Neoplasms

Symptoms and General Pathology

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Neoplasm Metastasis

Prostatic Neoplasms

Recurrence

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Disease Attributes

All Drugs and Chemicals

Antineoplastic Agents

Reproductive Control Agents

Androgens

Leuprolide

Goserelin

Triptorelin Pamoate

Bicalutamide

Antineoplastic Agents, Hormonal

Contraceptive Agents

Contraceptive Agents, Female

Contraceptive Agents, Hormonal

ARM 1:

LHRH analogues for 6 months + bicalutamide 50 for 30 days

LHRH analogues for 24 months + bicalutamide 50 for 30 days

ADT will consist of LHRH analogues (triptorelin, goserelin, leuprorelin) with bicalutamide 50 mg/day started 10 days before the first ADT injection to avoid LHRH-related flare-ups. Bicalutamide will be discontinued after 30 days. The LHRH analogue will be initiated prior to the start of radiotherapy and administered for 6 or 24 months depending on treatment allocation. The maximum time permitted between randomisation and administration of the first LHRH dose is 30 days. The maximum time from the first LHRH dose to the start of SRT is 60 days.

triptorelin, goserelin, leuprorelin

Pablo Raña, PhD

Anna Maria Boladeras, MD

Victor Duque, MD

Alfonso Gómez, MD

Xavier Maldonado, MD

Joel Mases, MD

Gemma Sancho, MD

Felipe Couñago, MD

Carmen González, MD

Fernando López, MD

Aurora Rodríguez, MD

Noelia Sanmamed, MD

Jesús Oliveira, MD

Luis Alberto Glaria, MD

Antonio José Conde, MD

The optimal indication for ADT has long been a point of controversy, at least until the results of randomised trials comparing RT with and without ADT were published. NCCN guidelines and most retrospective series and left the decision to prescribe ADT in combination with RT to the discretion of the treating physician, despite a lack of clear scientific evidence to support this recommendation. The percentage of patients in those retrospective series who received hormone therapy ranged from 33% to 71%, but generally involved patients with adverse prognostic factors (Gleason score \> 7, stage pT3-T4, PSA \> 1 ng/mL in cases with biochemical recurrence \[BCR\], and PSA doubling time \[PSA-DT\] \< 6 months). Despite the heterogeneity in those studies in terms of treatment duration, RT dose, and treatment volumes, most of the studies found that ADT significantly prolonged biochemical relapse-free survival (BRFS), especially in patients with PSA levels \> 1 ng/mL at recurrence.

The results of two randomised trials evaluating SRT with or without ADT were published in 2017, with both trials demonstrating a benefit for ADT in this clinical setting. A follow-up study confirmed the value of ADT in combination with SRT in terms of better PFS and, in the RTOG study, an improvement in overall survival (OS). Despite the lack of data from phase III trials regarding the influence of PSA-DT, the BRFS interval, and the Gleason score in terms of their effects on the clinical course of patients who develop BCR, there is strong evidence from other studies to support the use of these variables (together with age and comorbidities). Given the available evidence, we believe that these variables should be considered when determining the indications for ADT.

In line with the philosophy underlying the approach used by D'Amico to develop a risk classification system for prostate cancer patients at diagnosis, we propose three risk groups. According to Pollack et al. and Spratt et al., low-risk patients would not benefit from hormone therapy, especially long-term ADT, due to the deleterious effects of such treatment. By contrast, intermediate and high risk patients would be candidates for ADT combined with RT. However, the optimal duration of ADT in these patients (6 months vs. 2 years) remains undefined and needs to be determined prospectively in a randomised trial, similar to the approach used in the DART 05.01 trial.

SRT and ADT are widely used in routine clinical practice to treat patients who develop BCR after prostatectomy. In this context, we intend to perform a multicentre, phase III trial to define the optimal duration of ADT (6 vs. 24 months).

Short Versus Long-term Androgen Deprivation Therapy With Salvage Radiotherapy in Prostate Cancer. URONCOR 0624

Short Versus Long-term Androgen Deprivation Therapy Combined With Salvage Radiotherapy in Prostate Cancer Patients With Biochemical Recurrence After Prostatectomy: a Multicentre Phase III Randomised Controlled Trial

Distant metastasis-free survival: time from administration of the first LHRH analogue (this same starting point applies to all secondary objectives) until the patient develops M1a disease (involved retroperitoneal lymph nodes) or M1b-c disease (bone/visceral involvement) according to RECIST 1.1 criteria based on conventional computed tomography (CT) imaging and bone scans. The use of advanced molecular imaging-PSMA or choline positron-emission tomography (PET)/CT-is subject to the centre-specific protocols in place at the participating hospitals; however, metastatic progression will be determined according to RECIST 1.1 criteria based on conventional imaging tests.

BRFS: time to biochemical progression defined as an increase in PSA confirmed by a second PSA determination (0.2 ng/mL above the salvage radiotherapy nadir or a sustained elevation in PSA levels).

