Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Rare Diseases

Recurrence

Osteosarcoma

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Sarcoma

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

For subjects age 18 and older, Regorafenib will be administered as 80mg oral once daily on Cycle 1, Days 1-7 and then escalated to 120 mg once daily for Cycle 1, Days 8-21 if no Grade 2 or above regorafenib adverse events occur. For subsequent cycles, the highest tolerated dose will be taken once daily on days 1-21 of each 28-day cycle.

Regorafenib 40 MG

For subjects younger than 18 years, Regorafenib will be administered as 60mg/m2/dose (rounded to the nearest 20mg, maximum dose of 80mg) once daily for Cycle 1, Days 8-21 if no Grade 2 or above regorafenib-related adverse events occur. For subsequent cycles, the highest tolerated dose will be taken once daily on days 1-21 of each 28-day cycle.

Regorafenib 20MG

For subjects age 18 and older, Nivolumab will be administered at 480mg IV over 30 min every 28 days.

For subjects younger than 18 years, Nivolumab 3mg/kg (maximum dose 240mg) will be administered IV over 30 minutes on day 1 and 15 of each 28-day cycle.

A phase 2 study of regorafenib in combination with nivolumab in patients with refractory or recurrent osteosarcoma.

This is a single arm, Simon two-stage historically controlled study to compare the 4 month progression-free survival rate of patients with relapsed/refractory osteosarcoma treated with regorafenib in combination with nivolumab to those who received regorafenib alone (historical control).

SARC038: Phase 2 Study of Regorafenib and Nivolumab in Osteosarcoma

SARC038: A Phase 2 Study of Regorafenib in Combination With Nivolumab in Patients With Refractory or Recurrent Osteosarcoma

To compare the 4-month progression-free survival (PFS) rate in patients with relapsed or refractory osteosarcoma administered regorafenib in combination with nivolumab to historical controls who received regorafenib alone, as per iRECIST. PFS will be determined as the time from the start of study treatment (Cycle 1, Day 1) to time of disease relapse, disease progression, or death from any cause, using iRECIST. The proportion of patients who do not experience one of these events at 4 months will be determined.

To estimate the objective response rate (ORR) in patients with relapsed or refractory osteosarcoma administered regorafenib in combination with nivolumab, according to iRECIST. Objective tumor response, defined as achievement of nadir response of complete response (CR) or partial response (PR) by iRECIST without prior progression any time during protocol therapy.

To estimate the PFS, including median PFS, in this population. Progression-free survival (PFS) defined as the time from study entry to disease relapse, disease progression, or death from any cause, using iRECIST. Patients without an event will be censored at the time of last disease follow-up.

To compare the 4-month PFS rate and ORR to historical controls in this population, according to RECIST 1.1. Duration of response is defined as the time from a nadir tumor response of CR/PR to disease progression.

To describe the toxicities of regorafenib in combination with nivolumab in patients with relapsed or refractory osteosarcoma. Adverse events will be graded as defined in CTCAE v. 5.0 during each therapy course.

To estimate 1-year and 2-year overall survival (OS) in patients with relapsed or refractory osteosarcoma treated with regorafenib in combination with nivolumab. Overall survival, defined as the time from study entry to death from any cause. Patients who are alive at the time of analysis will be censored at the date of last follow-up.

Sarcoma Alliance for Research through Collaboration

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Liver Neoplasms

Neoplasms, Glandular and Epithelial

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Hematinics

Amino Acids

Antibodies

Immunoglobulins

Liver Extracts

Endothelial Growth Factors

Mitogens

Tyrosine Kinase Inhibitors

Immunoglobulins, Intravenous

Sorafenib

Tyrosine

Arm A: Regorafenib Cycle 1:

* 80 mg daily Week 1
* 120 mg daily Week 2
* 160 mg daily week 3 then 1 week off followed by Cycle 2+ (160 mg for 21 days/1 week off) Subsequent Treatment Cycles
* 160 mg daily for 21 days, then 1 week off.

Arm B: Regorafenib Cycle 1:

* 160 mg daily for 21 days/then 1 week off Subsequent Treatment Cycles
* 160 mg daily for 21 days, then 1 week off

Regorafenib (BAY 73-4506) is an oral small molecule tyrosine kinase inhibitor (TKI) that potently blocks multiple protein kinases, including kinases involved in tumor angiogenesis (vascular endothelial growth factor receptor \[VEGFR\] 1, 2, 3, Tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 2 \[TIE2\]), stem cell growth factor receptor (KIT, rearranged during transfection \[RET\], p38-alpha, a member of the mitogen activated protein kinase \[MAPK\] family, proto-oncogene c-RAF \[c-RAF\], proto-oncogene BRAF \[BRAF\], BRAFV600E), metastasis (VEGFR3, platelet-derived growth factor receptor \[PDGFR\], fibroblast growth factor receptor1 \[FGFR1\]) and tumor immunity (colony stimulating factor 1 receptor \[CSF1R\]).

