Neoplasms

All Conditions

Symptoms and General Pathology

Carcinoma

Adenoma

Polyps

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Herbal and Botanical

All Drugs and Chemicals

Cola

Group II standard colonoscope, no further device used

Endocuff Vision cap on Standard colonoscope

Endocuff group

Thomas Rösch

The aim of this study is to evaluate the effect of ENDOCUFF VISION® (caps with soft, about 1 cm long lateral feet of rubber ("Endocuff") to flatten the colon folds) on ADR in a real-life setting (general practices) and in a homogenous patient collective (screening colonoscopies only).

It is a prospective randomized multi centric study, with participation of at least 10 study sites (private practice). The study is an inverstigator-initiated trial (IIT).

Depending on the randomization (closed envelope), the patients are examined with the standard instruments without or with ENDOCUFF VISION®.

Group 1: screening colonoscopy with standard colonoscopes with ENDOCUFF VISION® Group 2: screening colonoscopy with standard colonoscopes without cap

Colonoscopy is currently the best method for the detection of colon carcinomas and, as precursor, adenomas, since these can also be biopsied and removed. Therefore, the screening colonoscopy was introduced at the end of 2002 (covered by state insurance) from the age of 55. The main quality parameter for outcome quality is the adenoma detection rate (ADR), which correlates with the rate of the carcinomas prevented. However, since even smaller polyps, especially if they are flat or sunken, may be relevant for colon cancer development, the aim of colonoscopy should be to be able to recognize and remove as many adenomas as possible. There is a need to optimize the efficiency of screening colonoscopy by increasing the rate of adenoma detection, as it is known from many studies that approximately 15-30% of adenomas can be missed- even though the adenoma rate in the German screening colonoscopy register continues to increase over the years and currently stands at 28%.

Previous studies on the increase of the adenoma detection rate by endoscopy concerning newer endoscope technologies including conventional caps have been almost entirely negative.

For about 2 years, a newer version of ENDOCUFF VISION® caps (caps with soft, about 1 cm long lateral feet of rubber (Endocuff) to flatten the colon folds) is available which has already been used in about 8,000 colonoscopies in Germany and another 10,000 colonoscopies in Europe; there are no studies on this version of Endocuff caps.

The aim of this study is to evaluate the effect of ENDOCUFF VISION® in a real-life setting (general practices) and in a homogenous patient collective (screening colonoscopies only).

It is a prospective randomized multi centric study, with participation of at least 10 study sites (private practice). The study is an inverstigator-initiated trial (IIT).

A new technique for ADR improvement within colonoscopy can only be tested in a comparative study in two groups comparing the adenoma rate between the two groups. An independent gold standard does not exist in this sense, but the confirmation by the endoscopically taken histology serves as gold standard for the diagnosis adenoma. The alternative of double examinations (tandem colonoscopy) in each patient is in the setting of private practice not feasible.

Depending on the randomization (closed envelope), the patients are examined with the standard instruments without or with ENDOCUFF VISION®.

Group 1: screening colonoscopy with standard colonoscopes with ENDOCUFF VISION® Group 2: screening colonoscopy with standard colonoscopes without cap

A Prospective Randomized Comparison of the Adenoma Detection Rate With a Disposable Cap (ENDOCUFF VISION®)

A Prospective Randomized Comparison of the Adenoma Detection Rate in Screening Colonoscopy With and Without a Disposable Cap (ENDOCUFF VISION®)

Differences in ADR with or without the new disposable ENDOCUFF VISION® cap. Hypothesis: Endocuff Vision improves the adenoma detection rate (ADR) by about 25% compared to the comparison group.

differences in adenoma subgroups (between intestinal folds with good accessibility, between intestinal folds with poor accessibility, on top of intestinal fold, behind intestinal fold )

measured by comparison with size of snare or forceps

loiw grade intraepithelial neoplasia (LGIN), high grade intraepithelial neoplasia (HGIN), sessile serrated Adenoma (SSA), Carcinoma

adjustability of adenoma by colonoscope on a score scale from 1(very good) - 6 (poor)

resection of adenoma by biopsy, polypectomy, resection by forceps, none

Norgine

Universitätsklinikum Hamburg-Eppendorf

Prof. Dr. med.

