Neoplasms

Digestive System Diseases

All Conditions

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

preoperative short-course radiotherapy(5×6Gy) followed by 4×mFOLFOX6 chemotherapy

preoperative short-course radiotherapy(5×7Gy) followed by 4×mFOLFOX6 chemotherapy

preoperative short-course radiotherapy(5×8Gy) followed by 4×mFOLFOX6 chemotherapy

Patients will be enrolled into Group 1 to 3 according to the time order of entering the study to receive dose from 6Gy×5F to 8Gy×5F using the traditional 3+3 dose escalation design.

preoperative short-course radiotherapy

Benhua Xu

Mengxia Zhang

Preoperative radiotherapy followed by total mesorectal excision (TME) has been recommended as the preferred treatment method for locally advanced rectal cancer. Similar rates of local control, survival and toxicity were observed in preoperative long-course radiotherapy (LCRT) (45-50.4 Gy in 25-28 fractions) and short-course radiotherapy (SCRT) of 25 Gy in five fractions. For the convenience of SCRT, a growing number of patients tend to receive SCRT as preoperative radiotherapy. Although SCRT can shorten treatment interval and cut down the cost of treatment, it's pathological complete response (pCR) rate is relatively low (SCRT vs. LCRT: 0.7% vs. 16%). Hence, the optimal pattern of preoperative therapy of locally advanced rectal cancer still deserves to be explored. Previous studies have confirmed the feasibility and safety of 30Gy/5 fractions in SCRT of rectal cancer and verified that SCRT followed by mFOLFOX6 chemotherapy can improve the pCR rates. Therefore, investigators aimed to establish a dose escalation mode of SCRT (5×6Gy/7Gy/8Gy) followed by four cycles of modified FOLFOX6(mFOLFOX6) chemotherapy to test the safety and efficacy in treating locally advanced rectal cancer.

Rectal cancer is one of the most common malignant tumors in western countries and its incidence and mortality rates have been ascending for several decades in our country. Surgical resection is the primary treatment method for resectable tumor. Post-operative chemo-radiotherapy can improve local control but can also lower the tolerance rate and increase the incidence of postoperative complications. It is generally not recommended as a regular treatment method excepting the patients who have high risk factors of recurrence after surgery. Preoperative radiotherapy followed by total mesorectal excision(TME) has been recommended as a preferred treatment regimen for locally advanced rectal cancer for it is more effective in local control compared with that of postoperative radiotherapy. The traditional long-course radiotherapy(LCRT) is 45-50.4 Gy in 25-28 daily fractions given with concurrent chemotherapy and delayed surgery(4-8 weeks after chemo-radiotherapy). Also considered an alternative treatment option is preoperative short-course radiotherapy(SCRT) of 25 Gy in five daily fractions and followed by immediate surgery(1 week after SCRT). Similar rates of local control, survival and toxicity were observed in these two regimens. Although SCRT can reduce treatment interval and cut down costs, it's pathological complete response(pCR) rates are relatively low. Bujko et al. reported that the pCR rate for LCRT and SCRT are 16% and 0.7%, respectively. This difference may partially related to the interval between preoperative radiotherapy and surgery. The pCR rates are higher in patients who have the longer interval. In the latest multicenter, randomized, non-blinded, phase III, non-inferiority trial(Stockholm III), participants were randomly assigned to receive either 5×5 Gy radiation dose with immediate surgery within 1 week(SCRT) or after 4-8 weeks(SCRT with delay) or 25×2 Gy radiation dose followed by surgery after 4-8 weeks(LCRT with delay). All these regimens show similar oncological results. However, LCRT with delay prolongs the treatment interval substantially. Although radiation-induced toxicity was observed after SCRT with delay, postoperative complications were significantly reduced compared with that of SCRT followed by immediate surgery. Thus, SCRT with delay to surgery is a useful alternative to conventional SCRT with immediate surgery.

