Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Durvalumab

Immunoglobulins

Tremelimumab

Antineoplastic Agents, Immunological

Following systemic therapy, patients will undergo nephrectomy. Adjuvant therapy will be administered within 4-6 weeks of surgery. Subsequent follow-up will then be completed to assess adverse event resolution and long-term outcomes.

* Cohort 1: Durvalumab x 1 dose (n=6)
* Cohort 2: Durvalumab + Tremelimumab x 1 dose (n=6)
* Cohort 2a: Durvalumab + Tremelimumab x 1 dose (n=12)
* Cohort 3: Durvalumab + Tremelimumab x 1 dose (n=9)

Cohorts 1 and 2: Adjuvant dosing of Durvalumab x 1 beginning 2-8 weeks after surgery.

Cohort 2a: Durvalumab monotherapy until 1 year after nephrectomy.

Cohort 3: Adjuvant dosing of durvalumab + tremelimumab x 1 beginning 2-8 weeks after surgery, then durvalumab monotherapy until 1 year after nephrectomy.

Durvalumab is a programmed cell death ligand-1 monoclonal antibody which has demonstrated anti-tumor efficacy renal cell carcinoma and other malignancies via activation of the immune system.

Tremelimumab is a CTLA-4 monoclonal antibody.

Moshe Ornstein, MD, MA

The purpose of this study is to investigate the safety and feasibility of administering investigational drugs (meaning not Food and Drug Administration (FDA)-approved for kidney cancer) prior to surgical treatment for kidney cancer. The first drug is called MEDI4736, and the second drug is called tremelimumab. Both of these drugs work by attaching to certain proteins on immune cells with the goal of stimulating an immune response against cancer cells. This is a phase 1 trial, with the primary goal of identifying if this treatment is safe and possible side effects when given prior to surgery for kidney cancer.

Objectives:

Primary Objective

• To investigate the safety and feasibility of neoadjuvant plus adjuvant dosing of durvalumab +/- tremelimumab in patients with localized renal cell carcinoma (RCC).

Secondary Objectives

* To assess the immune response to neoadjuvant plus adjuvant dosing of durvalumab +/- tremelimumab in patients with localized RCC as measured an increased density of tumor-infiltrating CD8 T-cells.
* To assess the antitumor effect of neoadjuvant durvalumab +/- tremelimumab in patients with RCC as measured by change in tumor size.

Correlative Objectives

* To explore pharmacodynamic and microbiome markers of response to checkpoint inhibition in pre- and post-treatment blood and tissue samples (e.g. infiltration of T cells, T regulatory cells and/or Myeloid-derived suppressor cells).
* To understand changes in the immunological milieu mediated by pre-surgical immune checkpoint blockade (e.g. change in T cell repertoire, expression of T cell agonist targets).

Study Design:

This study will be a single-arm open-label phase Ib study of neoadjuvant durvalumab +/- tremelimumab in localized / locally advanced, non-metastatic RCC patients suitable for nephrectomy. Upon selection as appropriate for study, patients will undergo computed tomography (CT)-guided biopsy of renal mass to obtain histological confirmation of diagnosis, and immunologic characterization of the RCC tumor. Peripheral blood will also be drawn at time of screening. Patients will subsequently receive systemic neoadjuvant treatment in one of 5 cohorts as defined below. Following systemic therapy, patients will undergo nephrectomy. Type of surgery (open vs. minimally invasive, radical vs. partial) and template for lymph node dissection are at the discretion of surgeon. Timing of surgery in relation to adverse events and/or treatment for adverse events from neoadjuvant dosing of study drugs is at the discretion of the surgeon. Adjuvant therapy will be administered within 4-6 weeks of surgery. Subsequent follow-up will then be completed to assess adverse event resolution and long-term outcomes.