Digestive System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Colorectal Neoplasms

Endometrial Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Eligible subjects will receive study treatment of 50mg TPST-1495 taken orally, once a day for 7 days prior and discontinued 3 days prior to scheduled surgery.

TPST-1495

Lead Nurse

Susanna Ulahannan, MD

The proposed clinical trial with TPST-1495 can help people with two types of cancer, Endometrial Cancer (EC) and Colorectal Carcinoma (CRC), who need surgery. The investigator plans to evaluate how well TPST-1495 works against these cancers by checking blood samples and tumor tissues taken before and after the treatment to see if it is an effective treatment option to help the immune system fight against cancer.

TPST-1495, a dual antagonist targeting human prostaglandin E2 receptor subtypes EP2 and EP4, has shown promising safety and possesses potential immunomodulatory and antineoplastic properties in preclinical research. Based on previous clinical research, the investigator proposes that TPST-1495 treatment could offer anti-cancer benefits to endometrial cancer (EC) and colorectal cancer (CRC) patients.

This pilot window-of-opportunity study aims to assess the safety and biological effectiveness of administering 50mg TPST-1495 orally once daily for seven days, with discontinuation three days prior to surgical therapy, involving 10 evaluable patients, with five each from the EC and CRC groups, for a maximum total of 20 participants enrolled to ensure 10 evaluable patients.

This pilot window of opportunity study proposes to evaluate the safety and biological efficacy of 50mg TPST-1495 in patients with EC or CRC undergoing surgical therapy.

Pilot Window of Opportunity Trial (POET)

A Phase 2 Pilot Window of Opportunity Study of the EP2 and EP4 Receptors Inhibitor TPST-1495 in Patients With Endometrial Cancer or Colorectal Cancer Planning to Undergo Surgical Therapy

Blood samples from patients with EC and/or CRC will be assessed at screening(pre-dose) and post-surgery to evaluate the expression of EP2 and EP4 receptor biomarkers within the PGE2 signaling pathway, providing insights into impact of TPST-1495 on pharmacodynamic pathway changes.

Tumor samples from patient with EC and/or CRC will be assessed at screening (pre-dose) and post-surgery to evaluate the expression of EP2 and EP4 receptor biomarkers within the PGE2 signaling pathway, providing insights into impact of TPST-1495 on pharmacodynamic pathway changes.

Number and percentage of participants with EC and/or CRC will be reported for anti-tumor activity of TPST-1495's, based on the measurement involving mean or median values of circulatory immune cells in blood samples and tumor tissues at screening(pre-dose) and post-surgery.

Number and percentage of participants with EC and/or CRC will be assessed for biological efficacy of TPST-1495's, based on the measurement involving mean or median values of circulatory immune cells in blood samples and tumor tissues at screening (pre-dose) and post-surgery.

This measure involves comparing the mean or median values of pre-blood and post-blood samples to assess the dynamic changes in immune cell populations. Flow cytometry will be utilized to examine alterations in immune cell composition following treatment.

This outcome measure focuses on comparing the mean or median values of pre-blood and post-blood samples to evaluate dynamic changes in inflammatory cytokines and chemokines. Flow cytometry will be employed to assess variations in the levels of these important biomolecules in response to treatment.

It utilizes CTCAE v5.0 to systematically report and assess the incidence and the severity of potential adverse events that patients may experience during treatment, ensuring consistent and reliable safety assessment.

