Neoplasms

All Conditions

Rare Diseases

Sarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

This study will examine late effects of treatment for sarcoma (bone and soft tissue cancers) in children. Survival of patients with these diseases has improved over the years, but long-term adverse effects of treatment have also been noted.

Patients previously treated for sarcoma in the NCI's Pediatric Oncology Branch who are in their first remission from sarcoma after completion of therapy and who have had no further cancer treatment (chemotherapy, radiation therapy, cancer related surgery or immunotherapy) for at least 24 months may be eligible for this 3- to 4-day study. It will review the incidence and extent of the following late effects of therapy.

* Heart problems-The chemotherapy drug doxorubicin can cause acute and late injuries to the heart muscle. Patients will undergo magnetic resonance imaging (MRI) of the heart to look for changes and compare the findings with information obtained by standard echocardiogram (ultrasound test of the heart) and by MUGA (nuclear medicine scan of the heart).
* Gonadal dysfunction-The chemotherapy drug cyclophosphamide may affect sex hormone production, leading to infertility, early menopause or brittle bones. Low sex hormone levels may also increase the risk for heart attack, obesity or fracture. Patients will have blood tests to measure hormone levels as well as mineral levels, lipid levels and blood cell counts. They will also have a DEXA scan to measure bone mineral density and a CT scan of the abdomen to evaluate the distribution of fatty tissue in the abdomen. Males will be offered a semen analysis as part of the fertility evaluation.
* Psychosocial problems- Cancer diagnosis and treatment pose a major life stress that can lead to problems with personal relationships, jobs, insurance, education, health care, and personal and professional goal setting. Some patients may become depressed or develop a psychiatric illness. Patients will fill out a questionnaire about their treatment, recovery, and aspects of their current life and will meet with a psychologist and psychiatrist.
* Changes in bodily function and capabilities-Patients who undergo surgery and radiation to treat sarcoma treatment may experience muscle, bone and joint changes. Patients will be interviewed about their performance of daily activities, physical limitations, and changes in skill levels. They will do a series of exercises and will have measurements of strength, mobility and physical skills, focusing on the parts of the body that were affected by the sarcoma and subsequent local therapy.
* Exposure to viruses-A number of patients received blood transfusions as part of their cancer treatment. Some transfusions were given before HIV screening became available. Patients will be tested for this virus as well as the hepatitis virus and HTLV-1 (human T-cell leukemia virus-1), for which there are also small transfusion-associated risks.
* Kidney function-The chemotherapy drug ifosfamide may affect kidney function. Patients will provide a urine specimen for kidney function tests.
* Immune function-Chemotherapy affects the function of infection-fighting immune cells called T-lymphocytes. A blood sample will be drawn for studies of the time involved in recovering full immune function.

Childhood cancers mark a relatively infrequent disease entity with an annual age adjusted rate in children age 0-14 years of 14 per 100,000. Over the last 30 years a striking increase in survival due to improved diagnosis and aggressive treatment approaches has vastly enhanced the outlook in this patient population. 75% of children under 15 years age of can be expected to survive the diagnosis of cancer for more than 5 years. However, reports of improved survival have been followed by increasing awareness of a multitude of long-term treatment-related side effects, in addition to an overall death rate 9.6 times higher than in the sex- and age-matched general population. Over the last 35 years, patients with pediatric sarcomas have been treated in the Pediatric Oncology Branch (POB) of the National Cancer Institute. Since 1971 adriamycin and cyclophosphamide in escalating doses have been incorporated in all multimodality treatment protocols. Ifosfamide became an integral part of therapy in 1986. The survival rate of patients with these diseases has improved over this period of time. Accordingly there exists a group of long-term survivors of therapy employed in a series of POB sarcoma protocols who represent a valuable source of information on treatment-associated late-effects, e.g. cardiotoxicity, gonadal dysfunction, growth delay and stress-related neuroendocrine abnormalities. In addition there may be evaluable rehabilitative impairments and alterations in psychosocial behavior that may only manifest over time, and prove to be characteristic for this population. This protocol will systematically enumerate and describe the incidence and extent of treatment related long-term toxicities in this patient population.