Catherine T Frenette, MD

Madappa Kundranda, MD

This is a randomized, two arm, phase II study of 1st Cycle dose optimization for regorafenib treatment compared to standard dose of regorafenib treatment in HCC patients for whom the physician is intending to treat with regorafenib and who failed any 1st line systemic treatment.

In this study, the investigators intend to evaluate the regorafenib ReDOS strategy to optimize the dose of regorafenib in patients with unresectable HCC (uHCC) who progressed during or after the first-line systemic treatment. This would allow improving the tolerability profile for patients such as those not selected based on prior sorafenib tolerability. The proposed regorafenib dosing escalation strategy for subjects randomized to the Arm A starting 80 mg/day dose for one week (Cycle 1, Week 1) is, if absent significant drug-related toxicities, to escalate to 120 mg/day for another week (Cycle 1, Week 2), and then, again if absent significant related toxicities, escalate to a total dose of 160 mg/day (Cycle 1, Week 3) followed by a week-long break (Cycle 1, Week 4).

Arm B, the comparative arm, will include a standard dose/schedule regorafenib of a 160 mg/day starting on Cycle 1, Day 1. The primary goal of this Arm is compare whether, or not, an 80 mg/day starting dose of regorafenib that escalates weekly by 40 mg until 160 mg/day is non-inferior to the FDA approved labeling 160 mg starting dose of regorafenib in terms of Overall Survival (OS) in HCC subjects. The investigators will also compare the proportions of patients in each arm who complete two cycles of treatment and who intend to continue to a third cycle if no tumor progression is noted on the 8-week disease scan. Other outcomes such as Quality of Life measures, and toxicity profile with a focus on regorafenib related toxicities such as hand-foot skin reaction will also be assessed.

Patients will be randomized 1:1 to either Arm A receiving the Cycle 1 Week-1 80 mg daily dose or Arm B the standard FDA labeling 160 mg daily starting dose, with subsequent dose adjustments as needed. Patients with unacceptable toxicities at the 80 mg dose may be considered for further dose reduction but will no longer be included in the overall survival analysis. After the conclusion of Cycle 2 (Week 8 of treatment), if toxicities have sufficiently resolved, re-escalation is allowed 40 mg at a time every four weeks to a maximum of 160 mg/day at the discretion of the treating investigator.

Patients will continue treatment until progression, unacceptable adverse events, or patient refusal. Treatment will then be discontinued, and the patient will go to event monitoring.

Additionally, a site-optional and subject-optional sub-study collecting blood serum samples at the Screening Visit for "hold and store" for future analysis of CD14, CD15, and CD16 cells as well as other potential biomarkers to be determined.

Arm A will initiate Cycle 1 treatment at 80mg daily of regorafenib escalating up to but not exceeding 160mg daily at 40mg per week increments.

Arm B will initiate Cycle 1 treatment at 160mg daily of regorafenib.

This trial will not be masked, subjects will know which arm they are randomly assigned to.

Optimization for Regorafenib in HCC

A Randomized Phase II Study of First Cycle Optimization for Regorafenib Treatment Compared to Standard Dose of Regorafenib in Patients With HCC Who Failed Any 1st Line Systemic Treatment and for Whom the Physician is Intending to Treat With Regorafenib

Only aggregated data will be available for review, analysis and reporting.

The primary objective is to evaluate whether, or not, an 80 mg/day starting dose of regorafenib that escalates weekly by 40 mg until 160 mg/day is non-inferior compared to the FDA approved labeling 160 mg starting dose of regorafenib in terms of Overall Survival in HCC subjects.

Proportion of patients who complete two cycles of treatment and who intend to initiate Cycle 3 if no progression is noted on the planned 8-week scan

Progression-free survival (PFS) per RECIST v1.1 with exploratory analysis of progression-free survival (PFS) per mRECIST where available

Evaluate the dosing schedule of regorafenib treatment, including: cumulative doses received during first and second cycles, duration of treatment (DOT) measured from Cycle 1 Day 1 to the 1 Month Follow-Up 30 days after the last dose of regorafenib, and summary of additional dose patterns or parameters such as the median daily dose for each treatment arm.

The EORTC QOL-C30 Quality of Life questionnaire contains 30 questions around physical, day-to-day functioning, and side effects experienced measured on a 4 point Likert scale with a response range of "1-not at all," "2-a little bit," "3-quite a bit," and "4-very much." The results between the Arms, particularly for Cycle 1, will be compared.

An optional sub-study, collect and hold blood samples from 100 subjects for analysis of mononuclear cells (CD14, 15 \& 16 cells) and other potential biomarkers at a to-be-determined time point after completion of the study.

The FACT-Hep Quality of Life questionnaire contains 46 questions around physical, social/family, emotional, day-to-day functioning, and side effects experienced measured on a 5 point Likert scale with a response range of "0-not at all," "1-a little bit," "3-somewhat," "4-quite a bit," and "5-very much." The results between the Arms, particularly for Cycle 1, will be compared..