University of Oklahoma

Heart and Blood Diseases

Rare Diseases

Peripheral Arterial Disease

Peripheral Vascular Diseases

Neoplasm Metastasis

Chronic Limb-Threatening Ischemia

Ischemia

Atherosclerosis

Arteriosclerosis

Arterial Occlusive Diseases

Vascular Diseases

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Hematinics

Liver Extracts

All CLTI patients presenting with wound, ischemia, foot infection (WIfI) stage IV disease consecutively treated at one institution

All CRLM patients presenting with wound, ischemia, foot infection (WIfI) with stage IV disease consecutively treated at one institution

For chronic limb-threatening ischemia (CLTI) patients that represents one of the revascularisation methods (endovascular, open surgery, hybrid).

For the colorectal liver metastasis (CRLM) patients that represents liver resection with adjuvant chemo- or radiotherapy

For chronic limb-threatening ischemia (CLTI) patients revascularisation surgery; for colorectal liver metastasis (CRLM) patients metastatic liver surgery

Lazar Davidovic, MD PhD

Petar M Zlatanovic, MD

Colorectal cancer (CRC) and chronic limb-threatening ischemia (CLTI) are relatively frequent and potentially fatal diseases. However, studies that are comparing clinical outcomes between CRC and CLTI patients in more advanced stages of the disease are lacking. The study aim was to evaluate outcomes of patients with colorectal cancer liver metastases (CRLM) treated by curative-intent liver resection and CLTI patients according to wound, ischemia, foot infection (WIfI) classification by comparing the short- and long-term clinical outcomes.

Peripheral arterial disease (PAD) is characterized by a global pandemic of growing proportions. In 2016, The Global Burden of Disease study reported that 202 million adults worldwide have PAD, with a higher prevalence compared to ischaemic heart disease (154 million), Alzheimer's disease (64 million) and cancer (43 million). The patient prognosis after PAD occurrence is poor because the disease often progresses to chronic limb-threatening ischemia (CLTI) that is an end-stage disease.

The 5-year mortality risk in CLTI patients is about 60%. When the mortality risk of CLTI is compared to mortality rates of the most common malignant diseases only six of them have a higher 5-year mortality rate compared to CLTI. One of them is colorectal cancer (CRC). CRC is the third most commonly occurring cancer in men and the second most commonly occurring cancer in women.

According to the latest CLTI treatment guidelines, the Society for Vascular Surgery (SVS) WIfI (wound, infection, ischemia) classification should be employed to stage limb condition in patients with CLTI that is analog to the use of tumor, nodes, metastases (TNM) cancer staging system. Recent data indicate that WIfI appears to correlate strongly with important clinical outcomes.

The annual incidence of CLTI is greater than the incidence of cancers characterized by high mortality rates (esophageal, stomach, brain and ovarian). In addition, more people die from CLTI each year compared to death rates of the already mentioned cancers. However, studies that are comparing clinical outcomes between cancer and CLTI patients in more advanced stages of the disease are lacking.

The study aim was to evaluate outcomes of the wound, ischemia, foot infection (WIfI) stage IV CLTI and colorectal cancer liver metastases (CRLM) patients managed by curative-intent liver resection by comparing the short- and long-term clinical outcomes.

Comparison of Outcomes of Patients With Stage IV Chronic Limb-threatening Ischemia and Colorectal Cancer

Comparison of Short- and Long Term Clinical Outcomes of Patients With Stage IV Chronic Limb-threatening Ischemia and Colorectal Cancer Liver Metastases

It will be made upon the reader's request

Number of participants who died from all causes of death in both chronic limb-threatening ischemia (CLTI) and colorectal liver metastasis (CLRM) population in a given time period

Number of participants for both chronic limb-threatening ischemia (CLTI) and colorectal liver metastasis (CLRM) population who died in hospital, as well as 30 days after the initial surgery

Number of participants with the following postoperative adverse events: cardiac (acute coronary syndrome, heart failure, pulmonary embolism), pulmonary (intubation lasting longer than 72h, pneumonia, atelectasis requiring active treatment), hemodialysis, wound infection, postoperative surgical bleeding, red blood cell transfusion rate, hepatic insufficiency, biliary fistula, major amputation.

Clinical Centre of Serbia

Principal Investigator

Adenocarcinoma

Disease Progression

Colonic Neoplasms

Micronutrients

Antineoplastic Agents

Anticoagulants

Coagulants

Fibrinolytic Agents

Leucovorin

Fluorouracil

Thromboplastin

Protein C

recombinant nematode anticoagulant protein c2 (rNAPc2)

Ted Love, MD

This is a multicenter, two-stage trial with the goal of evaluating up to 100 subjects. This trial will be performed to initiate identification of a safe and effective dose of twice-weekly, subcutaneous rNAPc2 for the second-line treatment of metastatic colorectal carcinoma in combination with contemporary 5-FU-based chemotherapy.

Cytotoxic chemotherapy combining 5-fluorouracil and leucovorin with irinotecan (FOLFIRI) or oxaliplatin (FOLFOX) or, more recently, treatment with XELOX (Roche) (capecitabine + oxaliplatin) has been the main approach for the treatment of metastatic colorectal carcinoma (mCRC), but with the advent of targeted therapies, biologic treatments are becoming an area of intense interest. Tissue factor (TF) is a transmembrane glycoprotein expressed by upwards of 85% of mCRCs.

Safety Study of Recombinant NAPc2 to Prevent Tumor Progression and Metastases in Metastatic Colon Cancer

Multicenter, Two-Stage Study to Evaluate the Safety and Efficacy of Second-Line Metastatic Colorectal Carcinoma Treatment With Recombinant NAPc2

ARCA Biopharma, Inc.

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Prostatic Neoplasms

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Pharmaceutical Solutions

Docetaxel

Dexamethasone

Abiraterone Acetate

Prednisone

Immunomodulating Agents

Durvalumab

Dexamethasone acetate

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Enzyme Inhibitors

Hormones

Hormone Antagonists

Cytochrome P-450 Enzyme Inhibitors

AZD4635 monotherapy as nanoparticle suspension 125 mg BID

AZD4635 monotherapy as nanoparticle suspension 75 mg QD

AZD4635 monotherapy as nanoparticle suspension 100 mg QD

AZD4635 as nanoparticle suspension 75 mg QD plus durvalumab

AZD4635 as nanoparticle suspension 100 mg QD plus durvalumab

AZD4635 as nanoparticle suspension plus enzalutamide

AZD4635 as nanoparticle suspension plus abiraterone acetate

AZD4635 as nanoparticle suspension plus durvaluamb in patients post immunotherapy with non-small cell lung cancer. Patients will be allocated randomly (1:1) between Arms F and G.

AZD4635 monotherapy as nanoparticle suspension in patients post immunotherapy with non-small cell lung cancer. Patients will be allocated randomly (1:1) between Arms F and G.

AZD4635 monotherapy as nanoparticle suspension in patients post immunotherapy with other solid tumours.

AZD4635 as nanoparticle suspension plus durvalumab in immunotherapy naïve patients with metastatic castration resistant prostate cancer. Patients will be allocated randomly (1:1) between Arms I and J.

AZD4635 monotherapy as nanoparticle suspension in immunotherapy naïve patients with metastatic castration resistant prostate cancer. Patients will be allocated randomly (1:1) between Arms I and J.

AZD4635 monotherapy as nanoparticle suspension in immunotherapy naïve patients with colorectal carcinoma.

AZD4635 as nanoparticle suspension plus durvalumab in immunotherapy-naïve patients with colorectal carcinoma.

AZD4635 monotherapy as nanoparticle suspension in immunotherapy naïve patients with other solid tumours.

AZD4635 capsule formulation monotherapy 75 mg, 150 mg, and 200 mg QD. A lower dose of 125 mg or 100 mg may be given. The pharmacokinetics of the single dose AZD4635 capsule formulation will be characterized on Cycle 1 Day 1 in Arm CA. Steady-state pharmacokinetics will be assessed on Cycle 1 Day 15. Cycle 1 and Cycle 2 will be administered in 3-week cycles to assess the safety and dose-limiting toxicity (DLT). After Cycle 1, PKs will be collected on Day 1 of every even numbered cycle (Cycles 2, 4, and 6).