Late Effects of Treatment for Sarcomas in Children

Late Effects of Treatment in Survivors of Pediatric Sarcomas

National Cancer Institute (NCI)

Carcinoma

Neoplasms, Glandular and Epithelial

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Tislelizumab

Oxaliplatin

Antimetabolites

Antineoplastic Agents, Immunological

Combination of Gemox, Donafenib and Tislelizumab

Combination of Gemcitabine, Oxaliplatin, Donafenib and Tislelizumab every 3 weeks

Combination of Gemcitabine, Oxaliplatin, Donafenib and Tislelizumab

Lu Wang, M.D.

Yiming Zhao, M.D.

In this phase 2 study, the investigators aim to evaluate the effects and safety of combined therapy using oxaliplatin and gemcitabine chemotherapy, Donafenib and Tislelizumab for patients with advanced biliary tract carcinoma.

Most advanced biliary tract carcinoma (BTC) patients are often accompanied by local or distant metastases and lose the opportunity for surgical resection. For patients with advanced BTC who have been in stages III and IV (AJCC/UICC, V2, 2018), the survival time is less than 4 months, and there is currently no standard treatment. The Gemox chemotherapy (oxaliplatin + gemcitabine) has been used in the treatment of advanced BTC, but the efficacy is still unsatisfactory. Donafenib is a small molecule multi-kinase inhibitor, the main targets including VEGFR1-3, PDGFRα, RET(ret proto-oncogene ), c-KIT(KIT proto-oncogene, receptor tyrosine kinase), Raf,FLT3,have anti-angiogenic effects, have been proven effective in hepatocellular carcinoma. In recent years, monoclonal antibodies against programmed cell death protein 1 (PD1) have shown remarkable therapeutic effects in the treatment of various solid tumors. Prior to this, the combined treatment of GEMOX combined with Donafenib and Tislelizumab was proved satisfying safety. Meanwhile,the phase-I trial showed good efficacy in conversion rate and 6-month overall survival rate. Due to the limitted small sample size of the phase I trial, the investigators aim to expand the sample size to further verify the effects and safety of combined therapy in the study.

GEMOX Combined With Donafenib and Tislelizumab in Advanced Biliary Tract Carcinoma

Effects and Safety of GEMOX Combined With Donafenib and Tislelizumab in Advanced Biliary Tract Carcinoma：a Prospective, Single-arm, Single-center Phase II Study

objective response rate(ORR)，defined as percentage of participants achieving assessed complete response (CR) and partial response (PR) by the investigator according to the RECIST 1.1

Conversion rate, defined as the percentage of the conversion of patients with BTC assessed as unresectable into resectable through interventions, including the conversion of unresectable into resectable in the scientific sense such as insufficient future liver remnant(FLR), as well as the conversion of R1 and R2 to R0.

progression-free survival(PFS), defined as the time from enrollment to the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by investigator

overall survival(OS), defined as the time from enrollment to death due to any cause.

Incidence, severity, and relationship to study drugs of all adverse events (AEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs).

Fudan University

professor

Osteosarcoma

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 30 milligrams per meter square (mg/m\^2) orally twice weekly in treatment sequence ABCD (Treatment A: fasted, tablet formulation on Day 1 of Week 1; Treatment B: high-fat meal, tablet formulation on Day 1 of Week 2; Treatment C: low-fat meal, tablet formulation on Day 1 of Week 3; Treatment D: low-fat meal, capsule formulation on Day 1 of Week 4 in Cycle 1 (Weeks 1 to 4).

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m\^2 orally twice weekly in treatment sequence BADC (Treatment B: high-fat meal, tablet formulation on Day 1 of Week 1; Treatment A: fasted, tablet formulation on Day 1 of Week 2; Treatment D: low fat meal, capsule formulation on Day 1 of Week 3; Treatment C: low-fat meal, tablet formulation on Day 1 of Week 4 in Cycle 1 (Weeks 1 to 4).All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1.

