Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

EXTERNAL RADIOTHERAPY

The generation of predictive models in radiotherapy has seen a significant increase. In 2017, Raymond published the largest systematic review of predictive prognostic models for biochemical relapse (BR), metastasis-free survival, and overall survival in patients with localized prostate cancer treated with radiotherapy (14), attempting to identify whether they were adequately developed and validated.

He found 72 unique predictive models for external radiotherapy: 22 corresponding to BR risk, 20 corresponding to Cancer-Specific Survival, 10 corresponding to Overall Survival, and 20 for Disease/Metastasis-Free Survival detection. In his analysis, he highlighted a significant variation in the quality of these predictive models, understanding that they were developed prior to the existence of TRIPOD guidelines.

In this regard, he pointed out that 54% of these models did not report their accuracy, and 61% of the models lacked validation (either internal or external). He also noted that they had limited follow-up (only 65% had follow-up beyond 5 years), that the treatment doses in these models were lower than current standards, and that the radiation techniques were different from current practices. Although in his final assessment, Raymond maintains that predictive models provide more certainty in predicting oncological outcomes than professional assessments, he considers it vital to validate these models for each population that wants to use them (the vast majority of these models are based on U.S. populations) or, even better, to generate predictive models specific to the local population while adhering to the TRIPOD guidelines.

Probably due to the lack of validation in our patients for existing predictive models and/or the absence of predictive models originating from our population, in our routine clinical practice (Multidisciplinary Oncology Committees), phisycians do not apply any predictive models to patients diagnosed with localized prostate cancer.

The general objective of the study is to develop a predictive model for oncological outcomes and bladder and rectal toxicities based on the analysis of patients with localized prostate cancer who have received external radiotherapy, useful for medical decision-making. This objective is divided into three specific objectives:

1) Estimate a predictive model for oncological outcomes, such as the probability of Biochemical Recurrence (BR), Disease-Free or Metastasis-Free Time (DFT), Overall Survival (OS), and Cancer-Specific Survival (CSS).

2) Estimate a predictive model for bladder and rectal toxicities in patients with localized prostate cancer who have received external radiotherapy.

3) Analyze the feasibility and impact of implementing an individualized decision-making model based on this model, and its implementation in oncology committees and in initial (informative) visits in radiation oncology.

* Hypotheses\*\*:

  1. The developed predictive model will have adequate predictive values.
  2. Validate and compare the model with other shared decision-making methods in localized prostate cancer in Radiation Oncology Services.
  3. Professionals and patients will show appropriate satisfaction with the use of this type of model for shared decision-making with the patient in radiation oncology.
* Method\*\*:

This study is divided into phases for its execution:

1. Retrospective analysis of 400 patients diagnosed with localized prostate cancer and treated with external radiotherapy between January 2014 and December 2019. Sub-analyses of the population will be conducted to evaluate different oncological outcomes and the produced toxicities, with particular emphasis on distinguishing differences that technological variables may justify.
2. Generation and validation of a predictive model for treatment oncological outcomes and bladder and rectal toxicities. The development of the model will follow the TRIPOD guidelines.
3. Analysis of the model's implementation in patient decision-making, for which a validated questionnaire will be applied to measure satisfaction with the decision made in patients diagnosed with prostate neoplasia (15). The predictive model will be applied through a pilot study involving 30 patients who will be presented with treatment options based on different outcome scenarios. The questionnaire will be administered after the first visit to radiation oncology to assess the use of predictive models as part of the information provided. This questionnaire will evaluate improvements in the patient's knowledge of prostate cancer, clarity of personal values, decision efficacy, and reduction of uncertainty regarding the decision made.

   * Statistical Analysis\*\*:

Phase 1: The annual incidence rate will be calculated using the actuarial method for oncological outcomes, estimating the annual number of cases divided by the sum of the total person-years at risk per 100 treated patients. Rates will be calculated as crude and age-standardized rates, stratified by relevant sociodemographic and clinical characteristics. Rates will be summarized as cumulative incidences over time using a Kaplan-Meier estimator. Individual associations between predictive factors and complication outcomes will be calculated using a bivariate binomial logistic prediction model. The optimal prediction time will be estimated by comparing changes in odds at different time-to-event cutoff points.