AZD4635 capsule formulation 50 mg QD or 75 mg QD plus durvalumab and oleclumab. The pharmacokinetics of AZD4635 capsule formulation will be characterized on Cycle 1, 2, and 4 (Day 1) in Arm CB. Steady-state pharmacokinetics will be assessed on Cycle 2 Day 15. Cycle 1 will be administered in a 3-week cycle to assess the safety and dose-limiting toxicity (DLT). PKs will also be collected on Day 1 of Cycles 3 and 5.

AZD4635 capsule formulation 50 mg QD or 75 mg QD plus docetaxel. The pharmacokinetics of the single dose AZD4635 capsule formulation will be characterized on Cycle 1 Day 1 in Arm CC. Steady-state pharmacokinetics will be assessed on Cycle 1 Day 15. Cycles will be administered in 3-week cycles to assess the safety and dose-limiting toxicity (DLT). After Cycle 1, PKs will be collected on Day 1 of every even numbered cycle (Cycles 2, 4, and 6).

AZD4635 will be administered orally as a nanosuspension or capsule on a continuous schedule in Arms A, B, C, D, E, F, G, H, I, J, K, KD, L, AA, and EA. The AZD4635 nanoparticle drug product will be constituted extemporaneously as an oral suspension by the patient immediately prior to dosing. In Arms CA, CB, and CC AZD4635 will be administered as 75 mg or 50 mg capsules. Additionally, in Arm CA, AZD4635 will also be administered at 150 mg and 200 mg, or a lower dose of 125 mg or 100 mg may be given.

AZD4635

Durvalumab will be administered by intravenous infusion once every 4 weeks. Durvalumab should be reconstituted using aseptic techniques with sterile water for injection. The reconstituted solution will be diluted with 0.9% (w/v) saline prior to IV infusion.

Abiraterone acetate 1000 mg PO QD will be given with prednisone BID. The patient must receive abiraterone/prednisone according to the prescribing information during the DLT assessment period, Cycle 1 and Cycle 2. After Cycle 2 necessary abiraterone/ prednisone dose modifications may follow institutional standard practice.

Abiraterone acetate is supplied in 250 mg tablets.

Enzalutamide 160 mg PO QD will be dosed per the approved package insert. The patient must receive enzalutamide according to the prescribing information during the DLT assessment period, Cycle 1 and Cycle 2. After Cycle 2 necessary enzalutamide dose modifications may follow institutional standard practice.

Enzalutamide is supplied as 40 mg soft gelatin capsules.

Enzalutamide

Oleclumab 1500 mg will be given by IV infusion on Days 1 and 15 of each cycle.

Oleclumab

Patients in Cohort CC will receive docetaxel 75 mg/m² by IV infusion according to institutional standards of practice on Day 1 of each treatment cycle. If a patient's body surface area is greater than 2.2 m², the docetaxel dose will be adjusted to a body surface area of 2.2 m².

The patient should be pre-medicated with oral dexamethasone 8 mg (or equivalent) twice daily starting the day prior to treatment for a total of 3 days, or according to institutional standards of practice.

Johanna Bendell, MD

This is a Phase 1, open-label, multicenter study of continuous oral dosing of AZD4635 administered to patients with advanced solid malignancies. Dosing will be escalated until a maximum-tolerated dose (MTD) is determined in patients. The MTD will be defined by dose-limiting toxicity. The study design allows an escalation of dose with intensive safety monitoring to ensure the safety of the patients. Expansion cohorts will further assess safety and preliminary anti-tumor activity in a variety of advanced solid tumor malignancies. Other dosing schedules and/or combinations may be evaluated based on the emerging PK and safety data.

