Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Micronutrients

Antineoplastic Agents

Vitamins

Androgens

Hormones

Ascorbic Acid

Methyltestosterone

Testosterone

Testosterone undecanoate

Testosterone enanthate

Testosterone 17 beta-cypionate

Estrogens, Conjugated (USP)

Estrogens

Hormone Antagonists

Antioxidants

Protective Agents

Trace Elements

Antineoplastic Agents, Hormonal

Anabolic Androgenic Steroids

Anabolic Agents

Vitamin C

Arm A (cMAB): ADT (LHRH agonist or antagonist) + ARPI (abiraterone or enzalutamide or apalutamide or darolutamide) continuously until start of a new anti-cancer therapy.

Arm B (iMAB): no further treatment, including ADT and ARPI; decision to restart ADT (LHRH agonist or antagonist) and the initial ARPI (abiraterone, enzalutamide, apalutamide or darolutamide) is left at Investigator discretion.

no treatment until significant PSA increase as per treating physician at which point patient restarts ADT (LHRH agonist or antagonist) + ARPI (abiraterone or enzalutamide or apalutamide or darolutamide). Once PSA \< 0.2 ng/mL, treatment stops again.

iMAB

LHRH agonist or antagonist + ARPI (abiraterone or enzalutamide or apalutamide or darolutamide)

cMAB

EORTC

Bertrand Tombal, Prof

Silke Gillessen, Prof

This study addresses the global topic of treatment optimization, i.e. achieving similar benefit while reducing the duration of treatment, hence hoping to decrease the burden of side-effects, improve quality-of life and reduce resource utilization.

The primary goal of de-escalation is to investigate whether using an intermittent regime results in a similar OS to continuous treatment.

Prostate cancer is known to be dependent on testicular and adrenal androgens and the earliest identified treatments were the suppression of the body's production of testosterone. Then came the development of drugs able to block the androgen receptors that multiplied on the cancer cell membranes. The combination of these drugs presently approved by the EMA for first line treatment of mHNPC are understood to be given maximum androgen blockage and to be used until progression. All have been shown to positively impact overall survival. For patients, however, the consequences of continuous intensified MAB, and thereby testosterone suppression, have impacted their quality of life, especially in the form of fatigue, emotional distress, decrease of libido and loss of sexual function. This is in addition to toxicities linked to the mechanisms of these drugs which include cardiovascular diseases, cognitive effects and loss of bone mineral density.

Treatment optimization is rarely addressed by clinical trials run for registration purposes. Toxicity is subsumed under efficacy and keeping the cancer at bay or controlled at any cost. Overall patient experience is not taken into account when determining what is an acceptable trade-off. Intermittent treatment or drug holiday are options to manage drug toxicities but longer off-treatment periods remain rare due to the fear of losing efficacy.

Prostate cancer is an ideal setting to study the benefits of intermittent treatment as PSA levels have been shown to be a good indicator of cancer status. By holding androgen blockade after good PSA response, patients get the opportunity of seeing an improvement in their quality of life as testosterone levels slowly recover. The longer a patient stays off treatment, the more improvements to his overall wellbeing can be felt. Monitoring PSA levels provides an early signal to cancer regrowth and allows for the restart of MAB when it becomes necessary.

While improving the patient's quality of life, there is as yet no indication as to the possible impact of this approach on overall survival. Alternating off/on treatment could delay both the start of the next line of treatment and the development of castration resistance but the absence of constant androgen suppression could also have the opposite effect and precipitate new alternatives to cancer cells testosterone dependence.

This trial will randomize patients to either continue with their treatment as prescribed or to stop treatment until PSA levels indicate the necessity of restarting suppression. The latter group can stop treatment again when PSA levels reaches 0.2 ng/mL or lower. There is a need to investigate whether the benefit to patient's lives of holding long-term treatment will outweigh the risks of shortening overall survival. This trial is being done to allow both patients and their treating teams to have the data needed to make an informed decision on the best treatment approach.

Intermittent Androgen Deprivation Therapy in the Era of AR Pathway Inhibitors

Intermittent Androgen Deprivation Therapy in the Era of AR Pathway Inhibitors; a Phase 3 Pragmatic Randomized Trial.

the overall survival (OS) at 3 years using an iMAB regimen is non-inferior to continuous treatment.

proportion of patients who do not restart within 1 year of interrupting their MAB therapy (given as part of the induction phase) is not less than 70%

Safety according to the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0 for toxicity and Serious Adverse Event reporting.

the overall time in months that the patient was on MAB treatment

the overall time in months until the patient began the next systemic prostate cancer therapy

The magnitude of change in HRQoL in terms of physical functioning from EORTC QLQ-C30

The magnitude of change in HRQoL in terms of sexual activity scale of EORTC QLQ PR25

The magnitude of change in HRQoL in terms of pain characteristics from the IL249 item list; To cover all important HRQoL domains and to have more granularity on some of the selected domains, additional HRQoL concepts are searched in the EORTC item library. This resulted in the inclusion of an additional scale that measures the pain characteristics.

