Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Fluorouracil

Capecitabine

Tislelizumab

Cisplatin

Immunomodulating Agents

Immune Checkpoint Inhibitors

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

This treatment group will be receive radiotherapy on the basis of standard first-line treatment, after all planned cycles of chemotherapy combined with PD-1 inhibitor completed.

This treatment group will be receive salvage radiotherapy on the basis of standard first-line treatment, when disease progressed and salvage radiotherapy is recommended by multidisciplinary team.

A maximum of six cycles was recommended for chemotherapy.

* Fluoropyrimidine (fluorouracil or capecitabine) with carboplatin or cisplatin;
* Paclitaxel (or Albumin-bound paclitaxel) with carboplatin or cisplatin.

TP (Paclitaxel with cisplatin or carboplatin) or PF (Fluoropyrimidine with cisplatin or carboplatin) regimen depended on investigator's choice.

Nivolumab or Pebolizumab or Tislelizumab or Serplulimab or Toripalimab or Sintilimab or Camrelizumab

PD-1 inhibitor

IMRT/VMAT technique. Patients receive radiotherapy once daily, 5 days a week for an average of 5 weeks. Radiotherapy is delivered to achieve a dosage of 49.22Gy/23f or 50Gy/25f to PGTV for lymphnode metastasis only patients and 40.66Gy/19f or 40Gy/20f for organ metastasis patients. Radiation treatment is planned after chemotherapy completed.

Consolidation Radiation

IMRT/VMAT technique. Patients receive radiotherapy once daily, 5 days a week for an average of 5 weeks. Radiotherapy is delivered to achieve a dosage of 49.22Gy/23f or 50Gy/25f to PGTV for lymphnode metastasis only patients and 40.66Gy/19f or 40Gy/20f for organ metastasis patients. Radiation treatment is planned after disease progression when recommended by multidisciplinary team.

Salvage Radiation

Wen-Yang Liu, MD

Wen-Yang Liu

Zhi-Hao Lu, MD

The treatment efficacy for stage IVb esophageal cancer has been improved through chemotherapy combined with immunotherapy recently.

On this basis, the investigators intend to conduct a prospective, multicenter phase II clinical trial to assess whether radiotherapy could further improve the survival of patients with metastatic esophageal cancer responding to PD-1 Inhibitor plus chemotherapy.

Accompanied tissue samples, blood samples and urine samples will be analyzed by molecular biological detection (Including Whole Exome Sequencing and proteomics) to explore potential biomarkers for predicting outcomes, efficacy and toxicity.

Esophageal cancer (EC) is one of the most common carcinomas with high morbidity and mortality worldwide. More than 30% of the patients were stage IV when diagnosed. Fluoropyrimidine plus platinum-based chemotherapy is recommended as first-line treatment for patients with metastatic EC for approximately four decades, however, only minimal improvement has been reached in overall survival (OS).

Recently, immune checkpoint inhibitors have shown effective antitumor activity in patients with unresectable, advanced or metastatic EC. Several randomized trials have demonstrated the PD-1 inhibitor could further improve the OS in patients with advanced esophageal squamous cell carcinoma (ESCC) on the basis of chemotherapy. Chemotherapy combined with immunotherapy has become one of the the standard treatment modality for metastatic EC.

As reported, for the patients with metastatic lung cancer or EC, locoregional radiotherapy could improve survival, especially in those who responding to systemic therapy. However, high-level evidence is still needed to assess whether these patients can benefit from local radiotherapy.

The efficacy of immunotherapy combined with chemotherapy is obviously better than that of chemotherapy alone. On this basis, locoregional radiotherapy may help those patients with metastatic EC responding to systemic therapy improve local control, relieve the local symptoms, and even improve survival.

Therefore, the investigators intend to conduct a prospective, multicenter phase II trial to assess the efficiency and safety of radiotherapy with chemotherapy and immunotherapy for patients with metastatic EC. Accompanied tissue samples, blood samples and urine samples will be analyzed by molecular biological detection to explore potential biomarkers for predicting outcomes, efficacy and toxicity.