The primary objectives of this study are to:

* Investigate the safety and tolerability of AZD4635 monotherapy when given orally (PO) to patients with advanced solid malignancies.
* Investigate the safety, tolerability, and pharmacokinetics (PK) of AZD4635 monotherapy capsule formulation when given to patients with advanced solid malignancies.
* Investigate the safety and tolerability of AZD4635 PO when given in combination with durvalumab, durvalumab plus oleclumab, or docetaxel to patients with advanced solid malignancies and to investigate the safety and tolerability of AZD4635 in combination with abiraterone acetate or enzalutamide in patients with mCRPC.
* Define the maximum-tolerated dose (MTD) of AZD4635 in combination with durvalumab.
* Define the recommended Phase 2 dose (RP2D) of AZD4635 in combination with abiraterone acetate or enzalutamide.
* Determine the safety, tolerability, and immune effects of AZD4635 when administered in combination with durvalumab to patients with non-small cell lung cancer (NSCLC) who have previously received immunotherapy (Phase 1b portion).
* Investigate the safety and tolerability of AZD4635 capsule formulation in combination with durvalumab and oleclumab when given to patients with mCRPC or advanced solid tumor malignancy.
* Define the RP2D of AZD4635 capsule formulation in combination with durvalumab and oleclumab when given to patients with mCRPC or advanced solid tumor malignancy.
* Investigate the safety and tolerability of AZD4635 capsule formulation in combination with docetaxel when given to patients with mCRPC or advanced solid tumor malignancy.
* Define the RP2D of AZD4635 capsule formulation in combination with docetaxel when given to patients with mCRPC or advanced solid tumor malignancy.

The study will be conducted in two segments. The first segment of the study, designated Phase 1a, will be a dose escalation design in order to assess the safety, tolerability, pharmacokinetics (PK), and preliminary anti-tumor activity of ascending doses of AZD4635 as monotherapy, in combination with durvalumab or durvalumab plus oleclumab, in combination with docetaxel, and in combination with either abiraterone acetate or with enzalutamide.

A capsule formulation of AZD4635 will be evaluated in 3 arms (arms CA, CB, and CC). An oral nanoparticle suspension in water constituted extemporaneously by the patient will be administered in all other treatment arms. Most patients who started therapy with the nanoparticle suspension will transition to the capsule dosage form depending on the arm they are assigned to and emerging data. Active patients in arms C, D, E, F, G, H, I, J, K, KD, and L should be offered the option to transition to the capsule formulation at the discretion of the Investigator in discussion with the Medical Monitor. Patients in study arms AA and AE receiving AZD4635 as the nanoparticle suspension should change over to the capsule formulation as soon as possible at the discretion of the Investigator.

The dose escalation arms are described as follows:

* Arms A, B, and C (dose escalation of AZD4635 monotherapy).
* Arms CA, CB, and CC. In arm CA, the safety, tolerability and PK of the capsule formulation will be assessed in approximately 6 patients with advanced solid malignancies to ensure at least 5 patients have evaluable pharmacokinetic sampling. An additional 12 patients will be enrolled in this arm. Arm CB will assess the safety and tolerability and determine the RP2D of the AZD4635 capsule plus durvalumab and oleclumab in approximately 12 patients. Arm CC will assess the safety, tolerability and determine the RP2D of AZD4635 capsule plus docetaxel in approximately 12 patients .
* Arms D and E \[dose escalation of AZD4635 in combination with durvalumab anti-programmed death-ligand 1 (PD-L1)\].

Arms A through E enrolled 38 patients in Phase 1a in order to establish the Recommended Phase 2 Dose (RP2D) of the nanoparticle suspension formulation of AZD4635 as a single agent or in combination with durvalumab.

● Arms EA and AA. Arms EA and AA \[dose escalation of AZD4635 in combination with either abiraterone acetate plus prednisone or enzalutamide in patients with metastatic castrate-resistant prostate cancer (mRCPC)\]. The AZD4635 plus hormonal therapy cohorts will enroll concurrently. Patients who previously received abiraterone acetate, enzalutamide, or apalutamide as part of their prior treatments for mCRPC may be enrolled to the enzalutamide plus AZD4635 arm (Cohort EA) or the abiraterone acetate plus AZD4635 arm (Cohort AA) at the discretion of the Investigator. Approximately 24 to 48 patients with mCRPC will be treated in the AZD4635 plus hormonal therapy arms in order to establish the RP2D.