Neoadjuvant MEDI 4736 +/- Tremelimumab in Locally Advanced Renal Cell Carcinoma

A Phase Ib Trial of Neoadjuvant Durvalumab (MEDI4736) +/- Tremelimumab in Locally Advanced Renal Cell Carcinoma

Dose-limiting toxicities (DLTs) will be evaluated from the first dose of drug through the first adjuvant dose of durvalumab. Grading of DLTs will follow the guidelines provided in the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

* Grade 1

  * Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic, and radiological interventions
  * Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, analgetics, diuretics, electrolytes, and physiotherapy. This grade also includes wound infections opened at the bedside
* Grade II

  -- Requiring pharmacological treatment with drugs other than such allowed for grade I complications
* Blood transfusions and total parenteral nutrition are also included

  --Grade III - Requiring surgical, endoscopic or radiological intervention
* Grade IIIa - Intervention not under general anesthesia
* Grade IIIb - Intervention under anesthesia
* Grade IV - Life-threatening complication (including CNS complications) requiring IC/ICU management
* Grade IVa - Single organ dysfunction (including dialysis)
* Grade IVb - Multiorgan dysfunction
* Grade V - Death of a patients

The primary readout here will be increased CD8 infiltration versus a large historical control cohort already in our possession. Preliminary studies will focus on peri-tumoral and inter-tumoral CD8 infiltration, as those parameters are associated with responsiveness to immunotherapy in melanoma patients. Secondary efforts will focus on the induction of a pro-inflammatory infiltrate by comparing the surgical specimen to pre-treatment biopsies. Those assays will be challenged by the small amount of tissue generally available from biopsy, but are important since the biopsy could potentially serve as a valuable prediction tool to guide early treatment.

RECIST 1.1 Criteria Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.

Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Progressive Disease (PD): 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. (Note: the appearance of one or more new lesions is also considered progression).

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

o The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.

Moshe Ornstein

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Peripheral T-cell Lymphoma

Antirheumatic Agents

Anti-Inflammatory Agents

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Prednisone

Vincristine

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Tubulin Modulators

Antimitotic Agents

Lead-in period is 4 days. Patients take a single dose of Chidamide tablet, then off for 3 days before the first cycle begins. In the subsequent treatment cycles, Chidamide tablets are given orally on Day 1,4,8 and 11 of each cycle. Cyclophosphamide, adriacin and vincristine are given in intravenous infusion on Day 1. On Day 1 to 5, prednisone is given orally. Treatment cycles are repeated every 3 weeks .The combination therapy lasts for at most 6 cycles. Patients enter the single agent therapy if attained complete response after 6-cycle combination therapy. In this stage, patients take chidamide orally on Day 1, 4, 8 and 11 of each cycle.

In the lead-in period, patients take a single dose of Chidamide tablet on the first day and then off for 3 days before the first cycle begins. In the subsequent treatment cycles, Chidamide tablets are given orally on Day 1,4,8 and 11 of each cycle.

Chidamide

On Day 1, cyclophosphamide is given in a 20-minute intravenous (IV) infusion at 750 mg/m\^2 in 5 minutes after chidamide administration

cyclophosphamide

On Day 1, Adriacin is given in a 20-minute IV infusion at 50 mg/m\^2 soon after cyclophosphamide administration.

adriacin

On Day 1, vincristine is given in IV infusion at 1.4 mg/m\^2 after adriacin administration.

vincristine

On Day 1 to 5, prednisone is given orally at 100 mg once a day

prednisone

Yuankai Shi, MD

The purpose of this dose-escalation study is to assess the safety and tolerability of treatment with Chidamide in a range of doses combined with CHOP in fixed dose in patients with newly diagnosed peripheral T-cell lymphoma.

The purpose of this study is to assess the tolerability and safety include adverse events, vital signs, laboratory tests, etc., of a range of doses of chidamide combined with CHOP in peripheral T-cell lymphoma patients, and to determine the dose limit toxicity and the maximum tolerable dose.

Clinical Trial of Chidamide Combined With CHOP in Peripheral T-cell Lymphoma Patients

An Open-label, Multi-center, Phase Ib Clinical Trial of Chidamide Combined With CHOP in Newly Diagnosed Peripheral T-cell Lymphoma Patients

Chipscreen Biosciences, Ltd.

Gland and Hormone Related Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Sarcoma

Neoplasms, Connective and Soft Tissue

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Genital Neoplasms, Female

Endocrine System Diseases

Gonadal Disorders

Ovarian Cancer

Ovarian Epithelial Cancer

Soft Tissue Sarcoma

Trabectedin

Trabectedin will be administered intraveinously, on day 1 of each cycle, every three weeks, as appropriate for assigned dose level.