Phase 2: The risk prediction model will be constructed using penalized logistic regression techniques to optimize predictive accuracy for the occurrence of oncological outcomes. Model development will be conducted on a subset of training data using k-fold validation, and diagnostic prediction will be calculated using the recalibrated algorithm. The predictive model's performance will be evaluated by calculating the area under the receiver operating characteristic curve and other measures of accuracy for various cutoff points (percentage of patients at maximum risk, maximization of positive and negative predictive value, and F-score).

Phase 3: The predictive model will be applied to 30 new patients. Mean satisfaction with the provided information will be estimated using questionnaire results. Changes in uncertainty before and after receiving information will be assessed using paired-sample t-tests.

Generation and Validation of Predictive Models for Localized Prostate Cancer Treated With External Radiotherapy.

Generation and Validation of Predictive Models for Localized Prostate Cancer Treated With External Radiotherapy

As the time in months from diagnosis until death or the last follow-up.

Grade II toxicity in bladder and rectal , according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.03).

Consorci Sanitari de Terrassa

Uterine Cervical Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

A Library of treatment plans will be generated for each patient before starting radiochemotherapy (standard treatment). This Library will be created using CT-Scans with variable bladder filling (and hence different uterine positions). Each day of radiotherapy treatment, an appropriate plan is chosen based on Imaging that day.

Each patient will have 3 scanners before treatment initiation. One corresponding to an empty bladder, one to an "intermediate" one, one to a full bladder.

Adaptative treatment plan

At the time of each fraction of external radiotherapy, the most appropriate plan (empty, intermediate, full bladder) covering the target and sparing the organs at risk is chosen.

External radiotherapy

This study evaluates the effect of adaptative Intensity-Modulated Radiation Therapy (IMRT) in the treatment of locally advanced cervical cancer on acute genito-urinary (GU), and gastrointestinal (GI) toxicities. Every patients will be treated according to the adaptative IMRT strategy.

Adaptative Radiotherapy for Locally Advanced Cervical Cancer

Phase II Study of Adaptative Radiotherapy for Locally Advanced Cervical Cancer

Center Eugene Marquis

Symptoms and General Pathology

Neoplasm Metastasis

Pain

Neoplastic Processes

The radiation technique used for each patient will be based on local clinical practices and on number of vertebae to treat between 1\*8 Gy; 5\*4 Gy and 10\*3 Gy

Percutaneous vertebroplasty

Bertrand BR RICHIOUD, MD

The purpose of this study is to evaluate cost-utility analysis in order to provide recommendations to French decision-makers between vertebroplasty and radiation therapy in Bone spine metastases. Indeed, radiation therapy is often advocated a systematic way. The object of this study would be to expand the use of vertebroplasty.

Moreover, this study assess to the strategy impact on the pain control reduction and functional preservation. In fact, analgesic effect is achieved differently depending on the procedure used.Eligible patients will be recruited and registered consecutively. Patients will be randomly,

This is a health-economic multicenter, prospective, randomized with stratification according to number of vertebrae to treat (1-3 vertebrae vs 4-6 vertebrae) and center :

* Arm A: Percutaneous vertebroplasty
* Arm B: External radiotherapy

This is an open-label study. The expected total study period is 2.5 years (enrolment: 2 years, patient follow-up: 6 months). A total number of 304 patients with spine metastases will be recruited (152 patients/arm).

Bone is the most common site for metastasis. In breast and prostate cancers, 70% of patients dying of their cancer have evidence of metastatic bone disease \[Coleman, 2006\]. Depending on their localization, bone metastases can have debilitating consequences resulting in considerable morbidity and complex demands on health care resources. Bone spine metastases are the most frequent site observed in patients with cancer of the lung, prostate, breast and hemopoetic organs. The occurrence of spinal metastases in patients with advanced cancer can cause significant morbidity, with pain and/or neurological deficit adversely affecting the patients' quality of life.