In Phase 1a approximately 90-132 patients will be treated with AZD4635 as a single agent or in combination with durvalumab, durvalumab plus oleclumab, docetaxel, abiraterone acetate or enzalutamide.

The second segment of the study, designated Phase 1b, will further assess the safety and preliminary activity in the expansion arms described below.

* Arm F - AZD4635 in combination with durvalumab. Post-immunotherapy non-small cell lung cancer (NSCLC). \[15 patients\]
* Arm G - AZD4635 monotherapy. Post-immunotherapy NSCLC. \[15 patients\]
* Arm H - AZD4635 monotherapy. Immune checkpoint resistant malignancies, previously treated with approved immunotherapy and progressed or responded and then stopped responding (e.g. renal cell carcinoma, head and neck carcinoma, or MSI high cancers which have approved settings for anti-PD-1 treatment).\[20 patients\]
* Arm I - AZD4635 in combination with durvalumab. Immune checkpoint naïve mCRPC.\[40 patients\]
* Arm J - AZD4635 monotherapy. Immune checkpoint naïve CRPC. \[40 patients\]
* Arm K - AZD4635 monotherapy. Immune checkpoint naïve colorectal carcinoma (CRC). CRC, excluding MSI high, which has not been treated with immune checkpoint inhibitors. \[20 patients\]
* Arm KD - AZD4635 in combination with durvalumab. Immune checkpoint naïve CRC. CRC, excluding MSI high, which has not been treated with immune checkpoint inhibitors. \[20 patients\]
* Arm L - AZD4635 monotherapy. Other solid tumours immune checkpoint naïve. Relapsed/refractory tumors which have not been treated with immune checkpoint inhibitors. \[20 patients\]

Patients will be randomly assigned between open-label arms with AZD4635 monotherapy and AZD4635 combined with durvalumab in NSCLC (Arms F/G) and mCRPC (Arms I/J) in order to minimize bias.

Patients with CRC, excluding MSI high, will be enrolled to AZD4635 monotherapy (Arm K) and AZD4635 combined with durvalumab (Arm KD) in patients with CRC.

Some arms will have a mandatory biopsy subgroup to ensure sufficient tissue is collected to assess the mechanism of action in tissue without excluding patients with nonbiopsiable disease. Biopsies are optional in all other arms.

A Phase 1 Clinical Study of AZD4635 in Patients With Advanced Solid Malignancies

A Phase 1, Open-Label, Multicenter Study to Assess Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-Tumor Activity of Ascending Doses of AZD4635 Both as Monotherapy and in Combination in Patients With Advanced Solid Malignancies

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

A Bayesian Logistic Regression Model (BLRM) based approach will be used to identify the set of AZD4635 doses where the incidence of DLTs is no larger than 33%. In each arm, up to 3 patients will be initially assessed. The dose will be escalated to the next higher dose level if all 3 patients in the previous dose level complete the DLT evaluation period without a DLT. Following the first DLT, the BLRM model will be run and the output made available to the safety review committee (SRC) to guide further dosing decisions. Each dose cohort will include a maximum of 6 patients.

The starting dose of AZD4635 is 50 mg PO QD. Escalations of AZD4635 will be made based on emerging data, including nonclinical or clinical evidence, and assessment by the Safety Review Committee (SRC). Each dose cohort will include a maximum of 6 evaluable patients. An additional 6 patients will be treated at selected dose(s) to obtain further the safety, tolerability, and PK.

Safety and tolerability will be assessed in monotherapy and combination cohorts by determining the incidence of adverse events, including abnormal laboratory results, physical examination findings, vital signs, and urinalysis.