Radiotherapy in Patients With Metastatic Esophageal Cancer Responding to PD-1 Inhibitor Plus Chemotherapy

Radiotherapy in Patients With Metastatic Esophageal Cancer Responding to PD-1 Inhibitor Plus Chemotherapy: a Patient Preference Multicenter Randomized Phase II Trial

Data obtained through this study may be provided to qualified researchers with academic interest in esophageal cancer. Data or samples shared will be coded, with no PHI included. Approval of the request and execution of all applicable agreements (i.e. a material transfer agreement) are prerequisites to the sharing of data with the requesting party.

To explore the dynamic changes of circulating tumor DNA (the frequency of specific mutations by Next-generation sequencing Methodology) from baseline, before and after radiotherapy.

Overall survival was defined as the time from first dose to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS is reported for all participants of the Intent-To-Treat (ITT) population. The Kaplan-Meier method was used to calculated the 1-year survival probability.

Median progression-free survival (PFS), was defined as the time from first dose to the first documented progressive disease (PD) per RECIST 1.1 as assessed by the investigator, or death due to any cause, whichever occurred first.

Acute toxicity Rate, was defined as the frequency of toxicities related to the treatment, which arises within one month after administration, according to National Cancer Institute Common Terminology Criteria for Adverse Event,Version 5.0 (CTC AE5.0).

Late toxicity rate, was defined as the frequency of toxicities related to the treatment, which arises after one month after administration, according to National Cancer Institute Common Terminology Criteria for Adverse Event,Version 5.0 (CTC AE5.0).

The score of the participants evaluated by The EORTC core quality of life questionnaire (QLQ-C30). All of the scales and single-item measures range in score from 0 to100.A high scale score represents a higher response level. Thus a high score for a functional scale represents a high/healthy level of functioning.

The score of the participants evaluated by The EORTC Quality of Life Questionnaire - Oesophageal Cancer Module (EORTC QLQ-OES18). All of the scales and single-item measures range in score from 0 to100.A high scale score represents a higher response level. Thus a high score for a functional scale represents a high/healthy level of functioning.

Peking University Cancer Hospital & Institute

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Nervous System Diseases

Eye Diseases

Symptoms and General Pathology

Behaviors and Mental Disorders

Prostatic Neoplasms

Vision Disorders

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Sensation Disorders

Neurologic Manifestations

Quality of Life

Androgens

Hormones

Hormone Antagonists

Participants will receive 6 months of standard-of-care androgen deprivation therapy (ADT) and radiation therapy.

Participants will receive 6 months of apalutamide and radiation therapy.

Participants will receive 24 months of standard-of-care androgen deprivation therapy (ADT) and radiation therapy.

Participants will receive 6 months of ADT, apalutamide, and radiation therapy.

Apalutamide

Androgen Deprivation Therapy

Karen Hoffman, MD

1. Personalize treatment for prostate cancer based on how aggressive the disease is and
2. Learn if apalutamide-based treatment can help to reduce fatigue and other side effects of treatment in participants who are being treated with radiation therapy for prostate cancer, as compared to standard therapy.

Primary Objective:

ARTERA LOW COHORT (less aggressive disease)

1) To compare fatigue at 9 months, as assessed by FACIT-F, between participants assigned to six months of apalutamide monotherapy versus six months of GnRH-based ADT.

HIGHER RISK COHORT (more aggressive disease)

1) To compare fatigue at 24 months, as assessed by FACIT-fatigue, between participants assigned to six months of GnRH-based ADT plus apalutamide monotherapy versus 24 months of GnRH-based ADT.

Secondary Objectives for both Cohorts:

1. To compare patient-reported quality of life for the two treatment arms (Arm 1 vs. 2 for Artera-Low Cohort and Arm 3 vs. 4 for Artera-High Cohort) as measured by FACT-P and EPIC-26.
2. To compare physician-reported toxicity for the two treatment arms as measured by CTCAE v 5.
3. To compare patient-reported activity levels for the two treatment arms as measured by the leisure-time activity questionnaire.
4. To compare patient activity and sleep for the two treatment arms as measured by participant wearable health bands.
5. To compare cognitive function for the two treatment arms as measured by PROMIS-CF and the Symbol Digit Modality test.
6. To compare mental health for the two treatment arms as measured by the Health Anxiety and Depression Scale.
7. To compare changes in HgA1c and Lipid profiles over time between the two treatment arms.
8. To compare time to testosterone recovery between treatment arms.
9. To compare time to next therapy between treatment arms.
10. To compare progression-free survival, metastasis-free survival, cancer specific mortality and overall survival between treatment arms.
11. To compare risk of major acute coronary event between treatment arms.
12. In the subset of patients who agree to optional body composition measurements, to compare change in body composition including visceral fat and skeletal muscle mass between treatment arms.