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 50 mg/m\^2 first generation tablets twice weekly on Days 1 and 3 of each week within 30 minutes of solid food consumption.

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 60 mg/m\^2 orally in treatment sequence ABC (Treatment A: current \[1st generation\] tablets on Day 1 of Week 1; Treatment B: new \[2nd generation\] tablets on Day 1 of Week 2; Treatment C: suspension dose of current \[1st generation\] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1.

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 60 mg/m\^2 orally in treatment sequence CAB (Treatment C: suspension dose of current \[1st generation\] tablets on Day 1 of Week 1; Treatment A: current \[1st generation\] tablets on Day 1 of Week 2; Treatment B: new \[2nd generation\] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1.

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 60 mg/m\^2 orally in treatment sequence BCA (Treatment B: new \[2nd generation\] tablets on Day 1 of Week 1; Treatment C: suspension dose of current \[1st generation\] tablets on Day 1 of Week 2; Treatment A: current \[1st generation\] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1.

KCP-330

Michael Kauffman, MD, Ph.D

The purpose of this research study is to find out more information such as: to determine the effects of high and low fat foods on the pharmacokinetics (PK) of oral KPT-330 tablets and to compare PK of capsules and tablets in Arms 1 and 2; to evaluate tumor response in sarcoma participants in Arm 3; to compare the PK of 60 milligrams (mg) of the new, 2nd generation tablet formulation and 60 mg of the selinexor suspension formula to the current, 1st generation tablets.

A Phase I Trial to Assess the Effects of Food and Formulation on PK of KPT-330 in Patients With Sarcoma

An Open-Label Phase IB Trial To Evaluate the Effects of Food and Formulation on Pharmacokinetics of the Oral Selective Inhibitor of Nuclear Export/SINE Compound KPT-330 in Patients With Soft-Tissue or Bone Sarcoma

AUC0-t was defined as area under the concentration-time curve from time zero to the last non-zero concentration.

AUC0-inf was defined as area under the concentration-time curve from time zero to infinity (extrapolated), AUC0-inf was calculated as AUC0-t + Ct/ elimination rate constant (kel), where: Ct = the last observed non- zero concentration.

Cmax was defined as maximum observed concentration, taken directly from the plasma concentration data.

Tmax was defined as time of first observation of Cmax, taken directly from the plasma concentration data.

t1/2 was the terminal phase half-life, it was calculated as ln(2)/kel.

Apparent total body clearance was calculated as Dose/AUC0-inf, uncorrected for fraction absorbed; reported normalized by participant body weight (kilogram \[kg\]).

Vd/F was calculated as Dose/ (kel \*AUC0-inf), uncorrected for fraction absorbed; reported normalized by participant body weight (kg).

Best overall response rate was defined as the percentage of participants who achieved complete response (CR), and partial response (PR), as assessed by the RECIST v1.1 criteria. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non target) must have reduction in the short axis to less than (\<) 10 millimeter (mm). PR was defined as At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum longest diameter (LD).

Duration of at least stable disease was defined as the time from the date of first dose of study treatment to first documented radiologic evidence of disease recurrence or progression as per RECIST v1.1 Criteria. Participants without evidence of progression were censored at time of last disease assessment. Progressive Disease (PD) was defined as at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions also constituted progressive disease.

PFS was defined as the time from the date of randomization until the first date of Independent Review Committee (IRC)-confirmed PD per RECIST v1.1, or death due to any cause. PD was defined as at least a 20% increase in the sum of the longest diameter (SLD), taking as reference the smallest sum of the longest diameter (SLD) recorded from baseline or the appearance of 1 or more new lesions. Participants who were last known to be alive and without evidence of progression were censored at time of last disease assessment. If date of progression or death occurred after more than 1 missed disease assessment interval, or 30 days after end of treatment, participants were censored at the time of last evaluable disease assessment prior to the missed assessment.