The plasma concentration of AZD4635 will be determined by inspection of the concentration-time profile. Intensive pharmacokinetic sampling with matched ECGs is required in Phase 1a and in NSCLC Cohorts and mCRPC Cohorts in the monotherapy portion of the study. After the pharmacokinetic profile has been sufficiently characterised, sample collection in the mCRPC and NSCLC expansion cohorts may be limited to coincide with ECG-matched time points in patients being newly enrolled. Sparse sample collections are required from patients in CRC, Post-IO Other, and IO-Naïve Other cohorts.

The amount of AZD4635 (and metabolites) in urine will be determined in all patients. Pooled collections of urine 0 to 4 hours post dose, 4 to 8 hours post dose, and 8 to 24 hours post dose. Patients will collect all urine at home and bring the 8 to 24 hour pooled collection to the clinic. The total volume of each pooled sample will be recorded after which a 10 mL aliquot will be taken for analysis.

Plasma concentration of durvalumab and anti-drug antibody will be determined by inspection of the concentration-time profile. The date and time of collection of each sample will be recorded.

Twelve-lead ECGs will be obtained after the patient has been resting supine for at least 10 minutes. For each time point 3 ECG recordings should be taken at about 2- to 5 minute intervals.

Categorization of objective tumour response assessment will be based on the RECIST Version 1.1 guidelines for response (CR (complete response), PR (partial response), SD (stable disease), and PD (progressive disease).

For patients who only have non-measurable disease at baseline, categorization of objective tumour response assessment will be based on the RECIST Version 1.1 guideline for response for non-target lesions (NTLs): CR, PD, and Non CR/Non PD.

Progression free survival is defined as the time interval from the first dose of AZD4635 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from study treatment. Subjects who have not progressed or died at the time of analysis will be censored at the time of the last evaluable RECIST assessment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Prospective Randomized Comparison of the Adenoma Detection Rate With a Disposable Cap (ENDOCUFF VISION®)	NCT03442738	Adenoma Detecti...	Endocuff group	55 Years -	Universitätsklinikum Hamburg-Eppendorf
A Prospective Randomized Comparison of the Adenoma Detection Rate With a Disposable Cap (ENDOCUFF VISION®)	NCT03442738	Adenoma Detecti...	Endocuff group	55 Years -	Universitätsklinikum Hamburg-Eppendorf
Pilot Window of Opportunity Trial (POET)	NCT06129604	Colorectal Carc... Endometrial Car...	TPST-1495	18 Years -	University of Oklahoma
Pilot Window of Opportunity Trial (POET)	NCT06129604	Colorectal Carc... Endometrial Car...	TPST-1495	18 Years -	University of Oklahoma
Pilot Window of Opportunity Trial (POET)	NCT06129604	Colorectal Carc... Endometrial Car...	TPST-1495	18 Years -	University of Oklahoma
Comparison of Outcomes of Patients With Stage IV Chronic Limb-threatening Ischemia and Colorectal Cancer	NCT05116696	Chronic Limb-Th... Colorectal Carc... Colorectal Carc...	For chronic lim...	-	Clinical Centre of Serbia
Safety Study of Recombinant NAPc2 to Prevent Tumor Progression and Metastases in Metastatic Colon Cancer	NCT00443573	Colon Cancer	recombinant nem...	18 Years - 75 Years	ARCA Biopharma, Inc.
A Phase 1 Clinical Study of AZD4635 in Patients With Advanced Solid Malignancies	NCT02740985	Advanced Solid ... Non-Small Cell ... Metastatic Cast... Colorectal Carc...	AZD4635 Durvalumab Abiraterone Ace... Enzalutamide Oleclumab Docetaxel	18 Years - 130 Years	AstraZeneca
A Prospective Randomized Comparison of the Adenoma Detection Rate With a Disposable Cap (ENDOCUFF VISION®)	NCT03442738	Adenoma Detecti...	Endocuff group	55 Years -	Universitätsklinikum Hamburg-Eppendorf

Spots Global Cancer Trial Database for colorectal carcinoma (crc)