Durvalumab will be administered intraveinously, at fixed doses of 1120 mg (equivalent to 15 mg/kg), on day 2 of each cycle, every three weeks.

Dose Escalation : 3 doses of trabectedin given in combination with durvalumab (fixed dose) will be investigated.

A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.).

Expansion cohorts: Once the Maximum Tolerated Dose (MTD) has been defined, the expansion cohorts will be opened. All patients will be treated at the MTD of Trabectedin (as defined in the dose escalation part of the trial) given in association with Durvalumab with the same schedule as in the dose escalation part of the trial.

Combination of trabectedin with durvalumab

A phase Ib trial study of trabectedin when prescribed in combination with durvalumab in locally advanced/unresectable soft-tissue sarcoma and ovarian carcinomas.

This is a multicenter, prospective phase Ib trial based on a dose escalation study design (3+3 traditional design) assessing three dose levels of Trabectedin given with durvalumab, followed by two expansion cohorts once the MTD is established.

This is a multicenter, prospective open-labeled phase Ib trial based on a dose escalation study design (3+3 traditional design) assessing three dose levels of trabectedin when prescribed in combination with durvalumab followed by two expansion cohorts (Soft-tissue sarcomas and ovarian carcinomas) once the MTD is established

Trabectedin Combined With Durvalumab in Patients With Advanced Pretreated Soft-tissue Sarcomas and Ovarian Carcinomas.

Trabectedin Combined With Durvalumab (MEDI4736) in Patients With Advanced Pretreated Soft-tissue Sarcomas and Ovarian Carcinomas. A Phase Ib Study.

Identification of predictive signature in responders by sequencing tumor sample

AstraZeneca

PharmaMar

Institut Bergonié

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Pharmaceutical Solutions

Docetaxel

Lenograstim

Mitogens

Trametinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Participants will receive Trametinib once daily for 21 days of each cycle + Intravenous Docetaxel once every three weeks over at least a one-hour infusion + Filgrastim (growth factor) subcutaneous injection once daily for prophylactic use.

Biconvex film coated oral tablets for once daily use with unit dosage strength of 0.5mg and 2.0 mg for dose level of 2.0mg, 1.5mg, 1.0mg, and 0.5mg

Yellow or brownish yellow solution for injections with unit dosage strength of 20mg and 80 mg for intravenous infusion once every 3 weeks over at least one-hour infusion

Clear and colorless solution for once daily sub-cutaneous injection with unit dosage strength of 75 micrograms (mcg) for dose level of 50 mcg/meter\^2 or 75 mcg/body

Filgrastim

GSK Clinical Trials

The primary purpose of this study is to evaluate the safety and tolerability of the combination therapy of trametinib and docetaxel with growth factor support in Japanese subjects with Stage IV or a postoperative recurrence non-small cell lung cancer (NSCLC). This study data will be used for making decision for further Japanese development plan for NSCLC. Six evaluable subjects will be enrolled in a dose level to evaluate the safety and tolerability of the combination treatment. Dose-limiting toxicity will be assessed during the first 21 days of combination therapy.

Safety and Tolerability of Trametinib in Combination With Docetaxel in Japanese Subjects With Non-small Cell Lung Cancer

An Open-Label, Phase Ib Study to Assess the Safety and Tolerability of GSK1120212 in Combination With Docetaxel in Japanese Subjects With Non-small Cell Lung Cancer

Laboratory parameters include: hematology, clinical chemistry, coagulation tests and urinalysis tests.

Vital sing measurement include: temperature, systolic blood pressure, diastolic blood pressure, heart rate, and blood oxygen saturation (SpO2)

AEs will be collected from the time the first dose of study treatment is administered until 30 days following discontinuation of study treatment regardless of initiation of a new cancer therapy or transfer to hospice

PK parameters include: area under the concentration time curve over dosing interval (AUC\[0 to tau\]), maximum observed concentration (Cmax), time of occurence of Cmax (tmax), and pre-dose (trough) concentration at the end of the dosing interval

PK parameters include: area under the concentration time curve from time zero (pre-dose) extrapolated to infinite time (AUC\[0 to infinite\]), area under the concentration time curve from time zero to last quantifiable concentration within subject across all treatments (AUC\[0 to t\]), Cmax, tmax, systemic clearance of parent drug (CL), and volume of distribution (V)