The selected scale and corresponding items address the pain characteristics (the nature of the pain: constant versus intermittent and whether the pain can be relieved by pain medications)

The magnitude of change in HRQoL in terms of physical fatigue from the IL249 item list; To cover all important HRQoL domains and to have more granularity on some of the selected domains, additional HRQoL concepts are searched in the EORTC item library. This resulted in the inclusion of an additional scale that measures the physical fatigue.

The selected scale and corresponding items address the energy levels, exhaustion, sleepiness.

Health utility derived from patient reported QLQ-C30 data and patient demographics;Health utilities summarize a patient's overall health status, and this parameter can be applied in cost-effectiveness analyses. Published mapping algorithms can be used to calculate health utility based on the collected QLQ-C30 data, either directly or indirectly. The indirect algorithms first maps QLQ-C30 scores to European Quality-of-Life-5 Dimensions (EQ-5D) scores and then to health utility scores. The collected HRQoL data using QLQ-C30 will be mapped first to EQ-5D scores using an established mapping approach from the literature, and then further translated to health utility values for each study subject and at each assessment of HRQoL, taking into account published national value sets for this conversion.

Cancer Trials Ireland

UNICANCER

Spanish Oncology Genito-Urinary Group

European Organisation for Research and Treatment of Cancer - EORTC

Digestive System Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Hematinics

Irinotecan

Bevacizumab

Cetuximab

Leucovorin

Fluorouracil

Levoleucovorin

Oxaliplatin

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antidotes

Folic Acid

Vitamin B Complex

Folinic Acid

Folate

Vitamin B9

Patients in the FOLFOXIRI + Bmab group receive until 12 cycles of FOLFOXIRI plus bevacizumab, consisting of a 30-minute infusion of bevacizumab at a dose of 5 mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and bevacizumab every 14 days until disease progression.

Patients in the experimental group received until 12 cycles of FOLFOXIRI plus cetuximab, consisting of a 30-minute infusion of cetuximab first time at a dose of 400 mg per kilogram, after the second time at a dose of 250mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and cetuximab every 14 days until disease progression.

fluorouracil

irinotecan

oxaliplatin

bevacizumab

cetuximab

Masashi Fujii, MD

Sachika Koyama, Ms

Toshifusa Nakajima, MD

This study is to verify the advantage of FOLFOXIRI plus cetuximab over FOLFOXIRI plus bevacizumab as the first-line therapy in metastatic colorectal cancer patients with RAS wild-type tumors.

This study is to verify the advantage of FOLFOXIRI plus cetuximab over FOLFOXIRI plus bevacizumab as the first-line therapy in metastatic colorectal cancer patients with RAS wild-type tumors. In this study the investigators employed deepness of response as a primary endpoint.

A Study of FOLFOXIRI Plus Cetuximab vs. FOLFOXIRI Plus Bevacizumab

A Randomized Phase II Study to Investigate the Deepness of Response of FOLFOXIRI Plus Cetuximab (Erbitux) Versus FOLFOXIRI Plus Bevacizumab as the First-line Therapy in Metastatic Colorectal Cancer Patients With RAS Wild-type Tumors: DEEPER

The maximum tumor shrinkage rates by Response Evaluation Criteria in Solid Tumors (RECIST) throughout the treatments

The rates of tumor shrinkage by RECIST at 8 weeks

The tumor shrinkage rates by RECIST at 4 months

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Intermittent Androgen Deprivation Therapy in the Era of AR Pathway Inhibitors	NCT05974774	Prostate Cancer	iMAB cMAB	18 Years - 100 Years	European Organisation for Research and Treatment of Cancer - EORTC
A Study of FOLFOXIRI Plus Cetuximab vs. FOLFOXIRI Plus Bevacizumab	NCT02515734	Colorectal Canc...	fluorouracil Leucovorin irinotecan oxaliplatin bevacizumab cetuximab	20 Years -	Japan Clinical Cancer Research Organization

Spots Global Cancer Trial Database for cmab

Every month we try and update this database with for cmab 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 cmab

Every month we try and update this database with for cmab 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 cmab 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.