OS was defined as the time from date first dose of study treatment to the date of death. Participants who were still alive prior to the data cutoff for final efficacy analysis, or who dropped out prior to study end, were censored at the day they were last known to be alive.

TTP was defined as the time from date of first dose of study treatment to first documented evidence of disease recurrence or progression, or death due to disease progression, whichever occurred first. Participants without evidence of progression were censored at time of last evaluable disease assessment.

GMI was defined as the ratio between the TTP with selinexor and the TTP with the most recent prior treatment. GMI was calculated, using a previously described threshold of 1.3 or greater as a sign of potential drug activity and improved overall survival.

An AE was any untoward medical occurrence in a participant administered a pharmaceutical product during the course of a study and which does not necessarily have to have a causal relationship with this treatment. SAE defined as any AE, occurring at any dose (including after the informed consent form was signed and prior to dosing) that and regardless of causality that: results in death, is life-threatening (participant was at immediate risk of death from event as it occurred), requires in-patient hospitalization (formal admission to a hospital for medical reasons) or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect. TEAE was defined as any AE with onset or worsening of a pre-existing condition on or after the first administration of study treatment through 30 days following last dose or any event considered drug-related by the investigator through the end of the study.

AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign, symptom, or medical condition that occur after participant's signed informed consent obtained. TEAE was defined as any AE with onset or worsening of a pre-existing condition on or after the first administration of study treatment through 28 days following last dose or any event considered drug-related by the investigator through the end of the study. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death.

Number of participants with clinically significant laboratory abnormalities including clinical chemistry, hematology, coagulation and urinalysis. Number of participants with clinically significant laboratory abnormalities which were deemed clinically significant by the investigator were reported.

Vital signs included blood pressure (systolic blood pressure and diastolic blood pressure). Measurements were made after the participant had been resting supine for a minimum of 5 minutes. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose based on the condition met (Yes/No). Number of participants with clinically significant changes in vital signs with condition (Yes) were only reported.

Twelve lead ECGs were obtained after the participant has rested in a supine position for at least 5 minutes. Clinically significant findings were defined as such in the opinion of the investigator or designated physician occurring at any time on treatment from normal pre-dose.

Karyopharm Therapeutics Inc

Safety population consisted of all participants who received at least one dose of selinexor. As pre-specified in SAP, safety data was collected and analyzed as per the individual arms with specified treatment sequences only.

Arm 1:

Arm 2:

Arm 3:

Arm 4:

Arm 5:

Arm 6:

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m\^2 orally twice weekly in treatment sequence ABCD (Treatment A: fasted, tablet formulation on Day 1 of Week 1; Treatment B: high-fat meal, tablet formulation on Day 1 of Week 2; Treatment C: low-fat meal, tablet formulation on Day 1 of Week 3; Treatment D: low-fat meal, capsule formulation on Day 1 of Week 4 in Cycle 1 (Weeks 1 to 4).

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m\^2 orally twice weekly in treatment sequence BADC (Treatment B: high-fat meal, tablet formulation on Day 1 of Week 1; Treatment A: fasted, tablet formulation on Day 1 of Week 2; Treatment D: low-fat meal, capsule formulation on Day 1 of Week 3; Treatment C: low-fat meal, tablet formulation on Day 1 of Week 4 in Cycle 1 (Weeks 1 to 4).

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 50 mg/m\^2 first generation tablets twice weekly on Days 1 and 3 of each week within 30 minutes of solid food consumption.

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 60 mg/m\^2 orally in treatment sequence ABC (Treatment A: current \[1st generation\] tablets on Day 1 of Week 1; Treatment B: new \[2nd generation\] tablets on Day 1 of Week 2; Treatment C: suspension dose of current \[1st generation\] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1.