The optimal pattern of dose fractionation of preoperative radiotherapy still deserves to be explored. J Widder et al. reported that SCRT of 25 Gy administered within 1 week of 2.5 Gy twice daily for resectable rectal cancer generates a well-tolerated and simple way to increase local control. A prospective phase II study of SCRT for rectal cancer with twice daily fractions of 2.9 Gy to a total dose of 29 Gy also results in tolerable toxicity and favourable local control. Although both of the modifications of SCRT have acceptable toxicity and well local control, the improvement in overall survival is still limited. Investigators suppose that whether escalating single radiation dose of SCRT (6Gy,7Gy,8Gy...) may further improve local control and overall survival with tolerable toxicity. A prospective phase II study of SCRT that made a boost to the gross tumor volume(GTV) up to a total of 30 Gy in five fractions to investigate the feasibility and the rate of complete pathological response. The results demonstrated that acceptable toxicity and a better rate of pCR can be achieved. Studies have confirmed that high pCR rates were beneficial to survival. Hence, investigators consider that it is feasible to escalate single radiation dose of SCRT in treating rectal cancer. The theoretical basis of escalation of single radiation dose of SCRT may improve survival outcome are as follows:

1. To improve the biological equivalent doses(BED) of the tumor Biological equivalent doses (BED) were used for comparison of various fractionations of radiotherapy and were calculated with the formula for late normal tissue toxicity BED (Gy) =nd\[1 +(d /α / β)\] n: number of fractions d: single fraction dose (Gy) α/β: take 3 Gy for normal tissues According to the formula, BED is determined by n, d and α/β. This suggests that escalation of fractional dose can significantly increase BED of tumor, thus can amount to the greater kill to tumor cells.
2. To induce tumor immune response Several studies reported that radiotherapy can induce or regulate immune response, which can suppress tumor growth and generate inflammatory response. Field radiotherapy can motivate the radiation effects of local-regional and distant area of the body.

The other one criticism in treating rectal cancer is distant metastasis that hinder the improve of overall survival. Preoperative chemotherapy can play a role in controlling the potential micrometastases. Previous studies have confirmed that SCRT followed by mFOLFOX6 chemotherapy can improve the pCR rates. Therefore, in this Phase I Study, the safety and efficacy will be tested using a dose escalation mode of SCRT (5×6Gy/7Gy/8Gy) followed by four cycles of mFOLFOX6 chemotherapy when treating locally advanced rectal cancer.

Dose Escalation Methods in Phase I Cancer Clinical Trials:

Three patients receive the lowest level of radiation dose in a cohort and dose limited toxicity(DLT) is observed. If none of the patients show DLT, another cohort of three patients receive the next higher level of dose. If not, a further cohort of three patients will receive the same dose when one or more patients exhibit DLT. Of the six patients treated at this dose level, the trial continues at the next dose level if only one out the six patients appears DLT and stops at that dose level if at least two patients appear DLT. When the escalation stopped, additional three patients will be required at this dose level. The maximum sample size will depend on the dose level that is in progress.

Short-course Radiotherapy (5×6Gy/7Gy/8Gy) Followed by Neo-adjuvant Chemotherapy for Locally Advanced Rectal Cancer

Phase I Trial of Dose-escalation Preoperative Short-course Radiotherapy (5×6Gy/7Gy/8Gy) Followed by Neo-adjuvant Chemotherapy in Locally Advanced Rectal Cancer : the FJUHR-01 Trial

According to pathological response criteria, a total regression is considered a complete response.

According to the pathological outcomes after received surgery.

Surgical complications are defined as those occurring within 30 days after surgery, such as re-operation, anastomotic fistula, bleeding, infection and death related to the operation.

Number of participants with abnormal laboratory values and/or adverse events that are related to radiation or chemotherapy as assessed by Common Toxicity Criteria for Adverse Effects(CTCAE) v4.0.

Fujian Medical University Union Hospital

Director,Radiation Oncology

Participants with certain types of cancers that are eligible for studies at Memorial Sloan-Kettering Cancer Center.