Bayer

SC Liver Research Consortium, LLC

HCC participants who received the treatment of Regorafenib

participants who received the treatment of Regorafenib

Jian Lu, MD

This is a non-interventional observational study with the primary objective of assessing the efficacy of regorafenib in patients with immediate or advanced stage HCC.

1. Study Objectives Primary Objective: To assess the efficacy of regorafenib in patients with immediate or advanced stage HCC Secondary objective: To assess the safety of regorafenib in patients with immediate or advanced stage HCC
2. Study Design This is a multicenter, retrospective, real-world study that will collect data from patients treated with regorafenib at medical centers in China.
3. Data Collection 3.1 Screening Period

The study procedures to be performed at screening include:

1. . Determine eligible subjects according to the inclusion/exclusion criteria and document the results.
2. . Collect demographic characteristics (eg, age, sex, weight, BMI, and ECOG score);
3. . Collect past medical history;
4. . Collect primary tumor site;
5. . Collect information on prior treatments: all treatments received since diagnosis of advanced HCC, including each treatment regimen (including first-line therapy), start and end date, duration, best response;
6. . Collect information on liver function and ECOG score prior to the first dose of regorafenib;
7. . Collect results of laboratory tests performed prior to and after the first dose of regorafenib, including haematology, biochemistry and genetic testing (if any);
8. . Collect imaging data: the last imaging procedure performed prior to the first dose of regorafenib, such as CT, PET-CT, MRI, and whole-body bone scan (with at least 1 measurable lesion); and information related to metastases (such as metastases to lymph node, bone and/or lung).

3.2 Data Review Period of Regorafenib Treatment

The following information obtained during each cycle of regorafenib will be collected retrospectively:

1. . Liver function and ECOG score obtained prior to each dose (ie., the first day of each cycle) of regorafenib;
2. . Initial dose of regorafenib;
3. . Timing and method of dose adjustment, and adjusted doses;
4. . Final daily dose of regorafenib;
5. . Best response, time to best response, and number of treatment cycles;
6. . Imaging findings (including metastatic sites) related to response evaluation;
7. . Hematology laboratory tests (related to the underlying disease, tumor progression, and ADR);
8. . Any adverse reaction and corresponding CTCAE grade;
9. . Interrupted or discontinued treatment;
10. . The most recent laboratory tests (or alternative doctor's advice and tests) performed prior to the first day of each treatment cycle, including but not limit to hematology and biochemistry.

3.3 Progression and Survival Data Collection Period

The following information obtained during each cycle of regorafenib will be collected retrospectively:

1. . Time to progression
2. . Pattern of progression
3. . Subsequent treatment regimen, dose, number of cycles, efficacy;
4. . Survival status, time of death or last follow-up.

4. Study Drug Generic name: Regorafenib Tablets Trade name: Stivarga® English name: Regorafenib Tablets

Dosage strength: 40 mg tablet Dosage form: Tablets Description: Oval tablets with pale-pink film coat Label dose and mode of administration: Recommended dosage is 160 mg, once daily for the first 21 days of each 28-day cycle. A minimum dose of 80 mg/day and a maximum dose of 160 mg/day are recommended.

A Real World Study of Regogfinib in HCC

A Real World Study of Regogfinib in the Treatment of Advanced Hepatocellular Carcinoma

Overall survival was defined as the time from the start of regorafenib treatment to the date of death from any cause or last follow-up

Progression-free survival was defined as the time from the start of regorafenib treatment to the date of the first documentation of disease progression or death from any cause.

Time to progression was defined as the time from the start of regorafenib treatment to the date of the first documentation of disease progression.

Objective response rate was defined as the proportion of patients with CR or PR in the overall population

Disease control rate was defined as the proportion of patients with CR or PR or stable disease (SD) in the overall population

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
SARC038: Phase 2 Study of Regorafenib and Nivolumab in Osteosarcoma	NCT04803877	Osteosarcoma Osteosarcoma in... Osteosarcoma Re... Osteosarcoma Me...	Regorafenib 40 ... Regorafenib 20M... Nivolumab	5 Years -	Sarcoma Alliance for Research through Collaboration
Optimization for Regorafenib in HCC	NCT04476329	Hepatocellular ...	Regorafenib 40 ...	18 Years -	SC Liver Research Consortium, LLC
Optimization for Regorafenib in HCC	NCT04476329	Hepatocellular ...	Regorafenib 40 ...	18 Years -	SC Liver Research Consortium, LLC
Optimization for Regorafenib in HCC	NCT04476329	Hepatocellular ...	Regorafenib 40 ...	18 Years -	SC Liver Research Consortium, LLC
A Real World Study of Regogfinib in HCC	NCT05557656	Hepatocellular ...	Regorafenib 40 ...	18 Years - 90 Years	Zhongda Hospital

Spots Global Cancer Trial Database for regorafenib 40 mg