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 60 mg/m\^2 orally in treatment sequence CAB (Treatment C: suspension dose of current \[1st generation\] tablets on Day 1 of Week 1; Treatment A: current \[1st generation\] tablets on Day 1 of Week 2; Treatment B: new \[2nd generation\] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1.

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 60 mg/m\^2 orally in treatment sequence BCA (Treatment B: new \[2nd generation\] tablets on Day 1 of Week 1; Treatment C: suspension dose of current \[1st generation\] tablets on Day 1 of Week 2; Treatment A: current \[1st generation\] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

American Indian or Alaska Native

Asian

Native Hawaiian or Other Pacific Islander

Black or African American

White

Unknown or Not Reported

Other

Race/Ethnicity, Customized

Safety population consisted of all participants who received at least one dose of selinexor.

Jatin Shah, MD

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (i.e. Treatment A: fasted, tablet formulation on Day 1 \[Week 1\] in Arm 1 and Day 1 \[Week 2\] in Arm 2).

Arms 1 and 2: Treatment A: Fasted, Tablet Formulation

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (i.e. Treatment B: high-fat meal, tablet formulation on Day 1 \[Week 2\] in Arm 1 and Day 1 \[Week 1\] in Arm 2).

Arms 1 and 2: Treatment B: High-Fat Meal, Tablet Formulation

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (i.e. Treatment C: low-fat meal, tablet formulation on Day 1 \[Week 3\] in Arm 1 and Day 1 \[Week 4\] in Arm 2).

Arms 1 and 2: Treatment C: Low-Fat Meal, Tablet Formulation

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (i.e. Treatment D: low-fat meal, capsule formulation on Day 1 \[Week 4\] in Arm 1 and Day 1 \[Week 3\] in Arm 2).

Arms 1 and 2: Treatment D: Low-Fat Meal, Capsule Formulation

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 60 mg/m\^2 orally in randomized treatment sequence (i.e. Treatment A: current \[1st generation\] tablets on Day 1 and 3 in Arm 4, 5 and 6 for Cycle 1 (Weeks 1 to 3).

Arms 4, 5, and 6: Treatment A: First Generation Tablet

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 60 mg/m\^2 orally in randomized treatment sequence (i.e. Treatment B: new \[2nd generation\] tablets on Day 1 in Arm 4, 5 and 6 for (Weeks 1 to 3).

Arms 4, 5, and 6: Treatment B: Second Generation Tablet

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 60 mg/m\^2 orally in randomized treatment sequence (i.e. Treatment C: suspension dose of current \[1st generation\] tablets on Day 1 and 3 in Arm 4, 5 and 6 for (Weeks 1 to 3).

Arms 4, 5, and 6: Treatment C: Oral Suspension

Pharmacokinetic (PK) population included all participants in Arms 1, 2 and Arms 4, 5, and 6 who received selinexor, and for whom the PK profile for all treatments could be adequately characterized. Here 'overall number of participants analyzed' signifies number of participants evaluable for this outcome measure. As pre-specified in SAP and protocol Arm 3 was a non-PK group assessment, so data was not collected and analyzed for this PK outcome.

Area Under the Concentration-time Curve From the Time Zero to the Last Non-zero Concentration (AUC0-t) of Selinexor

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (i.e. Treatment A: fasted, tablet formulation on Day 1 \[Week 1\] in Arm 1 and Day 1 \[Week 2\] in Arm 2).

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (i.e. Treatment B: high-fat meal, tablet formulation on Day 1 \[Week 2\] in Arm 1 and Day 1 \[Week 1\] in Arm 2).

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (i.e. Treatment C: low-fat meal, tablet formulation on Day 1 \[Week 3\] in Arm 1 and Day 1 \[Week 4\] in Arm 2).

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (i.e. Treatment D: low-fat meal, capsule formulation on Day 1 \[Week 4\] in Arm 1 and Day 1 \[Week 3\] in Arm 2).

