Neoplasms

Digestive System Diseases

All Conditions

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Capecitabine

Antimetabolites

After local excision patients will receive additional TME surgery

After local excision. Patients will receive capecitabine 825 mg/m2 twice a day for 5 weeks only on weekdays. This will be combined with 1.8 Gy in 25 fractions with a limited dose only on the mesorectum

Patients will receive capecitabine 825 mg/m2 twice a day for 5 weeks only on weekdays. This will be combined with 1.8 Gy in 25 fractions with a limited dose only on the mesorectum

Adjuvant chemoradiotherapy

Additional TME surgery

capecitabine

Lisanne Smits

Jurriaan Tuynman

J.B. Tuynman, surgeon

Current therapy for early colorectal cancer is radical Total Mesorectal Excision (TME). Colorectal surgical resections are accompanied with high morbidity of up to 33% and 90 days mortality of up to 9% in the fragile elderly patients as is seen in the results of the Dutch Surgical Colorectal Audit (DSCA) of 2013. Additionally, rectal cancer surgery is associated with substantial loss of health related quality of life due to defecation disorders, incontinence, sexual dysfunction and stoma related morbidity. These disadvantages are acceptable when radical surgery is the only option for cure. Advances in technology enabled the development of local excision of early rectal cancer with precise endoluminal microsurgery or local endoscopic excision resulting in a significant decrease in short- and long term morbidity. However current evidence is of inadequate quality to conclude on the oncologic safety of local treatment for early rectal cancer. Imaging can predict outcome and tailors treatment in more advanced cancer but fails in early cancer. Pathological assessment of the excised tumor tissue provides the optimal information on tumor stage, tumor characteristics and tumor differentiation, thereby it enables to predict the risk of recurrence after local treatment alone. For early rectal cancers, with a low risk on recurrence based on favourable tumor characteristics local excision is seen as safe and these patients do not require an additional treatment. However, for patients with early rectal cancer with a higher risk on recurrence based on tumor characteristics there is no consensus on the additional treatment after local excision. According to the National guideline these patients receive a TME procedure. However, for this subgroup of patients local treatment followed by chemoradiotherapy might also be oncological safe. Current evidence is of inadequate quality to be conclusive. For this subgroup of patients with early rectal cancer with high risk tumorcharacteristics the TESAR trial is designed, in which patiens will be randomised after local endoluminal excision between an additional TME-procedure (standard) and adjuvant chemoradiotherapy. Primary endpoint of the study will be local recurrence at 3 three year follow-up.

Rectal Preserving Treatment for Early Rectal Cancer. A Multi-centred Randomised Trial of Radical Surgery Versus Adjuvant Chemoradiotherapy After Local Excision for Early Rectal Cancers

Amsterdam UMC, location VUmc

MD, PhD

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Patients receive standard palliative therapy, if needed, to address symptoms such as tumor ulceration, pain, bulky adenopathy causing arm symptoms, and other similar situations. Therapy may consist of radiotherapy alone, surgery alone, or a combination of both.

Patients undergo surgery comprising breast-conserving therapy (BCT) or total mastectomy according to patient and treating physician preference. Surgery is to occur no later than 10 weeks after completion of 32 weeks of systemic therapy. Free surgical margins must be achieved with re-excision or mastectomy for patients undergoing BCT. After completion of BCT, patients undergo radiotherapy once a day, 5 days per week. Patients who had mastectomy undergo radiotherapy at the discretion of treating physician.

palliative surgery

therapeutic conventional surgery

palliative radiation therapy

radiation therapy

Seema A. Khan, MD

RATIONALE: The primary tumor might be a source of re-seeding of distant sites and therefore elimination of this source of metastasizing cells by early local therapy may be of benefit.

PURPOSE: This randomized phase III trial is studying early surgery to see how well it works compared to standard palliative therapy in treating patients with stage IV breast cancer.

OBJECTIVES:

Primary

* To evaluate whether early local therapy of intact primary disease in patients with Stage IV breast cancer whose disease does not progress during initial optimal systemic therapy, will result in prolonged survival, compared to patients who receive local therapy for palliation only.

Secondary

* To compare the time to uncontrolled chest wall disease between patients who receive early local therapy versus patients who receive palliative local therapy.
* To determine whether there is a difference in health-related quality-of-life (HRQOL) between patients who receive early local therapy versus patients who receive palliative local therapy.
* To determine whether the absolute value of circulating tumor cells (CTC) burden at 6 months following randomization (time +6) will be lower in the palliative therapy arm than in early local therapy arm, and whether this value is inversely related to survival (lower CTC, longer survival).

Exploratory

* To collect tumor and blood specimens for future exploration of the biological interactions between the primary tumor and metastatic lesions and the effect of primary tumor resection.

OUTLINE: This is a multicenter study. Patients are stratified according to hormone receptor and treatment plan (ER+ or PR+, HER2-, endocrine therapy alone vs ER+ or PR+, and HER2-, chemotherapy and/or endocrine therapy vs ER- or PR-, and HER2- vs HER2+), and number of involved organ systems with distant disease (regional nodes in the axillary, supraclavicular, and internal mammary locations are not considered distant sites) (1 vs \> 1). Patients are randomized to 1 of 2 treatment arms in 1:1 ratio.

* Arm I: Patients receive standard palliative therapy, if needed, to address symptoms such as tumor ulceration, pain, bulky adenopathy causing arm symptoms, and other similar situations. Therapy may consist of radiotherapy alone, surgery alone, or a combination of both.
* Arm II: Patients undergo surgery comprising breast-conserving therapy (BCT) or total mastectomy according to patient and treating physician preference. Surgery is to occur no later than 10 weeks after completion of 32 weeks of systemic therapy. Free surgical margins must be achieved with re-excision or mastectomy for patients undergoing BCT. After completion of BCT, patients undergo radiotherapy once a day, 5 days per week. Patients who had mastectomy undergo radiotherapy at the discretion of treating physician.

Patients may undergo blood and tumor tissue sample collection for circulating tumor cells (CTC) burden and future studies.

Patients complete the Functional Assessment of Cancer Therapy - Breast Trial Outcome Index (FACT- TOI) and FACT - General (22) and the Breast Cancer Subscale (FACT-B) quality-of-life questionnaires at baseline and periodically during study.

After completion of study therapy, patients are followed up periodically for 5 years.

Early Surgery or Standard Palliative Therapy in Treating Patients With Stage IV Breast Cancer

A Randomized Phase III Trial of the Value of Early Local Therapy for the Intact Primary Tumor in Patients With Metastatic Breast Cancer

Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive

Overall survival (OS) was defined as time from randomization to death from any cause. All patients will be followed for survival through 5 years. Cases with incomplete follow-up or without record of vital status will be censored at the date of last contact. 3-year OS rate was estimated using Kaplan-Meier method.

For patients in arm II (early local therapy), time to locoregional recurrence was defined as time from randomization to date of locoregional recurrence; for patients in arm A (continued systemic therapy), time to locoregional progression was defined as time from randomization to date of locoregional progression. In this study, locoregional recurrence was defined as the new development or clinically significant increase in size of any supraclavicular, infraclavicular, internal mammary or axillary adenopathy or chest wall disease or invasive in-breast recurrence for patients on arm B; for patients on arm A, locoregional progression was defined as the development of symptoms leading to a decision for local therapy. Locoregional recurrence/progression and distant progression were followed separately in the study, and the occurrence of one did not preclude the other getting reported. 3-year cumulative incidence of locoregional recurrence/progression was estimated.

The Functional Assessment of Cancer Therapy-Breast Trial Outcome Index (FACT-B TOI) was used as the primary HRQL endpoint, measured by the prorated aggregate score of the 24 items from the FACT-B (7 functional well-being, 7 physical well-being, 10 breast cancer specific items). The theoretical range of the prorated aggregate score was 0-96, higher scores indicate better quality of life.

National Cancer Institute (NCI)

Eastern Cooperative Oncology Group

The trial involved standard of care systemic therapies and there could be several options of systemic therapies, adverse events data were not collected in the trial.

Patients receive standard palliative therapy, if needed, to address symptoms such as tumor ulceration, pain, bulky adenopathy causing arm symptoms, and other similar situations. Therapy may consist of radiotherapy alone, surgery alone, or a combination of both.

palliative surgery: Undergo standard palliative surgery

palliative radiation therapy: Undergo standard palliative radiotherapy

Arm I (Continued Systemic Therapy)

Patients undergo surgery comprising breast-conserving therapy (BCT) or total mastectomy according to patient and treating physician preference. Surgery is to occur no later than 10 weeks after completion of 32 weeks of systemic therapy. Free surgical margins must be achieved with re-excision or mastectomy for patients undergoing BCT. After completion of BCT, patients undergo radiotherapy once a day, 5 days per week. Patients who had mastectomy undergo radiotherapy at the discretion of treating physician.

therapeutic conventional surgery: Undergo early surgery

radiation therapy: Undergo radiotherapy

Arm II (Early Local Therapy)

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Study Statistician

3-year Overall Survival Rate

3-year Cumulative Incidence of Locoregional Recurrence/Progression

All randomized patients at step 2 who reported quality of life data at 18 months after randomization

Health-related Quality of Life (HRQL)

Overall Study

Symptoms and General Pathology

Nervous System Diseases

Neoplasm Metastasis

Brain Neoplasms

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Intraoperative Radiotherapy (IORT) administered during surgery

If biopsy is positive, local treatment with IORT will be performed. After IORT (15,40 Gray at 2 mm dept), the applicator will be removed and surgery will be continued in a standard fashion.

Intraoperative Radiotherapy (IORT)

Surgery should be performed according to the local standard of care, preferentially as image-(neuronavigation) guided surgery. To establish the diagnosis of a metastasis and to exclude primary CNS tumors, lymphomas, SCLCs or germinomas it will be performed a peroperative biopsy

Brain surgery

Miquel Macià, MD

Anna Lucas, MD

To evaluate the feasibility and efficacy of the Intraoperative Radiation Therapy (IORT) after the resection of a brain metastases to reduce the incidence of local relapse

IORT After Surgical Resection of Brain Metastases

IORT After Surgical Resection of Brain Metastases: Feasibility and Efficacy Phase II Trial

Time span (in months) between surgery and recurrence within a 0,5 cm margin around the resection cavity, evaluated through Response Assessment in Neuro-Oncology (RANO) criteria for brain metastasis obtained from serial Magnetic resonance imaging (MRI) scans.

The time (in months) from surgery to any progression outside of the 0,5 cm margin around the resection cavity, evaluated through Response Assessment in Neuro-Oncology (RANO) criteria for brain metastasis obtained from serial Magnetic resonance imaging (MRI) scans.

Time (in months) from surgery to any intra- and extracranial tumor progression evaluated through Response Assessment in Neuro-Oncology (RANO) criteria for brain metastasis obtained from serial Magnetic resonance imaging (MRI) scans.

Time (in days) from surgery to the day of initiation of any systemic anti-tumor therapy (e.g., chemotherapy)

Time (in months) from surgery of brain metastases to death by any cause

Assessed by minimal mental scale examination

Assessed by number repetition test (forward and backward)

Assessed by controlled oral word association test

Assessed by European Organization for Research and Treatment (EORTC)- Quality of Life Questionnaires (QLQ C30/BN20)

Assessed by regular neurological examinations combined by serial MRI scans

Institut Català d'Oncologia

The local therapy offered will be determined by the participant's doctor in consultation with the site multidisciplinary team and will be dependent on the size and location of the brain metastases.

Neurosurgery: The surgery may be performed up to 6 weeks before participant being registered on the trial or up to 4 weeks after registration.

Sometimes stereotactic radiosurgery is required to be delivered to the cavity left after the metastasis has been removed (Cavity Boost).

Stereotactic Radiosurgery: Treatment is to commence within 4 weeks of study registration. The size, number and location of the brain metastasis will determine the dose and fractionation schedule of radiotherapy.

Neurosurgery: The decision whether or not to recommend neurosurgery will be made independently of this research study. The complexity and length of the surgery depends on the size and location of the tumour(s).

Stereotactic Radiosurgery: If the participant will be receiving stereotactic radiosurgery (either alone or in combination with neurosurgery), the Radiation Oncologist will organise for the participant to have a Radiotherapy planning. Single metastasis, smaller than or equal to 2cm, may require 1 fraction. Alternately, multiple metastasis, metastasis in the brain stem, or those bigger than 2cm will required multiple fractions to treat. The dose range for the study is 20Gy/1 fraction to 24Gy/3 fractions.

Local Therapy

Claire Phillips, Dr

This study aims to show that brain metastases from Human Epidermal Growth Factor Receptor Type 2 (HER2) positive breast cancers are able to be controlled by local therapies, Stereotactic Radiosurgery (SRS) and/or Neurosurgery (NS), without the need for Whole Brain Radiotherapy (WBRT).

For patients who have Human Epidermal Growth Factor Receptor Type 2 (HER2) positive breast cancer, which has metastasised to the brain, the main treatment options for these brain metastases are Whole Brain Radiotherapy (WBRT), Stereotactic Radiosurgery (SRS) and Neurosurgery (NS).

The purpose of the study is to determine:

1. . How likely the tumours are controlled after treatment with local therapies Neurosurgery (NS) and/or Stereotactic Radiosurgery (SRS).
2. . How likely is it that other tumours develop at new sites in the brain when no Whole Brain Radiotherapy (WBRT) is given.