Exploratory Objectives for both Cohorts:

1. In the subset of participants who agree to correlative studies, to evaluate the association between fatigue and circulating inflammatory cytokines.
2. In the subset of participants who agree to germline testing, to determine if inherited variants in steroidogenic genes influence individual body composition toxicity with androgen signaling inhibition.
3. To evaluate how germline variants interact with tumor intrinsic properties (via Artera) to determine the overall benefit patients derive from finite, intense androgen signaling inhibition in the post-operative setting.
4. To investigate the relationship between plasma exosomes, Artera tissue pattern, and the germline to somatic interaction.
5. To study the overlap between body composition toxicity and risk for coronary artery disease as measured by radiographic coronary calcifications and lab markers of coronary artery disease.
6. To evaluate the association between radiation plan metrics and patient-reported urinary and bowel functional changes.

PROSTATE-IQ: Parallel RandOmized STudy of Personalized Apalutamide Treatment and Evaluation to Improve Quality of Life in Post-Operative Radiation With Androgen Axis Suppression. A Phase III Multi-center Study for Men With Detectable PSA After Prostatectomy for Prostate Cancer.

Score scale ranges (0-4) 0 - Not at all

1. - A little bit
2. - Somewhat
3. - Quite a bit
4. - Very Much

Janssen Scientific Affairs, LLC

M.D. Anderson Cancer Center

Recurrence

Disease Attributes

Reproductive Control Agents

Prolactin Release-Inhibiting Factors

Triptorelin Pamoate

Bicalutamide

Androgen Antagonists

Nonsteroidal Anti-Androgens

Patients with locally recurred prostate cancer will receive a ultrahypofractionated stereotactic radiotherapy to the radiologically identified lesion (Dose: 5 fractions with 7Gray every second work week day) combined with an androgen deprivation therapy (LHRH-agonist / -antagonist) for 6 months.

Ultrahypofractioned radiotherapy for patients with isolated local recurrence after radical prostatectomy in 5 fractions

Ultrahypofractionated salvage radiotherapy to a local recurrence after radical prostatectomy

In combination to the radiotherapy a short term androgen deprivation drug for 6 months will be applied.

The drug concept used is:

- LHRH(Luteinizing hormone releasing hormone)-agonist with 3-month subcutaneous depot injection (e.g. Pamorelin® LA (Triptorelin) 11.25mg s.c.) in combination with nonsteroidal antiandrogen (e.g. Bicalutamide 50mg/day) as flare protection at least 5 days before and max. 15 days after first LHRH-injection

Androgen deprivation therapy

Mohamed MS Shelan, Assistant Professor

Mohamed MS Shelan, PD

The main objective of the trial is to explore the efficacy and safety of combining short-term androgen deprivation therapy (ADT) over 6 months to focal ultrahypofractionated salvage radiotherapy (SRT) delivered in 5 fractions to the site of local recurrence within the prostate bed after radical prostatectomy where multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen (PSMA) PET/CT are used to precisely identify the local recurrence and compare it to previously published literature.

Trial of Ultrahypofractionated Focal Salvage Radiotherapy for Isolated Prostate Bed Recurrence After Radical Prostatectomy

A Single Arm Phase II Trial of Ultrahypofractionated Focal Salvage Radiotherapy for Isolated Prostate Bed Recurrence After Radical Prostatectomy

The initial prostate specific antigen (PSA) at time of registration will be the starting point. Freedom from biochemical progression is counted from the day of registration to the day of either first recorded biochemical progression as defined below, clinical progression or death due to clinical progression.

Biochemical relapsefree survival measured with PSA (prostate specific antigen) lab testing at 1, 3, 6, 12, 18 and 24 months after radiotherapy. The duration of biochemical relapsefree survival is measured and documented in months for each patient.

A biochemical recurrence is defined by any confirmed PSA rise above 0.20 ng/mL with a confirmatory rise at least 2 weeks later. For those patients whose PSA does not drop below 0.20 ng/mL at time of first response assessment at 3 months are considered as non-responders to treatment and are considered to have a biochemical recurrence in case a second measurement at least 2 weeks later confirms a rising PSA above this level.