PK population included all participants in Arms 1, 2 and Arms 4, 5, and 6 who received selinexor, and for whom the PK profile for all treatments could be adequately characterized. Here 'overall number of participants analyzed' signifies participants who are evaluable for this outcome measure. As pre-specified in SAP and protocol Arm 3 was a non-PK group assessment, so data was not collected and analyzed for this PK outcome.

Area Under the Concentration Time Curve From the Time Zero to Extrapolated to Infinity (AUC0-inf) of Selinexor

Maximum Observed Plasma Concentration (Cmax) of Selinexor

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (i.e. (i.e. Treatment A: fasted, tablet formulation on Day 1 \[Week 1\] in Arm 1 and Day 1 \[Week 2\] in Arm 2).

Time of First Maximum Observed Concentration (Tmax) of Selinexor

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 60 mg/m\^2 orally in randomized treatment sequence (i.e. Treatment A: current \[1st generation\] tablets on Day 1 and 3 \[Week 1 and 3\] in Arm 4 and 6 and Day 1 \[Week 2\] in Arm 2 for one cycle (Weeks 1 to 3).

Terminal Phase Half-Life (t1/2) of Selinexor

Apparent Total Body Clearance (CL/F) of Selinexor

Apparent Volume of Distribution (Vd/F) of Selinexor

Complete Response (CR)

Partial Response (PR)

Participants with liposarcoma received selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (A, B, C, D) in Arm 1 and 2 for one cycle (Weeks 1 to 4); 50 mg/m\^2 first generation tablets twice weekly on Days 1 and 3 in Arm 3; 60 mg/m\^2 orally in randomized treatment sequence (A, B, C) on Day 1 and 3 for 1st generation tablets and Day 1 for 2nd generation tablets for one cycle (Weeks 1 to 3).

Liposarcoma

Participants with leiomyosarcoma received selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (A, B, C, D) in Arm 1 and 2 for one cycle (Weeks 1 to 4); 50 mg/m\^2 first generation tablets twice weekly on Days 1 and 3 in Arm 3; 60 mg/m\^2 orally in randomized treatment sequence (A, B, C) on Day 1 and 3 for 1st generation tablets and Day 1 for 2nd generation tablets for one cycle (Weeks 1 to 3).

Leiomyosarcoma

Participants with Other sarcoma received selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (A, B, C, D) in Arm 1 and 2 for one cycle (Weeks 1 to 4); 50 mg/m\^2 first generation tablets twice weekly on Days 1 and 3 in Arm 3; 60 mg/m\^2 orally in randomized treatment sequence (A, B, C) on Day 1 and 3 for 1st generation tablets and Day 1 for 2nd generation tablets for one cycle (Weeks 1 to 3).

Other Sarcoma

Safety population consisted of all participants who received at least one dose of selinexor. Data for this outcome measure analysis was planned to be analyzed as per disease specific sarcoma.

Percentage of Participants With Best Overall Response According to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 Criteria

Safety population consisted of all participants who received at least one dose of selinexor. Data for this outcome measure was planned to be analyzed as per disease specific sarcoma.

Duration of Stable Disease as Per RECIST v1.1 Criteria

Progression Free Survival (PFS) as Per RECIST v1.1 Criteria

Overall Survival (OS)

Time to Progression (TTP)

GMI <= 1.33

GMI > 1.33

Safety population consisted of all participants who received at least one dose of selinexor. Data for this outcome measure was planned to be analyzed as per disease specific sarcoma. Here 'overall number of participants analyzed' signifies participants who were evaluable for this outcome measure.

Number of Participants With Growth Modulation Index (GMI) Less Than or Equal to (<=) 1.33 and Greater Than (>) 1.33

Participants with TEAEs

Participants with Serious TEAEs

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 milligrams per meter square (mg/m\^2) orally twice weekly in treatment sequence ABCD (Treatment A: fasted, tablet formulation on Day 1 of Week 1; Treatment B: high-fat meal, tablet formulation on Day 1 of Week 2; Treatment C: low-fat meal, tablet formulation on Day 1 of Week 3; Treatment D: low-fat meal, capsule formulation on Day 1 of Week 4 in Cycle 1 (Weeks 1 to 4).

