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Predictors of Normal Tissue Response From the Microenvironment in Radiotherapy for Prostate and Head-and-neck Cancer (MICROLEARNER)

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ClinicalTrials.gov Identifier: NCT03294122
Recruitment Status : Recruiting
First Posted : September 26, 2017
Last Update Posted : October 3, 2017
Sponsor:
Information provided by (Responsible Party):
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Brief Summary:

The main idea behind MICRO-LEARNER is to provide new insights about the response of healthy tissues to radiation by using information from the micro-environment obtained by biological measurements and imaging. This new knowledge will be included in current available predictive models of radio-induced toxicity, thus allowing to add unique biological characteristics of patients to dosimetry and treatment/clinical related variables.

MICRO-LEARNER focuses on prostate cancer (PCa) and head-and-neck cancer (HNCa). For both cancers, radiotherapy is effectively used as curative treatment, in single modality or within a multidisciplinary approach including surgery (PCa) and/or chemotherapy (HNCa). Prediction and reduction of radio-induced side effects are becoming a priority: for PCa, high survival rates should be accompanied by a very low rate of moderate/severe toxicities; for HNCa, there is the need to tailor radiation dose according to disease recurrence risk profile. The shared aim of both cancers is to balance the improvement in outcome with a well-tolerated toxicity profile.

Recent research indicates that the intestinal/salivary bacteria are strongly suspected of being very important in mediating the response to inflammation and lesions. Although their balance deeply changes during radiotherapy, studies done so far in the field of the microbiota-host relationship in radiotherapy have not addressed their role in insurgence of radiation toxicity.

In this study, the investigators will assess how microbial populations evolve and how this influences the host and radiation induced toxicity in a significant number of patients. Moreover, the individual response at the tissue microstructure level, through analysis of images with advanced bioengineering techniques, will be determined.

Results from this research, besides suggesting new ways to predict patients at risk of relevant side-effects, may also suggest possible treatments to change the baseline microbiota of patients at high risk or to modify it during therapy, in order to mitigate toxicity. Understanding the microbiota-radiotherapy interaction may thus lead to novel, effective and inexpensive ways of assessing and managing complications of cancer treatment.


Condition or disease Intervention/treatment
Prostate Cancer Head and Neck Cancer Radiation: External beam radiotherapy for prostate cancer Radiation: External beam radiotherapy for head and neck cancer

  Show Detailed Description

Study Type : Observational
Estimated Enrollment : 400 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Microbiota, Inflammatory Environment, Clinical and Radiomic Features as Predictors of Normal Tissue Response in Radiotherapy for Prostate and Head-and-neck Cancer
Actual Study Start Date : February 2, 2017
Estimated Primary Completion Date : July 31, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
PCa patients - Discovery cohort
External beam radiotherapy for prostate cancer
Radiation: External beam radiotherapy for prostate cancer
Patients will receive radiotherapy for prostate cancer and possible adjuvant hormone therapies as foreseen by international guidelines. No modification of standard regimens is considered. PCa patients are treated with 78 Gy, 2Gy/fraction, in exclusive setting and with 70 Gy, 2Gr/fraction in the post-prostatectomy setting. Lymph node irradiation is performed (50 Gy, 2Gy/fraction) when indicated by risk class.

HNCa patients - Discovery cohort
External beam radiotherapy for head and neck cancer
Radiation: External beam radiotherapy for head and neck cancer
Patients will receive radiotherapy for head and neck cancer and possible concomitant chemotherapies as foreseen by international guidelines. No modification of standard regimens is considered. In curative setting, HNCa patients are treated at a total dose of 70 Gy, 59.4 Gy and 56.1 Gy in 33 fractions to high risk Planning Target Volume (PTV), intermediate risk and low risk PTV, respectively. In high risk post-operative setting they are treated with 66 Gy (according to histopathological features), 60 Gy and 56.1 Gy to high, intermediate and low risk PTV, respectively; while, in intermediate risk post-operative case, intermediate and low risk PTV are irradiated with 60 Gy and 54 Gy, respectively. Chemotherapy will be platinum based (weekly or 3-weekly cisplatin).

PCa patients - Validation cohort
External beam radiotherapy for prostate cancer
Radiation: External beam radiotherapy for prostate cancer
Patients will receive radiotherapy for prostate cancer and possible adjuvant hormone therapies as foreseen by international guidelines. No modification of standard regimens is considered. PCa patients are treated with 78 Gy, 2Gy/fraction, in exclusive setting and with 70 Gy, 2Gr/fraction in the post-prostatectomy setting. Lymph node irradiation is performed (50 Gy, 2Gy/fraction) when indicated by risk class.

HNCa patients - Validation cohort
External beam radiotherapy for head and neck cancer
Radiation: External beam radiotherapy for head and neck cancer
Patients will receive radiotherapy for head and neck cancer and possible concomitant chemotherapies as foreseen by international guidelines. No modification of standard regimens is considered. In curative setting, HNCa patients are treated at a total dose of 70 Gy, 59.4 Gy and 56.1 Gy in 33 fractions to high risk Planning Target Volume (PTV), intermediate risk and low risk PTV, respectively. In high risk post-operative setting they are treated with 66 Gy (according to histopathological features), 60 Gy and 56.1 Gy to high, intermediate and low risk PTV, respectively; while, in intermediate risk post-operative case, intermediate and low risk PTV are irradiated with 60 Gy and 54 Gy, respectively. Chemotherapy will be platinum based (weekly or 3-weekly cisplatin).