Standard acquisition of therapy related acute side effects of grade 3 or higher according to NCI CTCAE v5.0 at radiotherapy end and at 1 and 3 months after radiotherapy will be assessed. The side effects are recorded with the corresponding grade according to the NCI CTCAE v5.0 scale at the measured points of time.

Special attention shall be given to diarrhea, fecal incontinence, proctitis, rectal hemorrhage, rectal pain, hematuria, urinary frequency, urinary urgency, urinary retention, urinary incontinence, cystitis non-infective and erectile dysfunction.

Clinical progression-free survival is defined as time between registration and the appearance of a new recurrence (any N1 or M1) as suggested by PET-CT, symptoms related to progressive prostate cancer (PC), or death due to any cause.

The duration of clinical progression-free survival is measured and documented in months for each patient.

Definition of recurrence:

* A local recurrence is defined as the appearance of evidence of a recurrence within the prostate bed. Confirmation of the recurrence by biopsy is recommended, whenever possible.
* A regional nodal recurrence is defined as a radiographic (PET-CT) evidence of a lymphadenopathy in the pelvis in a patient without the diagnosis of hematologic/lymphatic disorder
* Distant recurrence is defined as the appearance of distant metastases (M1a, M1b, M1c) outside the pelvis.

Metastasis-free survival is defined as time between registration and the appearance of a metastatic recurrence (any M1) as suggested by PET-CT or death due to any cause. The duration of metastasis-free survival is measured and documented in months for each patient.

Patients without any of the events of interest (including those with biochemical relapse only) are censored at the date of the last follow-up. Second cancers are not considered events in terms of this endpoint. In case of biochemical progression, re-staging will be made with PET-CT imaging preferably with the same tracer used before registration. In case of negative PET findings at biochemical relapse, a new PET imaging should be repeated on a 6-monthly basis or earlier in case clinically indicated.

Standard acquisition of therapy related late side effects according to NCI CTCAE v5.0 at 6, 12, 18 and 24 months after radiotherapy. The side effects are recorded with the corresponding grade according to the NCI CTCAE v5.0 scale at the measured points of time.

Special attention shall be given to diarrhea, fecal incontinence, proctitis, rectal hemorrhage, rectal pain, hematuria, urinary frequency, urinary urgency, urinary retention, urinary incontinence, cystitis non-infective and erectile dysfunction.

All patients registered into this trial are to complete QoL questionnaires at registration and at 1, 3, 6, 12, 18, 24 months after radiotherapy. A longitudinal design is used. Patients are asked to complete the EORTC Quality of life questionnaire C-30 version 3. The resulting score will be documented at each point of time.

All patients registered into this trial are to complete QoL questionnaires at registration and at 1, 3, 6, 12, 18, 24 months after radiotherapy. A longitudinal design is used. Patients are asked to complete the EORTC Quality of life questionnaire PR25 prostate cancer module. The resulting score will be documented at each point of time.

University of Bern

Debiopharm International SA

Werner und Hedy Berger-Janser - Stiftung

Insel Gruppe AG, University Hospital Bern

Anti-Inflammatory Agents

Abiraterone Acetate

Prednisone

Testosterone

Glucocorticoids

Antineoplastic Agents, Hormonal

* GnRH agonist injection monthly or every 3 months for 6 months
* Bicalutamide by mouth once/day for 6 months
* Salvage radiation (starting 4-10 weeks after initiation of ADT)

* GnRH agonist injection monthly or every 3 months for 6 months
* Abiraterone acetate by mouth once/day for 6 months
* Prednisone by mouth once/day for 6 months
* Apalutamide by mouth once/day for 6 months
* Salvage radiation (starting 4-10 weeks after initiation of ADT)

-blocks the function of hormones including testosterone which prostate cancer uses to grow and spread

GnRH

Salvage radiation

Abiraterone

Prednisone is a corticosteroid. It prevents the release of substances in the body that cause inflammation. It also suppresses the immune system.

Paul Nguyen, MD

This research study is comparing two different combinations of androgen deprivation therapy (ADT) used together with radiation as a treatment for rising PSA after radical prostatectomy (prostate cancer).

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that an intervention is being studied. In this study, the investigational agents are apalutamide and abiraterone acetate.

