancer (SCCA) and investigators have shown a correlation between the presence of anti-HPV immunity and anti-telomerase T helpher 1 (TH1) CD4 T cell responses, establishing telomerase as an appropriate antigen in HPV-related cancers.

Tumor-reactive CD4+ T cells have been found to ensure efficient effector Cytotoxic T Lymphocytes (CTL) recruitment at the tumor site. Promoting tumor specific TH1 CD4 activation might be an attractive therapeutic option to enhance anti-PD-1/PD-L1 (Programmed cell Death-1/Programmed cell Death-Ligand1) efficacy. However, no option is currently available to expand tumor specific TH1 lymphocytes in most patients. Then, investigators have identified four novel MHC (Major Histocompatibility Complex) class II-restricted peptides derived from human telomerase reverse transcriptase (TERT) referred as "Universal Cancer Peptides" (UCP). UCPVax is a therapeutic cancer vaccine developed by our team and composed of two separate peptides called UCP2 and UCP4 derived from telomerase. This UCPVax vaccine is currently evaluated in a multicenter phase I/II study in Non Small Lung Cancer (NSCLC) (NCT2818426) and seems to show to be safe and immunogenic.

PD-1/PD-L1 immune checkpoint is a relevant candidate target for immunotherapy in HPV+ cancers, based on the prominent role of PD-1 and its ligand PD-L1 in HPV-driven immune-evasion. There is a strong rational of using PD-1 therapy in HPV+ cancers, however anti-PD-1/PD-L1 treatment induces a limited number of long term responses in HPV disease. Combining anti-PD-1/PD-L1 therapy with an antitumor vaccine gains serious consideration in HPV+ cancers. Indeed, anti-cancer vaccines can induce tumor-specific T cells expansion and activation and therefore restore the cancer-immunity cycle in patients lacking pre-existing anti-tumor responses.

So investigators propose to determine the clinical interest and immunological efficacy of a treatment combining the CD4 helper T-inducer cancer vaccine (UCPVax) with atezolizumab in patients with HPV+ cancers by evaluation of the objective response rate at 4 months according to iRecist criteria.

Combination of UCPVax Vaccine and Atezolizumab for the Treatment of Human Papillomavirus Positive Cancers (VolATIL)

A Phase II Study Evaluating the Interest to Combine UCPVax a CD4 TH1-inducer Cancer Vaccine and Atezolizumab for the Treatment of Human PapillomaVirus Positive Cancers

The main objective of this clinical trial is to assess the efficacy of a strategy combining UCPVax and atezolizumab treatment in patients with HPV+ cancer by evaluation of the objective response rate at 4 months according to iRecist.

Delay from the date of inclusion to death from any cause

Delay from the date of inclusion to the disease progression or death from any cause whichever occurs first

Health related quality of life will be assessed using EORTC (European Organisation for Research and Treatment of Cancer) questionnaire

Toxicities graded according to NCI-CTCAE criteria version 5

Roche Pharma AG

National Cancer Institute, France

Centre Hospitalier Universitaire de Besancon

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

UCPVax is a therapeutic cancer vaccine composed of two peptides called UCP2 and UCP4 derived from telomerase combined with Montanide ISA 51 VG as adjuvant.

The two peptides UCP2 and UCP4 will be emulsified in Montanide ISA 51 and injected subcutaneously in separate sites (one site per peptide), at days 1, 8, 15, 29, 36 and 43 (priming phase) following by boost vaccination every 8 weeks for 12 months.

UCPVAx is a therapeutic vaccine based on the telomerase-derived UCP designed to induce strong TH1 CD4 T cell responses in cancer patients.

Three doses of UCPVax (0,25 mg, 0,5 mg and 1 mg) will be tested in this phase I/II study by using Continuous Reassessment Method (CRML) dose escalation design model.

The phase I is a dose escalation study designed to evaluate safety of use of UCPVax and to estimate its Maximum Tolerated Dose (MTD).

The phase II is a dose deescalation designed to evaluate the immunogenicity of UCPVax according to the dose level.

UCPVax study is a prospective multicenter phase I/II study: 54 patients with metastatic NSCLC will be enrolled in 5 centers in France.

A translational research program will be performed to better define the eligibility criteria and predictive biomarkers needed for randomized phase II and Phase III trials.

Universal Cancer Peptide-based Vaccination in Metastatic NSCLC

Anticancer Therapeutic Vaccination Using Telomerase-derives Universal Cancer Peptides in Metastatic Non Small Cell Lung Cancer : A Phase I/II Study

The following adverse events graded according to CTCAE v 4.03 will be classified as DLTs :

* Hematologic:

  * Grade 4 neutropenia (ANC \<0.5 x 109/L) lasting \>5 days;
  * Febrile neutropenia (defined as neutropenia ≥Grade 3 \[ANC \<1000 cells/mm3\] and a body temperature ≥38.5°C);
  * Grade ≥3 thrombocytopenia (\<50.0 - 25.0 x 109/L) with bleeding;
  * Grade 4 thrombocytopenia (\<25.0 x 109/L) \>5 days;
  * Grade 4 anemia (hemoglobin \<6.5 g/dL or 4.0 nmol/L);
* Non-hematologic:

  o Grade ≥3 toxicities, except for alopecia and those grade 3 events that respond to treatment (eg. grade 3 nausea, vomiting, diarrhea that responds to standard medical supportive care within 48 hours will not be considered a DLT).
* Immune system disorder:

  * Grade ≥2 allergic reaction (except for local reaction at the injection site : grade ≥ 3)
  * Grade ≥2 autoimmune disease (colitis, thyroidis...)
  * Grade ≥2 cytokine release syndrome (nausea, headache, tachycardia, hypotension, rash and shortness of breath)

Antigen-specific T cell responses measured using IFN-gamma ELISPOT.

Tumor response evaluated per RECIST v1.1.

delay from the date of inclusion to the disease progression (RECIST) or death from any cause whichever occurs first,

delay from the date of inclusion to death from any cause.

HrQoL will be assessed using EORTC QLQ-C30 and LC13 modules specific to lung cancer

Invectys

Blood and Lymph Conditions

Heart and Blood Diseases

Rare Diseases

Polycythemia Vera

Polycythemia

Thrombocytosis

Thrombocythemia, Essential

Hematologic Diseases

Bone Marrow Neoplasms

Hematologic Neoplasms

Bone Marrow Diseases

Myeloproliferative Disorders

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Essential Thrombocythemia

Chronic Myeloproliferative Disorders

Imetelstat

Motesanib diphosphate

Enzyme Inhibitors

Protein Kinase Inhibitors

Induction dosing of 9.4 mg/kg weekly, followed by intermittent maintenance dosing.

This is a phase II open-label study of single agent imetelstat in patients with essential thrombocytopenia or with polycythemia vera who have failed or are intolerant to at least one prior therapy, or who refuse standard therapy.

For patients with ET: To obtain a preliminary estimate of efficacy of imetelstat, as measured by best hematologic response within the first year of therapy in patients with ET who have failed or are intolerant to at least one prior therapy, or who have refused standard therapy.

For patients with PV: To obtain a preliminary estimate of efficacy of imetelstat, as measured by maintenance of Hct \< 45% in men and \< 42% in women (or pre-specified Hct count that is tolerable) without phlebotomy or myelosuppressive therapy within the first year of therapy in patients with PV who have failed or are intolerant to at least one prior therapy, or who have refused standard therapy.

Open Label Study to Evaluate the Activity of Imetelstat in Patients With Essential Thrombocythemia or Polycythemia Vera

A Phase II Trial to Evaluate the Activity of Imetelstat (GRN163L) in Patients With Essential Thrombocythemia or Polycythemia Vera Who Require Cytoreduction and Have Failed or Are Intolerant to Previous Therapy, or Who Refuse Standard Therapy

Primary objectives are as follows: ET patients - best hematologic response within the first year of therapy and PV patients - maintenance of Hct \< 45% in men and \< 42% in women (or pre-specified Hct count that is tolerable) without phlebotomy or myelosuppressive therapy within the first year of therapy. Secondary objectives, to determine the durability of hematologic response and to determine the rate of phlebotomy required within the first year of therapy.

The safety and tolerability of imtelstat will be assessed by the incidence, nature, relatedness and severity of adverse events, laboratory abnormalities and vital signs.

Geron Corporation

Sarcoma

Neoplasms, Connective and Soft Tissue

Soft Tissue Sarcoma

Soft tissue sarcomas (STSs) are a rare group of cancers that can arise in any 'soft' tissue but commonly involve muscles, fat and nerves. Even following surgery and radiotherapy over 50% of tumours will recur or spread and at present, there is no reliable test that allows doctors to predict in which patients this will occur.

DNA that is not inside cells (cell-free or cfDNA) is present in very small quantities circulating in blood. In cancer patients some of this cfDNA comes from cancer cells. Analysis of cancer-derived cfDNA in patients with other cancers has shown that the quantity and characteristics of cfDNA changes with stage of disease and treatment. The researchers plan to investigate the abundance and persistence of cancer-derived cfDNA in STS patients at various stages of disease to investigate the potential role of these characteristics as biomarkers.

Selection of the genetic characters to be tracked in the patients' cfDNA is an important consideration. An established hallmark of a cancer cell is the ability to undergo an unlimited number of cell divisions. In normal human cells protective structures on the ends of chromosomes called telomeres provide a mechanism to limit the number of times a healthy cell can divide. This limitation has to be overcome in cancer cells for a tumour to form. This occurs by the activation of one of two telomere maintenance mechanisms (TMM) - either an enzyme called Telomerase or a mechanism known as Alternative Lengthening of Telomeres (ALT). In many sarcomas the activation of either TMM is associated with genetic changes (mutations) in a small number of genes. As these mutations are not present in normal cells but mark an essential feature of cancer cells (and their capacity for unlimited cell division) they are likely to be reliable markers of the presence of STS cells.