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m\^2 orally twice weekly in treatment sequence BADC (Treatment B: high-fat meal, tablet formulation on Day 1 of Week 1; Treatment A: fasted, tablet formulation on Day 1 of Week 2; Treatment D: lowfat meal, capsule formulation on Day 1 of Week 3; Treatment C: low-fat meal, tablet formulation on Day 1 of Week 4 in Cycle 1 (Weeks 1 to 4).

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m\^2 orally twice weekly in treatment sequence BADC (Treatment B: high-fat meal, tablet formulation on Day 1 of Week 1; Treatment A: fasted, tablet formulation on Day 1 of Week 2; Treatment D: low fat meal, capsule formulation on Day 1 of Week 3; Treatment C: low-fat meal, tablet formulation on Day 1 of Week 4 in Cycle 1 (Weeks 1 to 4).

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity

Hematology

Clinical Chemistry

Coagulation: Prothrombin intl. normalized ratio

Urinalysis

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and other sarcoma) received selinexor 50 mg/m\^2 first generation tablets twice weekly on Days 1 and 3 of each week within 30 minutes of solid food consumption.

Number of Participants With Clinically Significant Laboratory Abnormalities

Systolic Blood Pressure: < 100 mmHg (Yes)

Systolic Blood Pressure: > 10 mmHg decrease from baseline (Yes)

Systolic Blood Pressure: > 20 mmHg decrease from baseline (Yes)

Systolic Blood Pressure: < 100 mmHg and > 10 mmHg decrease from baseline (Yes)

Systolic Blood Pressure: < 100 mmHg and > 20 mmHg decrease from baseline (Yes)

Diastolic Blood Pressure: < 60 mmHg (Yes)

Diastolic Blood Pressure: > 5 mmHg decrease from baseline (Yes)

Diastolic Blood Pressure: > 10 mmHg decrease from baseline (Yes)

Diastolic Blood Pressure: < 60 mmHg and > 5 mmHg decrease from baseline (Yes)

Diastolic Blood Pressure: < 60 mmHg and > 10 mmHg decrease from baseline (Yes)

Systolic Blood Pressure : > 140 mmHg (Yes)

Systolic Blood Pressure: > 160 mmHg (Yes)

Systolic Blood Pressure: > 10 mmHg increase from baseline (Yes)

Systolic Blood Pressure: > 20 mmHg increase from baseline (Yes)

Systolic Blood Pressure: > 160 mmHg and > 10 mmHg increase from baseline (Yes)

Systolic Blood Pressure: > 160 mmHg and > 20 mmHg increase from baseline (Yes)

Diastolic Blood Pressure: > 90 mmHg (Yes)

Diastolic Blood Pressure: > 100 mmHg (Yes)

Diastolic Blood Pressure: > 5 mmHg increase from baseline (Yes)

Diastolic Blood Pressure: > 10 mmHg increase from baseline (Yes)

Diastolic Blood Pressure: > 100 mmHg and > 5 mmHg increase from baseline (Yes)

Diastolic Blood Pressure: > 100 mmHg and > 10 mmHg increase from baseline (Yes)

Number of Participants With Clinically Significant Changes in Vital Signs

Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs)

Overall Study

Digestive System Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Central Nervous System Depressants

Anesthetics

Anesthetics, Local

The exercise regime consists of 10 sessions of exercise against a constant load, each lasting 60 seconds, separated by 60 seconds of recovery eliciting 90% maximal heart rate. The 6 sessions are held over a 2 week period.