Interventional radiology takes a large place in the treatment of bone metastases. Currently, vertebroplasty appears as the most satisfactory technique for stabilization of spine metastases offering a significant improvement of the quality of life. The analgesic effect is achieved very rapidly, i.e. usually within 24 hours post-procedure. Based on several publications, around 90% of patients reported rapid pain relief following vertebroplasty with 60 to 70% of complete pain relief \[Mendel, 2009\].

Radiotherapy also plays a very important role in the palliative treatment of the metastatic bone. Radiotherapy is effective and well tolerated. A reduction of the pain is noticed for 70 to 80 % of the patients and begins one or two weeks after the treatment. In all, the radiotherapy increases the quality of life of the patients and can reduce the intake of analgesics \[Lutz, 2011\].

In a lot of cases, vertebroplasty or radiotherapy can both be performed for a same painful patient (the National Institute for Health and Clinical Excellence (NICE) approved the use of vertebroplasty for patients with spinal metastases in November 2008). Radiotherapy remains the gold-standard treatment. However, vertebroplasty could be less costly and more effective compare to radiotherapy. In fact, the superiority of vertebroplasty has been demonstrated at least in the acute post-therapeutic period with (i) more rapid autonomy recovery, (ii) reduction of antalgic intakes, and potentially less side-effects.

Health Economics Evaluation of Percutaneous Vertebroplasty Compared to Radiation Therapy in Patients With Painful Spine Metastases.

To perform a cost-utility analysis in order to provide recommendations to French decision-makers on the treatment of patients with painful spine metastases.

Incremental cost-effectiveness ratio expressed in cost per quality adjusted life year (QALY) gained

Cost-assessment, Quality of life (EQ-5D) Quality adjusted life year,

Centre Leon Berard

Respiratory Tract (Lung and Bronchial) Diseases

Ear, Nose, and Throat Diseases

Laryngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Laryngeal Diseases

Respiratory Tract Diseases

Respiratory Tract Neoplasms

Otorhinolaryngologic Diseases

IORT

surgery

Xinyuan Gong

The incidence of laryngeal cancer accounts for about 1 \~ 5% of the total body tumors. For the surgical treatment of laryngeal cancer, the development trend of laryngocarcinoma treatment is to improve the local control rate, preserve the laryngeal function of patients as far as possible, and improve the life quality of patients. The efficacy, safety and feasibility of intraoperative radiotherapy (IORT) in head and neck cancer has been demonstrated in multiple institutional (3-5) studies to optimize local control. It is still unclear whether IORT can improve the local control and have efficacy, safety and feasibility in clinic. The purpose of this study was to observe the efficacy, safety and feasibility of IORT in local advanced laryngocarcinoma .

IORT in Local Advanced Laryngocarcinoma

Study of Safety and Feasibility With or Without Intraoperative Radiation in Local Advanced Laryngocarcinoma

Pharyngeal fistula means that saliva is stored in subcutaneous or subincisional tissues, resulting in abscess cavity rupture to the skin or incision margin, making the hypopharyngeal and esophageal lumen communicate with the skin to form a sinus tract, through which saliva or food can spill out to the skin, forming a skin fistula.

In this study, no matter whether distant metastases occurred, if there was the presence of any anastomotic or lateral node recurrences, it was defined as local recurrence.

Criteria for local recurrence include (1) MRI results suggests local tumor recurrence, (2)Laryngoscopy indicates local tumor recurrence.

Compare 2-year disease free survival in patients with local advanced laryngocarcinoma treated with or without IORT.

Criteria for disease free survival means MRI and laryngoscopy (PET-CT if possible) indicate tumor free.

Compare 2-year overall survival in patients with local advanced laryngocarcinoma treated with or without IORT.