The investigators plan to develop sensitive, quantitative assays to detect TMM associated mutations in tumour derived cfDNA in the blood of patients with STSs, and track these mutations overtime. They will establish the amount of cancer-derived cfDNA in STS patients at the time of surgery, and persistence of this cfDNA during follow up visits following tumour resection and in the events of local tumour recurrence or spread (metastatic disease). Once these basic parameters are established analysis will be broadened to include other genes that are commonly mutated in STSs with a view of identifying other genetic characteristics that may also aid identification of patients at high risk of recurrence or spread. In summary all of the assays described above should facilitate better monitoring of patients with STS, and allow earlier treatment if STS recurs following surgery.

Aims

The investigators plan a 2 year pilot observational study to:

* Identify and quantify circulating cell-fee DNA (cfDNA) in cases of Soft Tissue Sarcoma (STS)
* Investigate Telomere Maintenance Mechanisms (TMM) in STSs.
* Use TMM associated genetic mutations to identify and quantify tumour-derived cfDNA in STSs at time of tumour resection and throughout follow up
* Track the tumour derived cfDNA characteristics above over time and correlate with clinical outcome to identify potential STS biomarkers Hypotheses Based on findings in other cancers it is hypothesised that plasma cfDNA will be detectable in cases of STS. Given the key role telomere length maintenance plays in cancer cell development the investigators also hypothesise that TMM associated mutations will be present in tumour derived cfDNA, act as stable markers of STS tissue, and therefore increase in concentration as local recurrence or metastatic disease occurs.

Tumour derived cfDNA identification In months 0-3 sensitive assays to target known tumour-specific mutations will be developed. Using these on retrospectively collected tissues the investigators will verify that cfDNA can be detected (and quantified) in the plasma of patients with STSs.

Analysis of TMMs in STS tissue In months 3-12 tumour samples from every prospectively recruited sample will be analysed to establish which TMM is activated in STSs. Telomerase and ALT activity will each be assessed by published laboratory techniques.

Quantification and characterisation of TMM associated mutations / tumour derived cfDNA In months 10-12 quantitative Polymerase Chain Reaction based assays will be developed to identify the TMM associated mutations found to be most prevalent in STSs. In months 12-22 these assays will be used to identify and quantify these TMM associated mutations (and therefore also tumour-derived cfDNA) in the plasma samples taken from every prospectively recruited patient at time of surgery and throughout follow up.

Correlation of cfDNA characteristics with clinical outcome In months 22-24 cfDNA concentration, tumour-derived cfDNA concentration and the genetic characteristics of both will be correlated with clinical outcome measure including local recurrence, metastatic recurrence and death to determine these characteristics' potential as future biomarkers.

Patient recruitment / sample collection Patients will be recruited through the East Midlands Sarcoma Service. Samples already available will be collected from 2 sources to verify that cfDNA can be detected in STSs: Firstly 20 patients with metastatic disease will be asked to give consent for retrospective analysis of their tumour tissue already archived following histological analysis. One blood sample will also be collected from these patients for analysis. Secondly every STS sample already stored in the Nottingham Health Science Biobank, (Nottingham City Hospital) with an accompanying plasma sample also stored (15 at time of writing) will be analysed.

For the investigators remaining analysis between months 0-22 patients with non-metastatic high-grade STSs undergoing a planned resection locally will be approached to participate. 2013 figures suggest over 100 patients will be eligible for inclusion. Tumour tissue, blood, and unaffected muscle and saliva (2 sources of control DNA) will be collected at time of resection. Repeat blood samples will be collected 3 monthly until the end of recruitment.

Soft tissue sarcoma tissue Blood (Plasma and Buffy coat) Saliva

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Combination of UCPVax Vaccine and Atezolizumab for the Treatment of Human Papillomavirus Positive Cancers (VolATIL)	NCT03946358	Squamous Cell C... Anal Canal Canc... Cervical Cancer	Blood sample co... Tumor biopsies CT scan Atezolizumab UCPVax	18 Years - 75 Years	Centre Hospitalier Universitaire de Besancon
Combination of UCPVax Vaccine and Atezolizumab for the Treatment of Human Papillomavirus Positive Cancers (VolATIL)	NCT03946358	Squamous Cell C... Anal Canal Canc... Cervical Cancer	Blood sample co... Tumor biopsies CT scan Atezolizumab UCPVax	18 Years - 75 Years	Centre Hospitalier Universitaire de Besancon
Universal Cancer Peptide-based Vaccination in Metastatic NSCLC	NCT02818426	Metastatic Non-...	UCPVax	18 Years - 89 Years	Centre Hospitalier Universitaire de Besancon
Open Label Study to Evaluate the Activity of Imetelstat in Patients With Essential Thrombocythemia or Polycythemia Vera	NCT01243073	Essential Throm... Polycythemia Ve...	Imetelstat	18 Years -	Geron Corporation
Genetic and Telomere Characteristics of High of Grade Soft Tissue Sarcomas	NCT02547376	Soft Tissue Sar...		18 Years -	University Hospitals, Leicester

Spots Global Cancer Trial Database for telomerase

Every month we try and update this database with for telomerase cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for telomerase

Every month we try and update this database with for telomerase cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for telomerase cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.