Your appointment with your doctor will be audio taped. The research team will listen to the tape(s) and type them up. The team will then look for patterns in the discussions between patients and doctors. They will use this information to see if the discussions can be improved.

Consult visit

Richard Brown, PhD

The purpose of this study is to examine doctor-patient communication about treatment options which may include an experimental, new treatment for cancer. What we learn from this study may help us to teach doctors better ways to talk to their patients.

Subjects will be cancer patients attending one of three outpatient clinics at Memorial Sloan-Kettering Cancer Center. Subjects will be recruited from the Melanoma/Sarcoma, GI and Genitourinary Oncology services. The patients of six oncologists across the three services will be approached. All patients of these six oncologists who are invited to participate in a Phase I clinical trial will be approached to participate in the study. Patients who consent to participate in this study will be included in the sample regardless of their trial decision.

Design and Analysis:

To gather information about the communication strategies used by oncologists to discuss trials, a qualitative analysis of audio recordings of consultations containing discussions of Phase I trials will be conducted. These consultations will be audio recorded and transcribed in full; analysis will proceed using the constant comparative method. Initially (and as is consistent with the qualitative method employed for this study), a small sample of 15 patients will be recruited. Once an exhaustive analysis of this original data set is complete a further set of 15 patients will be recruited and transcripts of these consultations analyzed. In order to identify any new themes, the themes that emerged from the new data set will be compared with those identified in the original data set. We anticipate that the study will be completed within one year of commencement.

Significance: Oncologists report that one of their most significant communication challenges is communicating effectively and ethically with their patients about joining a clinical trial. Communication skills training has demonstrated efficacy in assisting doctors in this difficult task, however, there is a paucity of research in this area and studies have been limited to the Phase II and III trial setting. There is some research evidence that suggests that different communication issues and challenges emerge in the Phase I versus the Phase II and III trial setting. The pilot research proposed in this protocol will: a) explore the types of communication currently used by oncologists when recruiting patients to clinical trials and b) develop a set of communication strategies that can be used to address gaps in doctor- patient communication in this difficult area.

Seeking Informed Consent to Phase I Cancer Clinical Trials: Identifying Oncologists'Communication Styles

Seeking Informed Consent to Phase I Cancer Clinical Trials: Identifying Oncologists' Communication Styles

Memorial Sloan Kettering Cancer Center

Brown, Richard, PhD

Nervous System Diseases

Rare Diseases

Glioma

Diffuse Intrinsic Pontine Glioma

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Exablate MR Guided Focused Ultrasound for Blood Brain Barrier Disruption with Doxorubicin for treating pediatric patients with DIPG

Blood Brain Barrier Disruption (BBBD) via Exablate Type 2 system with microbubble resonators on the day of Doxorubicin infusion to treat DIPG brain tumors

Exablate

Nadir Alikacem

Elizabeth Paronett

Roger Packer

Robert Keating

Toba Niazi, MD

Ana Diaz, ARNP

The purpose of this study is to evaluate the safety and efficacy of targeted blood brain barrier disruption with Exablate Model 4000 Type2.0/2.1 in combination with Doxorubicin therapy for the treatment of DIPG in pediatric patients

This is a prospective, single arm, non-randomized feasibility study to evaluate the safety, feasibility and preliminary efficacy of Blood Brain Barrier Disruption (BBBD) using the Exablate Type 2 system in pediatric patients with Diffuse Intrinsic Pontine Gliomas (DIPG)undergoing Doxorubicin chemotherapy. The study will be conducted at up to three sites in the United States. Patients will undergo 3 treatment cycles, approximately 4 -6 weeks apart. The study aims to establish feasibility and safety of Exablate BBBD in conjunction with Doxorubicin in the treatment of pediatric DIPG and assess preliminary efficacy in this patient population.