Compare the risk of tissue necrosis as determined visually by the Laryngoscope at 2 years after treatment in patients with local advanced laryngocarcinoma treated with or without IORT.

Compare the risk of fibrosis as determined visually by the Laryngoscope at 2 years after treatment in patients with local advanced laryngocarcinoma treated with or without IORT.

Compare the time of wound healing after surgery in patients with local advanced laryngocarcinoma treated with or without IORT.

Tianjin First Central Hospital

director of head and neck surgery division

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Analgesics

All Drugs and Chemicals

Bone Density Conservation Agents

Zoledronic Acid

All patients receive a total dose of 27 Gy divided into 3 fractions of 9 Gy performed at least 48 hours apart each, for a treatment to J1, J3 and J5

external radiotherapy

The administration of zoledronic acid as defined under the Authorisation on the Market.

Acide zoledronic

This study will determine the delayed neurotoxicity (12 months) of a hypofractionated high dose irradiation (3 Gy x 9) associated with zoledronic acid.

The administration of zoledronic acid repeat dosages defined under the Authorisation on the Market.

All patients receive a total dose of 27 Gy divided into 3 fractions of 9 Gy performed at least 48 hours apart each, for a treatment to J1, J3 and J5.

ZOLEDRONIC ASSOCIATED With Hight Hypofractionated Radiotherapy Dose in Bone Metastases Vertebral Prostate Adenocarcinoma

STUDY OF PHASE ID'ACIDE ZOLEDRONIC ASSOCIATED WITH A STRONG DOSE Hypofractionated Radiotherapy in Bone Metastases Vertebral Prostate Adenocarcinoma

Institut Cancerologie de l'Ouest

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Thoracic Neoplasms

Lung Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

Nimotuzumab

Antineoplastic Agents, Immunological

Radiotherapy for first 2 weeks, 10 daily fractions of 30Gy 2 additional fractions to be added if desirable

nimotuzumab

Gwyn Bebb, MD

Anthony Brade, MD

This is a Phase I-II study designed to investigate nimotuzumab (TheraCIM h-R3) in combination with external radiation in patients with non-small cell lung cancer. The purpose of the Phase I portion of the study is to evaluate the safety and feasibility of the administration of nimotuzumab with palliative radiation in patients who are unsuitable for radical therapy and to select the optimal dose for the Phase II component of the study. The primary objective for the Phase II portion of the study is to examine the efficacy of this combination treatment.

The Phase I component of this study has been completed. The Phase II is now closed to recruitment.

This is a randomized, double blind, multicenter Phase II study with Phase I lead-in. Patients enrolled in this study will receive external radiotherapy with or without nimotuzumab (TheraCIM h-R3). The objective of the Phase I component of the study is to evaluate the safety and feasibility of the administration of nimotuzumab with palliative radiation in patients who are unsuitable for radical therapy (curative intent chemoradiation) and to select the optimal biologically effective dose (BED) for Phase II component of the study. In the Phase II component, overall survival, local and systemic response rates and quality of life will be evaluated inpatients treated with nimotuzumab in combination with palliative radiation vs. radiation alone.

The Phase I component of this study has been completed. The Phase II is now closed to recruitment.

A Study of Nimotuzumab in Combination With External Radiotherapy in Non-Small Cell Lung Cancer

A Phase I-II Clinical Study of Nimotuzumab (TheraCIM h-R3) in Combination With External Radiotherapy in Stage IIB, III and IV NSCLC

CIMYM BioSciences

YM BioSciences

Wendy Chapman, Vice President, Clinical Operations

Rare Diseases

Recurrence

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroepithelioma

Micronutrients

Anti-Infective Agents

Amino Acids

Iodine

Cadexomer iodine

Phenylalanine

Study participants with GBM receive a single administration of 4-L-\[131I\]iodo-phenylalanine (131I-IPA), followed by 18 cycles of external radiotherapy, each cycle being of 2 Gy.