Exercise programme

muscle biopsy under local anaesthetic taken from the thigh, again for analysis and storage 3 times: before, during and after the exercise programme

Muscle biopsy

Tamas Hickish, FRCP

This pilot study looks to explore the biological effects of exercise on cancer and muscle cells using a two week exercise program (HIThigh intensity training) on 20 patients with newly diagnosed and operable colorectal cancer following diagnosis and prior to surgery. Maximal oxygen uptake will also be measured. The aim of this pilot is to assess the feasibility of recruiting participants to and carrying out a two week preoperative exercise program in patients with colorectal cancer.

Patients undergoing investigation for symptoms of colorectal cancer presenting to the hospital will undergo standard diagnostic procedures. Once resectable nonmetastatic cancer has been diagnosed (i.e. cancer that has not spread beyond the bowel), is amenable to surgical resection as decided by the colorectal multidisciplinary and if the patient fulfills the selection criteria, they will be asked if they wish to participate in the study. They will be given information regarding the study at the time of diagnosis. If they give their consent then a formal consenting process will take place at the next routine appointment.

During this appointment the patient will have the opportunity to ask questions. A member of the study team will explain the study in detail, answer any questions potential participants (and their partners/ carers) have. The patient is free to refuse participation or withdraw from the study at any time without this affecting their care, this is explained in the information and will be discussed further at the time of informed consent. If the patient agrees to participate in the trial, following the provision of informed consent and before embarking on the exercise programme they will need to fill in two questionnaires, the International Physical Activity Questionnaire (Long) and Dietary Intervention in Primary Care Questionnaire (DINE). They will be counseled to try and maintain their normal exercise level and their calorie intake. Blood samples will also be taken, analyzed and stored for further analysis including possible genetic analysis at a later stage before starting the exercise regime. They will have a muscle biopsy under local anaesthetic taken from the thigh, again for analysis and storage.

Participants will undergo an initial assessment of their baseline exercise ability and oxygen absorption using an upright exercise bike with concurrent ECG readings and breath analysis. The two week preoperative exercise regime will be planned depending on the patient's operation date. The exercise regime consists of 10 sessions of exercise against a constant load, each lasting 60s, separated by 60s of recovery eliciting 90% maximal heart rate.

The 6 sessions are held over a 2 week period. Each patients exercise ability and oxygen absorption will be remeasured at the end of the 2 week period and a second sample of blood taken for comparison. During the operation a sample of adipose tissue near the tumour site will be taken separately to the main sample. A muscle biopsy from the thigh will also be taken at the same time. As a standard of clinical care all patients are reviewed in the outpatient setting 6 weeks postoperatively. When patients attend this follow up appointment a final blood test and muscle biopsy (under local anaesthetic) will be taken to assess the longer term effects of the exercise program. Patient consent will be sought for this separately although it will be discussed at the initial introduction to the study.

Patients are free to withdraw from the study at any time and if there are any adverse events or concerns regarding the continuation of the study for a patient then they will be withdrawn.

EDICT - Exercise inDuced Changes In Colorectal Cancer Tissues

Clinical and Biological Effects of a Preoperative Exercise Programme in Colorectal Tumour and Skeletal Muscle Tissues (Exercise inDuced Changes In Colorectal Cancer Tissues)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Late Effects of Treatment for Sarcomas in Children	NCT00006515	Sarcoma		7 Years -	National Institutes of Health Clinical Center (CC)
GEMOX Combined With Donafenib and Tislelizumab in Advanced Biliary Tract Carcinoma	NCT05668884	Biliary Tract C...	Combination of ...	18 Years - 75 Years	Fudan University
A Phase I Trial to Assess the Effects of Food and Formulation on PK of KPT-330 in Patients With Sarcoma	NCT01896505	Sarcoma	KCP-330	18 Years -	Karyopharm Therapeutics Inc
EDICT - Exercise inDuced Changes In Colorectal Cancer Tissues	NCT02056691	Colorectal Canc...	Exercise progra... Muscle biopsy	18 Years -	The Royal Bournemouth Hospital

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Spots Global Cancer Trial Database for effects

Every month we try and update this database with for effects cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for effects cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.