Pelvic PFS: time to local recurrence (prostate bed) and/or N1 disease (positive lymph nodes below the aortic bifurcation) according to RECIST 1.1 criteria by conventional CT imaging and bone scan. The use of advanced molecular imaging (PSMA or choline PET/CT) will depend on centre-specific protocols; determination of metastatic progression will be based on RECIST 1.1 criteria from conventional imaging tests.

Cytotoxic treatment-free interval: time to the start of the first cytotoxic treatment or local treatment for oligorecurrence.

Time interval to castration resistance: the time to biochemical and/or clinical progression with castration levels (testosterone \< 50 ng/dL). Progression to castration resistance is defined as three consecutive increases in PSA (one-week intervals) with at least two PSA increases \> 2 ng/mL and a 50% increase over the PSA nadir, progression of bone lesions (≥ two lesions on the bone scan), progression of soft tissue lesions (RECIST 1.1 criteria), or the development of ≥ one soft tissue or visceral metastases (including lymph nodes).

time to death due to prostate cancer or treatment-related complications

Acute toxicity: toxicity (CTCAE criteria, v. 4.0; https://evs.nci.nih.gov) appearing any time from treatment initiation up to three months after completion of RT.

-Late toxicity: from 3 months to 5 years after completing RT (CTCAE v 4.0).

Quality of life (QoL): from baseline (prior to RT) to five years after completion of RT, assessed with the EORTC QLQ-C30 and QLQ-PR25 questionnaires.

Instituto de Investigación en Oncología Radioterápica - Fundación Española de Oncología Radioterápic

Digestive System Diseases

Rare Diseases

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Fluorouracil

Capecitabine

Dose-escalation plan (phase I)

Radiotherapy:

LEVEL 1: dose given at PTV-G will be 58.8Gy/28 fractions； 2.1Gy/per fraction; LEVEL 2: dose given at PTV-G will be 64.4Gy/28 fractions； 2.3Gy/per fraction; LEVEL 3: dose given at PTV-G will be 70Gy/28 fractions； 2.5Gy/per fraction Concurrent chemotherapy: 5-Fu/capecitabine/S-1+DDP or S-1 or Capecitabine

treatment group(phase I)

Radiotherapy dose was prescribed according to phase I trial results; Concurrent chemotherapy: 5-Fu/capecitabine/S-1+DDP or S-1 or Capecitabine

treatment group (phase II)

Wei-Xiang Qi, Dr.

shengguang zhao, Dr.

Wei-Xiang Qi

Esophageal cancer (EC) ranks the seventh most diagnosed malignant tumor (572,000 new cases) and the sixth cancer-related mortality (509,000 deaths) worldwide in 2018. The incidence of EC is strikingly varying among the regions and sexes. Approximately 70% of EC cases occur in men, and there is a 2-fold to 3-fold difference in incidence and mortality rates between regions worldwide. According to the latest reported in 2017, esophageal cancer ranks the sixth most common cancer and the fourth leading cause of cancer-mortality in China. Currently, esophagectomy is considered as the standard treatment for resectable EC patients. However, the prognosis of stage IIA-III esophageal cancer after esophagectomy remains poor, and local regional lymph node recurrence is the major patterns of recurrence, and mediastinal lymph node recurrence is one of the most common sites. Previous retrospective study has found that salvage chemoradiotherapy is a effective treatment option for these patients. However, the optimal dose remains unknown. In addition, no prospective trials have been conducted to investigate the efficacy and toxicities of salvage chemo-radiotherapy by using simultaneous integrated boost for the treatment of mediastinal lymph node recurrence after radical surgery of esophageal Cancer

Simultaneous Integrated Boost for Mediastinal Lymph Node Recurrence After Radical Surgery of Esophageal Cancer

Phase I/II Dose Escalation by Simultaneous Integrated Boost for Mediastinal Lymph Node Recurrence After Radical Surgery of Esophageal Cancer

DLT was defined as grade 4 or higher hematological toxicities and/or grade 3 or higher nonhematological toxicities.

Survival time was measured from the date of study enrollment to the date of death or last follow-up;

late toxicity were grade according to RTOG and CTCAE criteria

acute toxicity were grade according to CTCAE criteria

From treatment initiation to first documented local progression or death or censor

Ruijin Hospital

associate chief physician

Hypoglycemic Agents

Anti-Allergic Agents

Antiemetics

Central Nervous System Depressants

Gastrointestinal Agents

Dermatologic Agents

Metformin

Diphenhydramine

Promethazine

* Metformin - 850mg PO BID; 48 weeks
* Salvage radiotherapy SRT - 35 x 2Gy; 7 weeks

- Salvage radiotherapy SRT - 35 x 2Gy; 7 weeks

Salvage Radiotherapy SRT

Daniel M. Aebersold, Prof

Alan Dal Pra, MD

The main objective of the trial is to explore the efficacy of salvage radiotherapy (SRT) plus metformin compared to SRT in the endpoint of time to progression after prostatectomy failure.

Although the use of salvage radiotherapy (SRT) is the only potentially curative treatment after prostatectomy failure, it has provided suboptimal results over the years. Metformin may represent an effective and inexpensive means to improve SRT outcomes with a favorable therapeutic ratio. Taken pre-clinical and retrospective clinical data together, there is a compelling rationale for conducting a RCT with SRT and metformin. Herein we propose a multicenter, randomized, open-label, proof-of-concept phase II trial with the hypothesis that the addition of metformin to SRT can delay time to progression compared to the standard-of-care SRT. The study has 1:1 randomization and stratification variables include Gleason score, PSA at SRT, surgical margin status and ADT use.

SAKK 08/15 - PROMET - Salvage Radiotherapy +/- Metformin for Patients With Prostate Cancer After Prostatectomy

SAKK 08/15 - PROMET - Multicenter, Randomized Phase II Trial of Salvage Radiotherapy +/- Metformin for Patients With Prostate Cancer After Prostatectomy

The primary endpoint of the trial is time to progression (TTP), defined as time from randomization until one of the following events, whichever comes first:

* Biochemical progression
* Clinical progression
* Death due to clinical progression

PFS is defined as time from randomization until one of the following events, whichever comes first:

* Biochemical progression
* Clinical progression
* Death from any cause

Undetectable PSA is defined as a serum PSA value of ≤0.05 ng/mL for at least two consecutive measurements after the last radiotherapy fraction and up to 18 months thereafter. To count as undetectable PSA under normal testosterone levels, the testosterone level has to be ≥50 ng/dL (i.e. a non-castrate testosterone level).

50% PSA response is defined as a ≥50% PSA decline after radiotherapy compared to the serum PSA level at randomization up to 18 months after last radiotherapy fraction.

Clinical progression-free survival will be calculated as the time from randomization until clinical progression or death due to any cause.

Time to further anti-cancer systemic therapy (e.g. hormonal treatment) is defined as the time from randomization to the start of any type of salvage systemic treatment.

Prostate cancer-specific survival will be calculated as the time from randomization to the date of death due to prostate cancer.

Overall survival will be calculated as the time from randomization to the date of death from any cause.

AEs will be assessed according to NCI CTCAE v4.03.

Swiss Group for Clinical Cancer Research

Patients with early biochemical relapse of prostate cancer following radical prostatectomy who have a PSA greater than or equal to 0.1 to less than 0.3 ng/mL with negative PSMA PET/CT will go on surveillance. Routine PSA will be conducted and a repeat PSMA PET/CT imaging will be conducted when the PSA rises to greater than 0.5 to less than 1.0 ng/mL.

Patients with early biochemical relapse of prostate cancer following radical prostatectomy who have a PSA of greater than or equal to 0.1 to less than 0.3 ng/mL with negative PSMA PET/CT will receive salvage radiotherapy to the prostate bed. This radiotherapy may or may not include the pelvic lymph nodes.

Standard of care salvage radiotherapy to the prostate bed which may include the lymph nodes.

Salvage radiotherapy

Srinivas Raman, MD

The investigators will randomize patients presenting with early BCR with a negative baseline PSMA PET/CT, to upfront SRT or surveillance. Early BCR is defined as a PSA relapse of \>0.1 to \<0.3 ng/mL. Patients in the surveillance arm will be monitored with PSA every 3 months. A repeat PSMA PET/CT will be undertaken when the PSA reaches a target level of \>0.5 to \<1.0 ng/mL. Both early radiation treatment and surveillance with repeat PSMA PET/CT imaging are within patterns of practice locally; therefore, the investigators believe that there is clinical equipoise on this subject.

Timing of Post-prostatectomy PSMA Imaging

A Phase II Randomized Feasibility Study Comparing Early Salvage Radiotherapy Versus Surveillance With Delayed Repeat PSMA PET/CT Imaging in Patients Presenting With Early Biochemical Relapse of Prostate Cancer Following Radical Prostatectomy

This study will assess the feasibility of surveillance with delayed repeat PSMA PET/CT in patients with BCR of prostate cancer following radical prostatectomy with negative baseline PSMA PET/CT. A treating physician questionnaire will be completed prior to screening and enrollment, as well as PSA results every three months for surveillance patients.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Short Versus Long-term Androgen Deprivation Therapy With Salvage Radiotherapy in Prostate Cancer. URONCOR 0624	NCT05781217	Prostate Cancer Salvage Radioth... Biochemical Rec... Androgen Depriv... Metastases-free...	triptorelin, go...	18 Years -	Instituto de Investigación en Oncología Radioterápica - Fundación Española de Oncología Radioterápic
Simultaneous Integrated Boost for Mediastinal Lymph Node Recurrence After Radical Surgery of Esophageal Cancer	NCT03990532	Esophageal Canc... Salvage Radioth... Dose-escalation Mediastinal Lym...	treatment group... treatment group...	18 Years - 80 Years	Ruijin Hospital
SAKK 08/15 - PROMET - Salvage Radiotherapy +/- Metformin for Patients With Prostate Cancer After Prostatectomy	NCT02945813	Prostate Cancer	Metformin Salvage Radioth...	18 Years - 75 Years	Swiss Group for Clinical Cancer Research
Timing of Post-prostatectomy PSMA Imaging	NCT05008900	Prostate Cancer Prostatectomy	Salvage radioth...	18 Years -	University Health Network, Toronto

Spots Global Cancer Trial Database for salvage radiotherapy