Primary Outcome Measures :
  1. Acute toxicity [ Time Frame: <90 days after radiotherapy ]
    If any, acute (<within 90 days from radiotherapy completion) Grade 1, Grade 2, Grade 3-4 disorder, according to the Common Terminology Criteria for Adverse Events (CTCAE) grading system, and its association with clinical variables, absorbed dose, microbioma characteristics and radiomic features.


Secondary Outcome Measures :
  1. Late toxicity [ Time Frame: 3 months - 3 years after radiotherapy ]
    If any, late (> 90 days after radiotherapy completion) Grade 1, Grade 2, Grade 3-4 disorder, according to the Common Terminology Criteria for Adverse Events (CTCAE) grading system, and its association with clinical variables, absorbed dose, microbioma characteristics and radiomic features.


Biospecimen Retention:   Samples With DNA
Whole blood samples of all patients, stool samples of prostate cancer patients, salivary samples of head and neck cancer patients


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients undergoing external beam radiotherapy for prostate or head and neck cancer at the Radiation Oncology 1 and Radiation Oncology 2 units of the Istituto Nazionale dei Tumori.
Criteria

Inclusion Criteria (PCa patients in discovery and validation cohorts):

  • Patients with histologically confirmed diagnosis of PCa candidate to exclusive or post-surgical radiotherapy, in both case it can be associated to hormone therapy
  • Prognostic risk included in the very low, low, intermediate or high risk classes following the NCCN Clinical Practice Guidelines in Oncology and patients with oligometastatic disease treated with curative doses to the prostate (≥70 Gy at 2 Gy per fraction)
  • Written informed consent to the study

Exclusion Criteria (PCa patients in discovery and validation cohorts):

  • Previous pelvic radiotherapy
  • Autoimmune disease (scleroderma,Chron's disease and ulcerative colitis), chronic kidney disease requiring dyalis
  • Patients with malignant neoplasm in treatment with local or systemic therapies, except for patients with PCa and skin cancers
  • Refusal to accept the study participation modalities

Inclusion Criteria (HNCa patients in discovery and validation cohorts):

  • ECOG PS ≤ 3
  • Histologically confirmed diagnosis of squamous cell carcinoma of the head and neck (oral cavity, pharynx, larynx, paranasal sinuses and nasal cavity, salivary glands)
  • Non-metastatic stage III-IV cancer of the pharinx, larynx according to AJCC VII edition. Patients with stage III-IV cancer of salivary glands o paranasal sinuses. Patients with stage I-II cancer of pharinx and larynx only if neck lymph nodes or oral mucosa are included in the irradiated volume
  • Indication to exclusive or post-surgical radiotherapy (associated or not to systemic therapy according to internal guidelines)
  • Written informed consent to the study

Exclusion Criteria (HNCa patients in discovery and validation cohorts):

  • Previous head and neck radiotherapy
  • Connective tissue disease (lupus erythematosus or scleroderma) or other concomitant head and neck cancers, except for in situ skin cancers not requiring radiotherapy or systemic therapies.
  • Refusal to accept the study participation modalities

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03294122


Contacts
Contact: Riccardo Valdagni, MD, PhD +0039 02-23903034 riccardo.valdagni@istitutotumori.mi.it
Contact: Tiziana Rancati, MS +0039 02-23903786 tiziana.rancati@istitutotumori.mi.it

Locations
Italy
Fondazione IRCCS Istituto Nazionale Tumori Recruiting
Milan, Italy, 20133
Contact: Riccardo Valdagni, MD, PhD    +39 02-23903034    riccardo.valdagni@istitutotumori.mi.it   
Contact: Tiziana Rancati, MS    +39 02-23903786    tiziana.rancati@istitutotumori.mi.it   
Principal Investigator: Riccardo Valdagni, MD, PhD         
Sponsors and Collaborators
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Investigators
Principal Investigator: Riccardo Valdagni, MD, PhD Fondazione IRCCS Istituto Nazionale dei Tumori
Study Director: Ester Orlandi, MD Fondazione IRCCS Istituto Nazionale dei Tumori
Study Director: Nice Bedini, MD Fondazione IRCCS Istituto Nazionale dei Tumori
Study Director: Loris De Cecco, PhD Fondazione IRCCS Istituto Nazionale dei Tumori
Study Director: Nadia Zaffaroni, PhD Fondazione IRCCS Istituto Nazionale dei Tumori
Study Director: Tiziana Rancati, MS Fondazione IRCCS Istituto Nazionale dei Tumori
  Study Documents (Full-Text)

Documents provided by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano:
Informed Consent Form  [PDF] December 20, 2016


Publications:

Responsible Party: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
ClinicalTrials.gov Identifier: NCT03294122     History of Changes
Other Study ID Numbers: INT 11/17
First Posted: September 26, 2017    Key Record Dates
Last Update Posted: October 3, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano:
Radiotherapy
Adverse effects
Prostate cancer
Head and neck cancer
Patient risk stratification
Mathematical models
Microbiome
Inflammatory cytokines
Magnetic Resonance Imaging

Additional relevant MeSH terms:
Prostatic Neoplasms
Head and Neck Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases