Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Neoplastic Processes

patients in the observation arm receive no adjuvant local radiation therapy after complete surgical resection of a cerebral metastasis

patients in the intervention arm receive an adjuvant local radiation therapy (cavity boost radiation therapy: 10 x 3 Gy ad 30 Gy; clinical target volume (CTV): resection cavity plus surrounding 5 mm; planning target volume (PTV): CTV + 1mm)

Cavity boost radiation therapy with 10 x 3 Gy for patients suffering from complete resected cerebral metastases

Cavity boost radiation

Marcel A. Kamp, MD

Michael Sabel, Prof. Dr.

Wilfried Budach, Prof. Dr.

The purpose of this study is to determine whether a local fractionated radiation therapy achieves a better local tumor control after complete surgical metastases resection at 6 month as compared to observation alone. Further it should be evaluated if cognitive functioning and quality of life is similar in both groups.

The surgical resection of cerebral metastases as a key element in a multimodal therapeutic concept of brain metastatic patients is included in the common recommendations and international guidelines (level I evidence). These recommendations are based on a series of prospective, randomized and controlled studies which addressed the impact of the surgical metastases resection combined with a whole-brain radiation therapy (WBRT) in comparison to WBRT alone. Achieving local tumor control is the major goal of surgery and local tumor control rate after surgery alone has been addressed in few studies: A prospective, randomized American multicenter study revealed a local recurrence rate of 46% by median follow-up of 43 weeks for patients who underwent surgery alone without an adjuvant radiation therapy. Similarly, the 2-year local recurrence rate after metastases resection alone was 53.1% in a retrospective Korean study and 59% in the prospective, randomized and controlled EORTC 22952-26001 study.

In conclusion, standard surgery alone is not sufficient to achieve local control in about 50% of patients (evidence level I). Therefore, surgery of cerebral metastases is often followed by an adjuvant radiation therapy, which is an important part of a multi-modal therapy. Evidence for an additional adjuvant whole-brain radiation therapy (WBRT) after surgical resection was gained from a first prospective, randomized study in 1998: Patients treated by surgery followed by adjuvant WBRT had a significant lower local in-brain progression rate as compared to patients randomized to surgery alone (46% with a median follow-up of 48 weeks in the observation group vs. 10% with a median follow-up of 43 weeks). This result was recently confirmed by the EORTC 22952-26001 study: The 2-year local in-brain progression rate after surgical resection was reduced by a WBRT from 59% to 27%. But despite the lower local and also lower distant in-brain progression rate, the WBRT had no significant influence on the overall survival. The additional analysis of the quality of life data of the EORTC 22952-26001 study showed, that a WBRT negatively impacts the health-related quality of life with a statistically relevant and clinically significant impairment of the physical functioning (at 8 weeks), cognitive functioning and of the global health status. In conclusion, WBRT after surgery of cerebral metastases significantly reduces the incidence of local recurrences but has no impact on the overall survival and has a significant negative impact on the patient´s quality of life and cognitive function. Therefore, WBRT is not mandatory as adjuvant concept after surgical metastases resection and does not have an additional oncological impact in comparison to observation.

A local fractionated radiation therapy in analogy to the WBRT might achieve a similar local tumor control than observation alone but might be associated with an improved cognitive functioning as compared to WBRT. The purpose of this study is to determine whether a local fractionated radiation therapy achieves a better local tumor control after complete surgical metastases resection at 6 month as compared to observation alone. Further it should be evaluated if cognitive functioning and quality of life is similar in both groups.

Cavity Boost Radiation Therapy vs. Observation in Cerebral Metastases After Complete Surgical Resection

Primary outcome measure is the local tumor control of resected metastases after local cavity boost radiation therapy or observation at 6 month

Secondary outcome measure is the local tumor control of resected metastases after local cavity boost radiation therapy or observation at 12 and 18 month

Secondary outcome measure is the distant tumor control at 6, 12 and 18 month

Secondary outcome measure is the incidence of a leptomeningeal carcinosis at 6, 12 and 18 month

Secondary outcome measure is the patients quality of life at 3, 6, 9 12, 15, 18 month as assessed by the Eortc qlq bn20 questionaire

Secondary outcome measure is the patients quality of life at 3, 6, 9, 12, 15 and 18 month as assessed by the Eortc qlq c30 questionaire

Secondary outcome measure is the patients neurocognitive functioning at 3, 6, 9 12, 15 and 18 month as assessed by the MMSE

Secondary outcome measure is the patients neurocognitive functioning at 3, 6, 9, 12, 15 and 18 month as assessed by the Hopkins Verbal Learning Test (HVLT),

Secondary outcome measure is the patients neurocognitive functioning at 3, 6, 9 12, 15 and 18 month as assessed by the Controlled Oral Word Association (COWA)

Secondary outcome measure is the patients neurocognitive functioning at 3, 6, 9 12, 15 and 18 month as assessed by the Test and Trail-Making Test (TMT) A \& B

Heinrich-Heine University, Duesseldorf

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Neoplasm, Residual

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Gemcitabine

Carboplatin

Pemetrexed

Cisplatin

Immunomodulating Agents

Nivolumab

Antimetabolites

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

All participants will have blood taken for ctDNA testing.

A cycle is 21 days. Pemetrexed (for participants with non-squamous non-small cell lung cancer), intravenously (by vein) on Day 1 of Cycles 1-4, OR gemcitabine (for all other participants) on Days 1 and 8 of Cycles 1-4.

Cisplatin\*, intravenously (by vein) on Day 1 of Cycles 1-4 Nivolumab, intravenously (by vein) on Day 1 of Cycles 1-4

\*If cisplatin is not tolerated, carboplatin may be given instead

All participants will have blood taken for ctDNA testing.

Participants will be followed as per standard of care every 3 months.

Blood will be collected for ctDNA testing

ctDNA blood test

Natasha Leighl, M.D.

Natasha Leighl

This is a study to look at whether the presence of circulating tumour DNA (ctDNA) in the blood can help to predict whether giving adjuvant treatment after surgery can decrease the chance of the cancer coming back in people with lung cancer.

For people who have early stage non-small cell lung cancer (NSCLC), the usual treatment is surgery. For many people, surgery is enough to get rid of all the cancer. However, for some people, there may be a little bit of cancer remaining. If there is some cancer left over, it may lead to the cancer regrowing. This is called relapse.

Many cancers shed little bits of their DNA (deoxyribonucleic acid, molecules that contain instructions for how cells develop and function) into the bloodstream. A blood test can be used to test for the amount of circulating tumour DNA (ctDNA). Some studies have shown that the presence of ctDNA in the blood may predict cancer recurrence.

The purpose of this research study is to see if adjuvant treatment (additional treatment given after primary treatment) can help decrease the risk of the cancer recurring in people with lung cancer who have ctDNA detected in their blood after surgery.

Using ctDNA to Determine Therapies for Lung Cancer

From Liquid Biopsy to Cure: Using ctDNA Detection of Minimal Residual Disease to Identify Patients for Curative Therapy After Lung Cancer Resection

Bristol-Myers Squibb

University Health Network, Toronto

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Rare Diseases

Wilms Tumor

Neoplasms by Histologic Type

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Syndrome

Neoplastic Syndromes, Hereditary

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Genetic Diseases, Inborn

Wilms' Tumor

Favorable Histology Stage I \& II and FH Stage III/IV Delayed Local Control with clear surgical margins and pathologically negative lymph nodes. Participants will undergo complete surgical resection at diagnosis or after 6-12 weeks of induction chemotherapy.

Participants will undergo surgical resection at diagnosis or after 6-12 weeks of induction chemotherapy. Those with evidence of LN involvement, surgical margin involvement, local or diffuse spill, gross disease in the renal bed or peritoneal implants, will receive adjuvant PBRT.

Participants will undergo partial nephrectomy after 6-12 weeks of induction chemotherapy. Those with evidence of LN involvement, surgical margin involvement, local or diffuse spill, gross disease in the renal bed or peritoneal implants, will receive adjuvant PBRT

The treatment approach with radiation therapy prescribed in this trial is designed to deliver highly conformal radiation therapy (proton beam radiation or intensity modulated photon radiation) to target volumes that are based on the burden of disease.

Proton Beam Radiation (PBRT)

Patients will receive standard of care chemotherapy based on diagnosis and stage.

DD-4A Chemotherapy Regimen

Participants will undergo complete surgical resection at diagnosis or after 6-12 weeks of induction chemotherapy

Complete Surgical Resection

Participants will undergo surgical resection at diagnosis or after 6-12 weeks of induction chemotherapy.

Surgical Resection

Participants will undergo partial nephrectomy after 6-12 weeks of induction chemotherapy.

Partial Nephrectomy

Matthew J Krasin, MD

Participants are being asked to take part in this clinical trial, a type of research study, because the participants have a Wilms Tumor cancer.

Primary Objectives

To determine whether delivery of proton beam radiation to a conformal reduced target volume in the flank allows normal flank growth compared to the contralateral untreated side and non-irradiated patients.

Secondary Objectives

To deliver proton beam radiation to a conformal reduced target volume (partial kidney proton beam radiation therapy) in the affected kidney(s) for patients with Stage V (bilateral Wilms tumor) and specific involved surgical margins yielding no reduction in the high control rates seen with more traditional flank / whole kidney fields.

Exploratory Objectives

* Study the feasibility of sparing the residual kidney, spine and liver in patients requiring whole abdomen radiation therapy using either a proton beam treatment technique or intensity-modulated radiation therapy ( IMRT) photon based technique.
* Study the feasibility of delivering whole lung radiation therapy with proton beams with the goals of sparing the developing breast tissue, heart structures, thyroid and liver.
* Develop simultaneous xenografts and organoid models from the same starting material to study Wilms tumor biology and compare responses to chemotherapeutic agents.
* Define the evolution of organ specific (kidney, liver, pancreas, etc.) abnormalities (laboratory studies) as an early marker of possible late end organ damage and their relationship to radiation.
* Study and evaluate impact of proton therapy on the musculoskeletal system and physical performance and compare with photon therapy cases treated with classical treatment fields.
* Assess CTC-AE and Pediatric Patient Reported Outcomes during radiation and in follow-up, correlating with disease, treatment and patient variables.
* Correlate quantitative MRI values, including apparent diffusion coefficient (ADC) values, with histopathology findings post-surgery in children with (bilateral) Wilms.
* Assess daily variations in proton range along each treatment beam using standard pre-treatment cone beam CT or on-treatment MR.

Participants will receive proton beam radiation therapy (PBRT) according to stage and surgical findings.

Favorable Histology Stage I \& II and FH Stage III/IV Delayed Local Control with clear surgical margins and pathologically negative lymph nodes: Participants will undergo complete surgical resection at diagnosis or after 6-12 weeks of induction chemotherapy. PBRT will not be administered to the primary site in those with no evidence of spill, peritoneal involvement, lymph node (LN) involvement or microscopic residual in the abdomen. Systemic therapy will be delivered in a standard of care manner according to histology and stage.

Stage III \& IV Adjuvant RT: Participants will undergo surgical resection at diagnosis or after 6-12 weeks of induction chemotherapy. Those with evidence of LN involvement, surgical margin involvement, local or diffuse spill, gross disease in the renal bed or peritoneal implants, will receive adjuvant PBRT. Systemic therapy will be delivered in a standard of care manner according to histology and stage.

Stage V Adjuvant RT: Participants will undergo partial nephrectomy after 6-12 weeks of induction chemotherapy. Those with evidence of LN involvement, surgical margin involvement, local or diffuse spill, gross disease in the renal bed or peritoneal implants, will receive adjuvant PBRT. Systemic therapy will be delivered in a standard of care manner according to histology and stage.

Systemic therapy will follow a well-defined standard of care based on Children's Oncology Group (COG) approaches including pre-operative chemotherapy and adjuvant chemotherapy. The intent will be to standardize chemotherapy to ensure a consistent background of standard of care therapy, while not mandating additional data collection beyond the specific trial objectives.

Treatment of Newly Diagnosed Patient's With Wilm's Tumor Requiring Abdominal Radiation Delivered With Proton Beam Irradiation

Multi-Center Trial Sponsored by St. Jude Children's Research Hospital for the Treatment of Newly Diagnosed Patient's With Wilm's Tumor Requiring Abdominal Radiation Delivered With Proton Beam Irradiation

Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.

Half circumference measurement at 3 year from irradiated and unirradiated hemi-abdomen for patients in need of flank radiation

Half circumference measurement at 5 year from irradiated and unirradiated hemi-abdomen for patients in need of flank radiation

Half circumference measurement at 7 year from irradiated and unirradiated hemi-abdomen for patients in need of flank radiation

Half circumference measurement at 10 year from irradiated and unirradiated hemi-abdomen for patients in need of flank radiation

This objective is to investigate whether deliver proton beam radiation to a conformal reduced target volume (partial kidney proton beam radiation therapy) in the affected kidney(s) for patients Stage V (bilateral Wilms tumor) with specific involved surgical margins yielding no reduction in the high control rates seen with more traditional flank / whole kidney fields.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cavity Boost Radiation Therapy vs. Observation in Cerebral Metastases After Complete Surgical Resection	NCT02887651	Cerebral Metast... Surgery	Cavity boost ra...	18 Years -	Heinrich-Heine University, Duesseldorf
Using ctDNA to Determine Therapies for Lung Cancer	NCT04966663	Non Small Cell ... Complete Surgic... Circulating Tum...	Nivolumab Pemetrexed Gemcitabine Cisplatin Carboplatin ctDNA blood tes...	18 Years -	University Health Network, Toronto
Treatment of Newly Diagnosed Patient's With Wilm's Tumor Requiring Abdominal Radiation Delivered With Proton Beam Irradiation	NCT04968990	Wilms Tumor	Proton Beam Rad... DD-4A Chemother... Complete Surgic... Surgical Resect... Partial Nephrec...	-	St. Jude Children's Research Hospital
Using ctDNA to Determine Therapies for Lung Cancer	NCT04966663	Non Small Cell ... Complete Surgic... Circulating Tum...	Nivolumab Pemetrexed Gemcitabine Cisplatin Carboplatin ctDNA blood tes...	18 Years -	University Health Network, Toronto
Treatment of Newly Diagnosed Patient's With Wilm's Tumor Requiring Abdominal Radiation Delivered With Proton Beam Irradiation	NCT04968990	Wilms Tumor	Proton Beam Rad... DD-4A Chemother... Complete Surgic... Surgical Resect... Partial Nephrec...	-	St. Jude Children's Research Hospital

Spots Global Cancer Trial Database for complete surgical resection