Study participants will be administered in 2GBq in 3 fractions corresponding to ⅓ full dose activity (0.67 GBq for the 2.0 GBq dose level). The 1st fraction of 131I-IPA will be administered as above, 1- 3 days prior to 1st XRT. The 2nd and 3rd 131I-IPA fractions will be administered after 5-9 XRT fractions (subject to investigator's discretion and day of IMP administration) following the previous 131I-IPA fraction. The remainder of XRT fractions will be given following the 3rd 131I-IPA fraction.

Study participants will be administered in 2GBq in 3 fractions corresponding to ⅓ full dose activity (0.67 GBq for the 2.0 GBq dose level). The 1st fraction of 131I-IPA will be administered as above 1- 3 days prior to 1st XRT. The 2nd 131I-IPA fraction will be administered after all 18 XRT fractions have been completed, and the 3rd 131I-IPA fraction will be administered 1 week after the 2nd 131I-IPA fraction.

Dose escalation will be made in steps of 2.0 GBq, i.e. 4.0 (3\*1.33 GBq), 6.0 GBq (3\*2.0 GBq), up to 8.0 GBq (3\*2.67 GBq) until the maximum tolerated dose (MTD) is reached, using cohorts of N=3 patients.

Study participants will receive by intravenous infusion an escalating activity of 4-L-\[131I\]iodo-phenylalanine (131I-IPA).

Additional therapy is received in the form of externally administered radiotherapy

4-L-[131I]iodo-phenylalanine (131I-IPA)

Josef Pichler, MD

Tatjana Traub-Weidinger

A multi-centre, open-label, single-arm, dose-finding phase I/II study to evaluate safety, tolerability, dosing schedule, and preliminary efficacy of carrier-added 4-L-\[131I\]iodo-phenylalanine (131I-IPA), administered as single or repetitive injections in patients with recurrent glioblastoma multiforme (GBM), concomitantly to 2nd line external radiation therapy (XRT) - IPAX-1

The IPAX-1 study is an open-label, single-arm, randomised, parallel-group, multi-centre dose-finding study to evaluate ascending radioactive dose levels of 131I-IPA, intravenously administered using different dose schedules (fractionations), concomitantly to 2nd line XRT (36 Gy, administered in 18 fractions of 2 Gy). Gross tumour volume will be determined using contrast-enhanced MRI and amino acid-based PET imaging (18F-FET or 11C-methionine).

Patients will be included if they meet all of the following criteria:

1. Previously confirmed histological diagnosis of GBM, with current clinical or imaging evidence for first recurrence according to modified RANO criteria (2017). History of GBM standard therapy (debulking surgery, followed by radio-chemotherapy (50-60 Gy in 2 Gy fractions, temozolomide)
2. Interval since end of 1st line XRT ≥6 months
3. Amino acid-based molecular imaging (preferably 18F-FET- PETor 11C-methionine, as institutionally established) indicating pathologically increased amino acid uptake inside or in the vicinity of the tumour, clearly discernible from background activity.
4. Current indication for repeat radiation therapy as discussed at the multidisciplinary neuro-oncological tumour board meeting, planned as standard fractionated dose schedule (18\*2 Gy)
5. Gross tumour volume (GTV) of up to 4.8 cm diameter, clinical target volume (CTV) 0.5 cm margin and planning target volume (PTV) less than or equal to 0.5 cm margin
6. Male or female ≥18 years of age.
7. Karnofsky performance status (KPS) ≥70. Life expectancy of at least 16 weeks.
8. Haematological, liver and renal function test results as follows:

   * WBC: \>3\*109/L
   * Haemoglobin \>80 g/L
   * PLT \>100\*109/L
   * ALT, ALP, AST: ≤5 times upper international limit of normal (UILN)
   * Bilirubin ≤3 times UILN
   * Serum creatinine: within normal limits or \<120 μmol/L for patients aged 60 years or older
   * Urine protein dipstick: no protein
9. Female patients surgically sterile or postmenopausal for at least 2 years. Participants of generative potential agreeing to use effective contraception during the period of therapy and 6 months after the end of study.
10. Written informed consent