As per RECIST v1.1 the response will be assessed from target lesion as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), not applicable (NA) or not evaluable (NE) and from non-target lesion as CR, Non-CR/Non-PD, NA or NE

GlaxoSmithKline

Gastrointestinal Agents

Lactitol

Spartalizumab

Immune Checkpoint Inhibitors

All subjects in all combination will be entered in one arm

PDR001

Novartis Pharmaceuticals

Caitlin Rogers

Catherine Shu

Ashley Drokin

Rom Leidner

Funda Meric-Bernstam

The purpose of this study is to continue to assess safety and tolerability, and to allow continued access to study treatment for subjects already receiving spartalizumab as single agent or in combination with other study treatments.

Rollover Study for Continued Safety and Tolerability in Subjects Treated With Spartalizumab Alone or in Combination With Other Study Treatments

An Open-label, Multi-center Rollover Protocol for Continued Characterization of Safety and Tolerability for Subjects Who Have Participated in a Novartis-sponsored Spartalizumab Study as Single Agent or in Combination With Other Study Treatments

Digestive System Diseases

Substance Related Disorders

Skin and Connective Tissue Diseases

Gastrointestinal Stromal Tumors

Drug-Related Side Effects and Adverse Reactions

Neoplasms, Connective Tissue

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Chemically-Induced Disorders

Amino Acids

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Tyrosine

This is a single-arm, two-cohort, open label phase Ib/II trial studying the combination of oral imatinib 400 mg, once daily, and oral selinexor given once weekly (Cohort A); and single-agent oral selinexor 60 mg BIW (Cohort B). The study will consist of:

* Cohort A: an initial escalation phase (Ib) evaluating increasing doses of selinexor in combination with fixed doses of imatinib administered in repeated 28-day cycles in advanced/metastatic, imatinib-resistant GIST patients, followed by en expansion phase (II) testing for safety and preliminary evidence of antitumor activity
* Cohort B: single-agent, fixed selinexor dose in the same target population

oral selinexor given once weekly (Cohort A), oral selinexor given BIW (Cohort B)

Selinexor

Imatinib

Cesar Serrano, MD

This is a single-arm, two cohort, open label phase I/II clinical trial studying the combination of oral imatinib 400 mg, once daily, and oral selinexor given once weekly (Cohort A); and single-agent oral selinexor 60 mg BIW (Cohort B). The study will consist of:

* Cohort A: an initial escalation phase (Ib) evaluating increasing doses of selinexor in combination with fixed doses of imatinib administered in repeated 28-day cycles in advanced/metastatic, imatinib-resistant GIST patients, followed by an expansion phase (II) testing for safety and preliminary evidence of antitumor activity
* Cohort B: single-agent, fixed selinexor dose in the same target population

Clinical Study Objectives:

Primary clinical study objective

Cohort A:

1.- To determine the maximum tolerated dose (MTD) and recommended phase II doses (RP2D) of selinexor in combination with imatinib among unresectable and/or metastatic GIST patients with prior failure to at least imatinib for advanced/metastatic disease.

Cohort B:

1. To evaluate the clinical benefit rate (CBR: CR+PR+SD ≥ 16 wks)

Secondary clinical study objectives (both cohorts A and B)

1. To evaluate the clinical benefit rate (CBR: CR+PR+ SD ≥ 16 wks)
2. To evaluate progression free survival (PFS)
3. To evaluate overall survival (OS)
4. To evaluate the objective response rate (ORR)
5. To evaluate the safety profile according to CTCAE 4.03
6. To compare PFS on selinexor and imatinib and on selinexor in monotherapy with PFS on last prior anti-cancer therapy.

Translational Study Objective - To explore the relationship between GIST genotype and CBR with selinexor and imatinib, and selinexor as single-agent

Pharmacokinetics Study Objective

- To measure the plasma concentration of imatinib and selinexor at limited timepoints specificed in schedule of assessment.

Phase Ib/II, single-arm, two-cohort, non-randomized, open-label, multicenter, national clinical trial, single agent, combinations products

Selinexor as Single Agent and With Imatinib in Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (SeliGIST)

A Multicenter, Phase Ib/II Trial of Selinexor as a Single Agent and in Combination With Imatinib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GISTs)

The final publication of the trial results will be written by the international coordinating investigators on the basis of the final analysis performed. The draft manuscript will be reviewed by the coordinating investigators and other co-authors. After revision the manuscript will be sent to a major scientific journal. Results obtained in the different strata may be separately published.