This study is aiming to recruit 50 participants that have HER2 positive metastatic breast cancer with 1-5 synchronous brain metastases, with at least one metastasis requiring treatment.

The local treatment offered will be determined by the participant's doctor in consultation with the site multidisciplinary team and will be dependent on the size and location of the brain metastases. Each treatment will be performed by the specialist in that field, i.e. neurosurgeon and/or radiation oncologist.

Neurosurgery: The decision whether or not to recommend neurosurgery will be made independently of this research study. The surgery may be performed up to 6 weeks before participant being registered on the trial or up to 4 weeks after registration. The complexity and length of the surgery depends on the size and location of the tumour(s).

Sometimes stereotactic radiosurgery is required to be delivered to the cavity left after the metastasis has been removed (also known as a cavity boost). Timing of Cavity SRS is at the discretion of the treating team. SRS cavity boost must be given after registration and can be given up to 8 weeks after NS resection.

Stereotactic Radiosurgery: If the participant will be receiving stereotactic radiosurgery (either alone or in combination with neurosurgery), the Radiation Oncologist will organise for the participant to have a Radiotherapy planning. Treatment is to commence within 4 weeks of study registration.

The size, number and location of the brain metastasis will determine the dose and fractionation schedule of radiotherapy. Single metastasis, smaller than or equal to 2cm, may require 1 fraction. Alternately, multiple metastasis, metastasis in the brain stem, or those bigger than 2cm will required multiple fractions to treat. The dose range for the study is 20Gy/1 fraction to 24Gy/3 fractions. Each fraction is given on a separate day.

All participants will be followed up at 3 monthly intervals for 12 months after completing their trial treatment (i.e. from the day of their last SRS treatment or neurosurgery, the latter of the two).

At each follow-up visit they will have a clinic visit with the study doctor who to assess any symptoms, record current medications and/or surgeries, monitor their brain metastasis, have a blood test and imaging (CT scan, bone scan and MRI brain).

A Study of Local Therapy for the Treatment of Brain Metastases From HER2 Positive Breast Cancer

A Phase II Study of Local Therapy Only (Stereotactic Radiosurgery and/or Surgery) for Treatment of up to 5 Brain Metastases From HER2 Positive Breast Cancer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Rectal Preserving Treatment for Early Rectal Cancer. A Multi-centred Randomised Trial of Radical Surgery Versus Adjuvant Chemoradiotherapy After Local Excision for Early Rectal Cancers	NCT02371304	Rectal Cancer	Adjuvant chemor... Additional TME ... capecitabine	18 Years -	Amsterdam UMC, location VUmc
Rectal Preserving Treatment for Early Rectal Cancer. A Multi-centred Randomised Trial of Radical Surgery Versus Adjuvant Chemoradiotherapy After Local Excision for Early Rectal Cancers	NCT02371304	Rectal Cancer	Adjuvant chemor... Additional TME ... capecitabine	18 Years -	Amsterdam UMC, location VUmc
Rectal Preserving Treatment for Early Rectal Cancer. A Multi-centred Randomised Trial of Radical Surgery Versus Adjuvant Chemoradiotherapy After Local Excision for Early Rectal Cancers	NCT02371304	Rectal Cancer	Adjuvant chemor... Additional TME ... capecitabine	18 Years -	Amsterdam UMC, location VUmc
Early Surgery or Standard Palliative Therapy in Treating Patients With Stage IV Breast Cancer	NCT01242800	Breast Cancer Stage IV Breast...	palliative surg... therapeutic con... palliative radi... radiation thera...	18 Years - 120 Years	Eastern Cooperative Oncology Group
IORT After Surgical Resection of Brain Metastases	NCT05084092	Brain Neoplasms	Intraoperative ... Brain surgery	18 Years -	Institut Català d'Oncologia
Rectal Preserving Treatment for Early Rectal Cancer. A Multi-centred Randomised Trial of Radical Surgery Versus Adjuvant Chemoradiotherapy After Local Excision for Early Rectal Cancers	NCT02371304	Rectal Cancer	Adjuvant chemor... Additional TME ... capecitabine	18 Years -	Amsterdam UMC, location VUmc
A Study of Local Therapy for the Treatment of Brain Metastases From HER2 Positive Breast Cancer	NCT02898727	Breast Neoplasm...	Local Therapy	18 Years -	Trans Tasman Radiation Oncology Group
IORT After Surgical Resection of Brain Metastases	NCT05084092	Brain Neoplasms	Intraoperative ... Brain surgery	18 Years -	Institut Català d'Oncologia

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