A patient will be excluded from participation in the trial if one or more of the following criteria are met:

1. Primary XRT dose greater than 60 Gy
2. Doses to organs at risk defined by Yasar and Tugrul (2005) exceeded or reached by prior radiation therapy; e.g. cumulative total dose on the optical chiasm greater than 54 Gy for 2 Gy/fraction
3. Multifocal distant recurrence, defined as tumour lesion outside the primary XRT field, as evidenced by amino acid-based PET imaging
4. Prior treatment with brachytherapy
5. Prior treatment with bevacizumab
6. History or evidence of delayed-type hypersensitivity (DTH)-dependent chronic infection (e.g. tuberculosis, systemic fungal or parasitic infection), potentially exacerbating under systemic corticoid therapy
7. Localisation of tumour related to brain stem or axis, unless sufficient reserve capacity (e.g. remnant resection cavity, marked atrophy) to accommodate possible post- procedural tissue reactions, or pre-therapeutic consent for emergency trepanation
8. Haemostaseologic conditions, precluding catheterisation or invasive procedures
9. Clinically significant illness or clinically relevant trauma within 2 weeks before the administration of the investigational product
10. Known impairment of liver or kidney function or known liver or kidney disease, such as hepatitis, cirrhosis, renal failure
11. Known human immunodeficiency virus (HIV) positive serology or chronically active hepatitis B or C
12. Ongoing toxicity \> grade 2 NCI-CTC (version 4.03) from previous standard or investigational therapies
13. Administration of another investigational medicinal product within 90 days prior to screening
14. Expected non-compliance with longer-term admission at isolated nuclear medicine ward
15. In pre-menopausal women: Pregnant as evidenced by a positive pregnancy test, or breast-feeding
16. Patients with known phenylketonuria

Study Design:

At the first dose level of 2 GBq, 131I-IPA will be administered in one of three different dosing regimens:

* Single dose regimen (1f group): Full 131I-IPA activity (2.0 GBq at the 2 GBq dose level) will be administered 1- 3 days prior to 1st XRT as a single injection.
* Fractionated dose regimen (3f - parallel group): 131I-IPA activity will be administered in 3 fractions corresponding to ⅓ full dose activity (0.67 GBq for the 2.0 GBq dose level). The 1st fraction of 131I-IPA will be administered as above, 1- 3 days prior to

  1st XRT. The 2nd and 3rd 131I-IPA fractions will be administered after 5-9 XRT fractions (subject to investigator's discretion and day of IMP administration) following the previous 131I-IPA fraction. The remainder of XRT fractions will be given following the 3rd 131I-IPA fraction.
* Fractionated dose regimen (3f - sequential group): 131I-IPA activity will be administered in 3 fractions corresponding to ⅓ full dose activity (0.67 GBq for the 2.0 GBq dose level). The 1st fraction of 131I-IPA will be administered as above 1- 3 days prior to 1st XRT. The 2nd 131I-IPA fraction will be administered after all 18 XRT fractions have been completed, and the 3rd 131I-IPA fraction will be administered 1 week after the 2nd 131I-IPA fraction. The 2nd and 3rd 131I-IPA injections should be given on the same day of the week, and some hours after administration of the respective XRT dose of that day. The day of IMP administration is subject to change at investigator's discretion. The three different treatment groups at the first (2.0 GBq) dose level (131I-IPA single dose 1f and 131I-IPA fractionated dose either 3f parallel or 3f sequential) will be recruited in parallel, as appropriate. Patients will be allocated to one of the three IPA dosing regimens. N=3 patients will be enrolled for each of the three treatment schedules. A 10th patient can be added to any of the three groups, in order to corroborate evidence for possible differences in safety and efficacy.

Patients at the entry dose level of 2 GBq will undergo 131I-IPA brain SPECT for tumour dosimetry (performed in all patients), whole body planar imaging for determination of biodistribution and whole body safety dosimetry. In addition, these patients will be comparatively assessed for possible differences in safety and/or efficacy among the different dosing regimens.

Dose escalation beyond 2 GBq will be made using the fractionated dosing regimen only, unless the outcome of the 2 GBq dose level suggests otherwise. The best treatment schedule (3f parallel or 3f sequential, see above) for higher doses shall be selected after completion of the 2 GBq dose level.

Dose escalation will be made in steps of 2.0 GBq, i.e. 4.0 (3\*1.33 GBq), 6.0 GBq (3\*2.0 GBq), up to 8.0 GBq (3\*2.67 GBq) until the maximum tolerated dose (MTD) is reached, using cohorts of N=3 patients.

If MTD has not been reached at 8.0 GBq, dose escalation may further proceed, increasing the dose fractions to a total dose 131I- IPA greater than 8 GBq using cohorts of N=3 as follows: 10 GBq, 3f (i.e. 3\*3.33 GBq); 12 GBq, 3f (i.e. 3\*4 GBq), etc., until MTD is reached or until a satisfactory anti-neoplastic efficacy is observed.

For assessment of possible anti-neoplastic effects during dose escalation, only amino acid-based molecular imaging (preferably 18F-FET-PET) will be used, which allows assessment of treatment-induced changes based on a single post-therapeutic imaging study.

MTD is defined as the dose level, inducing dose limiting toxicity (DLT), in not more than 1/6 of the subjects receiving such dose. MTD will be determined on day 45 from the first IPA injection. DLT is defined as grade 4 neurotoxicity or any other grade 4 toxicity according to NCI-CTC (version 4.03). If DLT is observed in 1 subject of a cohort, 3 additional patients will be treated at the same dose level, under which such toxicity occurred. If one or more of these patients (i.e. 2/4, 2/5 or 2/6) experience grade 4 toxicity, MTD will have been exceeded for the respective dose level. In such a case, 3 additional patients will be treated at the preceding dose level. Therapy-induced early necrosis, (also termed pseudo-progression, which has been associated with improved survival will not be classified as DLT if asymptomatic, or if symptomatic and at least partially reversible within three months with or without therapy. Disease progression/PsPD will be diagnosed according to the current RANO criteria (2017).

The highest dose under which no more than 1/6 of the patients experience DLT will be declared the MTD level. Safety, tolerability and evidence of anti-tumour effects will be compared between all dose levels, in order to identify a most suitable dose level (MSDL) for the phase II part. The MSDL will not necessarily be identical to the MTD, but might be selected by jointly considering efficacy, safety and radiation protection aspects. The identification of the MSDL will be made by a Drug Data Safety Monitoring Board (DSMB), based on an integrated review of efficacy and safety from the first part. Based on a comprehensive analysis of the first part results, the DSMB will make a conclusion regarding safety and efficacy, and recommend to the sponsor a dosing strategy and dose level (MSDL) for the phase II part, if merited. Prior to initiating phase II, the sponsor commits to submit a substantial amendment, containing a summary of the phase I results to the Austrian BASG, other competent authorities, and the responsible Ethics Committee, as appropriate.

Upon establishment of the MSDL, 12-22 further patients will be treated at the MSDL (Phase II). If unequivocal evidence of efficacy is observed, another 10 patients shall be included in the phase II part. It is planned to include approximately 34 (22+12) patients with recurrent GBM with the option to extend phase II study by another 10 patients if the results are encouraging (22+22 patients).

131I-IPA and Concurrent XRT in Recurrent GBM

A Multi-centre, Open-label, Single-arm, Dose-finding Phase I/II Study to Evaluate Safety, Tolerability, Dosing Schedule, and Preliminary Efficacy of Carrier-added 4-L-[131I]Iodo-phenylalanine (131I-IPA), Administered as Single or Repetitive Injections in Patients With Recurrent Glioblastoma Multiforme (GBM), Concomitantly to 2nd Line External Radiation Therapy (XRT) - IPAX- 1

Treatment-related adverse events according to NCI-CTCAE v 4.03 criteria will be captured and evaluated for each patient

Frequency of occurrence and severity of abnormal findings as measured by beats per minute

Frequency of occurrence and severity of abnormal findings as measured by mmHg

This outcome will be measured on all patients with treatment-related adverse events based on criteria as determined by the NCI CTCAE v 5.0 criteria. Results will be assessed by number of participants with abnormal laboratory values.

MTD will be calculated in cohorts of 3 patients that are evaluated for treatment-related adverse events according to NCI-CTCAE v 4.03. Dose will be escalated until such time that treatment-related grade 3 adverse events occur.

This outcome will be evaluated by comparing morphological outcomes to treatment, as assessed by imaging, between two treatment groups. The first treatment group having the dose administered in a single administration, whilst the second group will have the dose administered in three administrations

To evaluate the radiation absorbed dose to tumour from 131I-IPA

To confirm biodistribution and absorbed doses to whole body and organs from 131I-IPA

This outcome will be determined in all patients by the use of sequential CT imaging in order to determine response of the lesion to the therapy according to RANO criteria.

This outcome will be determined in all patients by the use of sequential CT imaging in order to determine the presence of pseudo progression as defined by the RANO criteria response to 131I-IPA + XRT combination therapy

This outcome will be determined in all patients through the use of the Trail Making Test

This outcome will be determined in all patients through the use of the HVLT-R

This outcome will be determined in all patients through the use of the MAE COWA test

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Generation and Validation of Predictive Models for Localized Prostate Cancer Treated With External Radiotherapy.	NCT06092918	Predictive Canc... Localized Prost...	EXTERNAL RADIOT...	18 Years - 95 Years	Consorci Sanitari de Terrassa
Adaptative Radiotherapy for Locally Advanced Cervical Cancer	NCT02937948	Uterine Cervica...	Adaptative trea... External radiot...	18 Years -	Center Eugene Marquis
Health Economics Evaluation of Percutaneous Vertebroplasty Compared to Radiation Therapy in Patients With Painful Spine Metastases.	NCT02174107	Spine Metastase...	External radiot... Percutaneous ve...	18 Years -	Centre Leon Berard
Adaptative Radiotherapy for Locally Advanced Cervical Cancer	NCT02937948	Uterine Cervica...	Adaptative trea... External radiot...	18 Years -	Center Eugene Marquis
IORT in Local Advanced Laryngocarcinoma	NCT04278638	Laryngeal Neopl...	IORT surgery External radiot...	18 Years -	Tianjin First Central Hospital
IORT in Local Advanced Laryngocarcinoma	NCT04278638	Laryngeal Neopl...	IORT surgery External radiot...	18 Years -	Tianjin First Central Hospital
IORT in Local Advanced Laryngocarcinoma	NCT04278638	Laryngeal Neopl...	IORT surgery External radiot...	18 Years -	Tianjin First Central Hospital
ZOLEDRONIC ASSOCIATED With Hight Hypofractionated Radiotherapy Dose in Bone Metastases Vertebral Prostate Adenocarcinoma	NCT01219790	Prostate Adenoc...	external radiot... Acide zoledroni...	18 Years -	Institut Cancerologie de l'Ouest
A Study of Nimotuzumab in Combination With External Radiotherapy in Non-Small Cell Lung Cancer	NCT00369447	Non-small-cell ...	External radiot... nimotuzumab	18 Years -	YM BioSciences
131I-IPA and Concurrent XRT in Recurrent GBM	NCT03849105	Glioblastoma Mu...	4-L-[131I]iodo-...	18 Years -	Telix Pharmaceuticals (Innovations) Pty Limited
Generation and Validation of Predictive Models for Localized Prostate Cancer Treated With External Radiotherapy.	NCT06092918	Predictive Canc... Localized Prost...	EXTERNAL RADIOT...	18 Years - 95 Years	Consorci Sanitari de Terrassa

Spots Global Cancer Trial Database for external radiotherapy