Maximum tolerated dose (MTD) is defined as the highest dose level with ≤1 out of 6 patients experiencing a dose limiting toxicity (DLT) during the first 28 days of treatment. Dose escalation cohort (Phase 1b) seeks to determine the frequency and characteristics of DLTs of the selinexor plus imatinib combination at each dose level during the first cycle of therapy. Phase Ib will be carried out in standard 3+3 format, based on the toxicities found during the first cycle of therapy.

Clinical benefit rate (CBR) is defined as CR+PR+SD ≥ 16 wks

Efficacy measured by PFS assessed by median time. PFS is defined as the time between the date of first experimental treatment dose and the date of disease progression (according to RECIST 1.1 criteria).

Efficacy measured by OS. OS is defined as the time between the date of first experimental treatment dose and the date of death due to any cause. OS will be censored on the last date a subject was known to be alive, or when the last enrolled patiens are followed up to for 12 months, whichever is early.

Efficacy measured by ORR. ORR is defined as the number of subjects with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable subjects (according to RECIST 1.1 and Choi criteria).

Safety profile of the experimental treatment, through assessment of adverse event type, incidence, severity, time of appearance, related causes, as well as physical explorations and laboratory tests. Number of participants with treatment-related adverse events as assessed by CTCAE v4.03.

Toxicity will be graded and tabulated by using CTCAE 4.03.

GIST genotype determinations and its correlation with response to the treatment with selinexor and imatinib in terms of clinical benefit (CBR).

To measure the plasma concentration of imatinib and selinexor at limited timepoints specificed in schedule of assessment.

Number of patient with CBR ≥ 30% lasting ≥ 16 weeks

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Neoadjuvant MEDI 4736 +/- Tremelimumab in Locally Advanced Renal Cell Carcinoma	NCT02762006	Renal Cell Carc... Kidney Cancer	Durvalumab Tremelimumab	18 Years -	Case Comprehensive Cancer Center
Clinical Trial of Chidamide Combined With CHOP in Peripheral T-cell Lymphoma Patients	NCT02809573	Peripheral T-ce...	Chidamide cyclophosphamid... adriacin vincristine prednisone	18 Years - 65 Years	Chipscreen Biosciences, Ltd.
Trabectedin Combined With Durvalumab in Patients With Advanced Pretreated Soft-tissue Sarcomas and Ovarian Carcinomas.	NCT03085225	Ovarian Carcino... Soft Tissue Sar...	Combination of ...	18 Years -	Institut Bergonié
Safety and Tolerability of Trametinib in Combination With Docetaxel in Japanese Subjects With Non-small Cell Lung Cancer	NCT01938456	Lung Cancer, No...	Trametinib Docetaxel Filgrastim	20 Years -	GlaxoSmithKline
Rollover Study for Continued Safety and Tolerability in Subjects Treated With Spartalizumab Alone or in Combination With Other Study Treatments	NCT04058756	Advanced Solid ...	PDR001	18 Years -	Novartis
Trabectedin Combined With Durvalumab in Patients With Advanced Pretreated Soft-tissue Sarcomas and Ovarian Carcinomas.	NCT03085225	Ovarian Carcino... Soft Tissue Sar...	Combination of ...	18 Years -	Institut Bergonié
Selinexor as Single Agent and With Imatinib in Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (SeliGIST)	NCT04138381	Maximum Tolerat... GIST Metastatic Adul... Drug Toxicity Drug Use	Selinexor Imatinib	18 Years -	Grupo Espanol de Investigacion en Sarcomas
Neoadjuvant MEDI 4736 +/- Tremelimumab in Locally Advanced Renal Cell Carcinoma	NCT02762006	Renal Cell Carc... Kidney Cancer	Durvalumab Tremelimumab	18 Years -	Case Comprehensive Cancer Center

Spots Global Cancer Trial Database for phase ib

Every month we try and update this database with for phase ib 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 phase ib

Every month we try and update this database with for phase ib 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 phase ib 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.