Blood Brain Barrier (BBB) Disruption Using Exablate Focused Ultrasound With Doxorubicin for Treatment of Pediatric DIPG

A Safety and Feasibility Study to Evaluate Blood Brain Barrier Disruption Using Exablate MR Guided Focused Ultrasound in Combination With Doxorubicin in Treating Pediatric Patients With Diffuse Intrinsic Pontine Gliomas (DIPG)

PFS will be assessed based on the Response Assessment in Pediatric Neuro-Oncology (RAPNO) scale.

All adverse events from first treatment to end of study will be documented and reported according to the CTCAE terminology and severity scale

BBBD will be assessed as a comparative ratio measured in pre and post-sonication contrast-enhanced MR images

InSightec

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Osteosarcoma

Sarcoma

Neoplasm Metastasis

Neoplastic Processes

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Bone Density Conservation Agents

Micronutrients

Hematinics

Vitamins

Cyclophosphamide

Methotrexate

Sirolimus

Zoledronic Acid

Temsirolimus

MTOR Inhibitors

Antimetabolites

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Clotrimazole

Miconazole

Antifungal Agents

Folinic Acid

Folate

Vitamin B9

Drug : Metronomic Cyclophosphamide, Methotrexate, Sirolimus, Zoledronic acid Assessment of the maximum tolerated dose of sirolimus Cyclophosphamide, Methotrexate and Sirolimus will be administrated orally. Zoledronic Acid will be administrated by infusion (IV).

Cyclophosphamide, Methotrexate and Sirolimus will be administrated orally. Zoledronic Acid will be administrated by infusion (IV).

Trial based on a dose escalating study design assessing two dose levels of sirolimus when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) followed by an expansion cohort once the MTD is established.

Sirolimus combined with CP, MT and ZA

Maud TOULMONDE, Doctor

This is a prospective open-labeled phase I trial based on a dose escalating study design assessing two dose levels of sirolimus when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) followed by an expansion cohort once the Maximum Tolerated Dose (MTD) is established.

The dose escalation part of the trial will be concerned on adults with advanced solid tumor with bone metastasis and young and adult patients with unresectable locally advanced or metastatic osteosarcoma.

The Expansion cohort will be conducted on young and adult patients with unresectable locally advanced or metastatic osteosarcoma.

Metronomic Chemotherapy in Patients With Advanced Solid Tumor With Bone Metastasis and Advanced Pretreated Osteosarcoma

Metronomic Cyclophosphamide and Methotrexate Combined With Zoledronic Acid and Sirolimus in Patients With Advanced Solid Tumor With Bone Metastasis and Advanced Pretreated Osteosarcoma. A Phase Ib Study From the French Sarcoma Group

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Short-course Radiotherapy (5×6Gy/7Gy/8Gy) Followed by Neo-adjuvant Chemotherapy for Locally Advanced Rectal Cancer	NCT03466424	Radiation Oncol... Rectal Cancer	preoperative sh...	18 Years - 70 Years	Fujian Medical University Union Hospital
Seeking Informed Consent to Phase I Cancer Clinical Trials: Identifying Oncologists'Communication Styles	NCT00582192	Cancer	Consult visit	18 Years -	Memorial Sloan Kettering Cancer Center
Blood Brain Barrier (BBB) Disruption Using Exablate Focused Ultrasound With Doxorubicin for Treatment of Pediatric DIPG	NCT05630209	Brain Tumor	Exablate Doxorubicin	5 Years - 21 Years	InSightec
Metronomic Chemotherapy in Patients With Advanced Solid Tumor With Bone Metastasis and Advanced Pretreated Osteosarcoma	NCT02517918	Solid Tumor Osteosarcoma	Sirolimus combi...	13 Years -	Institut Bergonié
Seeking Informed Consent to Phase I Cancer Clinical Trials: Identifying Oncologists'Communication Styles	NCT00582192	Cancer	Consult visit	18 Years -	Memorial Sloan Kettering Cancer Center

Spots Global Cancer Trial Database for phase i trial