Currently, the best standard treatment for men with this type of prostate cancer includes radiation therapy combined with androgen deprivation therapy (ADT). ADT blocks the function of hormones including testosterone which prostate cancer uses to grow and spread. All participants in this study will receive the main standard form of ADT called a luteinizing hormone-releasing hormone agonist (LHRHA). Physicians often also use another drug called bicalutamide to help the LHRHA block hormone function. The investigators are testing whether using two newer anti-hormonal drugs called abiraterone acetate and apalutamide with LHRHA can improve cure rates compared to using bicalutamide plus LHRHA. These two drugs work together to suppress both testosterone and the receptor where testosterone binds thereby providing more potent hormone suppression.

Randomized Phase II Study of Salvage XRT + ADT +/- Abiraterone and Apalutamide for Rising PSA After RP (FORMULA-509)

Randomized Phase II Study of Salvage XRT + ADT +/- Abiraterone Acetate and Apalutamide (ARN-509) for Rising PSA After Radical Prostatectomy With Adverse Features.(FORMULA-509 Trial)

Time from randomization to PSA failure or death due to any cause

Time from randomization to distant metastasis, identified on conventional imaging (CT, bone scan, or MRI) or pathologically, or death due to any cause or censored at date last known alive.

Time from randomization to distant metastasis, visible only by PET portion of a PET-CT, or death due to any cause or censored at date last known alive.

The interval from randomization to the date of last known follow-up alive or date of death from each of the following causes: prostate cancer, cardiovascular disease, other causes.

Time from randomization to death due to any cause or censored at date last known alive

Time from randomization to date at which testosterone level returns to a normal level, or censored at the date of last disease evaluation for those whose testosterone has not reached a normal level

Measure Grade 1-5 toxicities at study visits and follow-up using the CTCAE v.4.0 forms and determine attribution

Time from randomization to date at which ADT is restarted for disease progression. Censoring occurs at date of last disease evaluation for those who are not restarted on ADT.

Patient-reported Quality of Life will be measured by a fatigue questionnaire

Patient-reported Quality of Life will be measured by a questionnaire assessing symptoms related to prostate cancer

Patient-reported Quality of Life will be measured by a memory survey

Time from randomization to date at which first cardiovascular event (myocardial infarction, stroke, deep venous thrombosis, or pulmonary embolism) occurs. Censoring occurs at date of last disease evaluation for those who did not have a cardiovascular event.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Radiotherapy in Patients With Metastatic Esophageal Cancer Responding to PD-1 Inhibitor Plus Chemotherapy	NCT06084897	Esophageal Neop... Esophageal Canc...	TP (Paclitaxel ... PD-1 inhibitor Consolidation R... Salvage Radiati...	18 Years -	Cancer Institute and Hospital, Chinese Academy of Medical Sciences
PROSTATE-IQ: Parallel RandOmized STudy of Personalized Apalutamide Treatment and Evaluation to Improve Quality of Life in Post-Operative Radiation With Androgen Axis Suppression. A Phase III Multi-center Study for Men With Detectable PSA After Prostatectomy for Prostate Cancer.	NCT06274047	Androgen Axis S... Prostatectomy Prostate Cancer	Apalutamide Androgen Depriv...	18 Years -	M.D. Anderson Cancer Center
Trial of Ultrahypofractionated Focal Salvage Radiotherapy for Isolated Prostate Bed Recurrence After Radical Prostatectomy	NCT05746806	Recurrent Prost...	Ultrahypofracti... Androgen depriv...	18 Years - 100 Years	Insel Gruppe AG, University Hospital Bern
Randomized Phase II Study of Salvage XRT + ADT +/- Abiraterone and Apalutamide for Rising PSA After RP (FORMULA-509)	NCT03141671	Prostate Cancer	GnRH Bicalutamide Salvage radiati... Abiraterone Prednisone Apalutamide	18 Years - 95 Years	Dana-Farber Cancer Institute
PROSTATE-IQ: Parallel RandOmized STudy of Personalized Apalutamide Treatment and Evaluation to Improve Quality of Life in Post-Operative Radiation With Androgen Axis Suppression. A Phase III Multi-center Study for Men With Detectable PSA After Prostatectomy for Prostate Cancer.	NCT06274047	Androgen Axis S... Prostatectomy Prostate Cancer	Apalutamide Androgen Depriv...	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for salvage radiation