Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Sarcoma

Chondrosarcoma

Sarcoma, Alveolar Soft Part

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Alveolar Soft Part Sarcoma

Gastrointestinal Agents

All Drugs and Chemicals

Antiemetics

Antirheumatic Agents

Loperamide

Allopurinol

Antidiarrheals

Antimetabolites

Enzyme Inhibitors

Antioxidants

Protective Agents

Patients with sarcoma subtype: histologically or cytologically confirmed diagnosis of chondrosarcoma.

Supportive Care Guidelines for perifosine include antiemetic prophylaxis (antiemetics will be administered at the treating investigator's discretion), diarrhea management (loperamide), and hyperuricemia prophylaxis (allopurinol).

Patients with sarcoma subtype: histologically or cytologically confirmed diagnosis of alveolar soft part sarcoma.

Supportive Care Guidelines for perifosine include antiemetic prophylaxis (antiemetics will be administered at the treating investigator's discretion), diarrhea management (loperamide), and hyperuricemia prophylaxis (allopurinol).

Patients with sarcoma subtype: histologically or cytologically confirmed diagnosis of extra-skeletal myxoid chondrosarcoma.

Supportive Care Guidelines for perifosine include antiemetic prophylaxis (antiemetics will be administered at the treating investigator's discretion), diarrhea management (loperamide), and hyperuricemia prophylaxis (allopurinol).

Perifosine is available in 50 mg tablets. Patients will take two perifosine 50 mg tablets orally once a day at bedtime with food.

Perifosine

All patients should be instructed to take loperamide at the earliest signs of diarrhea and/or abdominal cramping after beginning perifosine.

Patients with a known history of hyperuricemia and/or gout should receive prophylactic treatment with allopurinol 300 mg po daily.

Antiemetic prophylaxis will be administered at the treating investigator's discretion.

Dejka Araujo, MD

This is a phase II study of perifosine in patients with chondrosarcomas, alveolar soft part sarcomas and extra-skeletal myxoid chondrosarcomas. Patients will receive perifosine 100 mg orally qhs with food until disease progression. The goals of this study include:

* In this study a daily dose of perifosine previously determined to be relatively non-toxic will be evaluated in patients with chondrosarcomas, alveolar soft part sarcomas and extra-skeletal myxoid chondrosarcomas.
* Response to therapy will be based on regression of measurable disease according to Choi criteria. Time to progression and duration of stable disease will be measured as secondary endpoints of the study.

This is a phase II study of perifosine in patients with chondrosarcomas, alveolar soft part sarcomas and extra-skeletal myxoid chondrosarcomas. Patients will receive perifosine 100 mg orally qhs with food until disease progression.

Perifosine is available in 50 mg tablets. Patients will take two perifosine 50 mg tablets orally once a day at bedtime with food. Administering the drug qhs has been shown to decrease gastrointestinal toxicity in some patients. Patients may need anti-emetics and/or anti-diarrheals. All patients may continue therapy unless disease progression is documented on two occasions at least 4 weeks apart. Patients who experience toxicity may continue on treatment with doses delayed or reduced. Evaluation of all lesions for progression or response will be made at 3-month intervals.

STUDY KEY POINTS

* Treatment will be administered on an outpatient basis in 28-day cycles.
* Growth factors should not be needed, however, use by patients on this trial is NOT prohibited.
* A favorable outcome will be defined as a complete or partial response according to the Choi criteria or stable disease by the Choi criteria for 6 months or longer.

One treatment arm: Perifosine. Three groups related to sarcoma subtype: histologically or cytologically confirmed diagnosis of (a) chondrosarcoma, (b) alveolar soft part sarcoma and (c) extra-skeletal myxoid chondrosarcoma.

A Trial of Perifosine in Patients With Chemo-Insensitive Sarcomas

Sarcoma Alliance for Research Through Collaboration (SARC) Multicenter Trial: A Phase II Trial of Perifosine in Patients With Chemo-Insensitive Sarcomas

To investigate whether perifosine has a response rate of \> 20% in this group of patients with chemo-insensitive sarcomas.

Best response recorded from the start of the treatment until disease progression/recurrence.

Stable disease is measured from the start of treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started.

Sarcoma Alliance for Research through Collaboration

AEterna Zentaris

Chordoma

Neoplasms, Germ Cell and Embryonal

Proton radiation total dose 72.00 to 79.2 Gy(RBE) in 40-44 fractions

Proton Therapy

The objectives of this study are 1) To evaluate the feasibility and acute side effects of proton therapy for chordomas and chondrosarcomas and 2) To evaluate clinical outcomes and long term side effects of proton beam radiation for treatment of chordomas and chondrosarcomas.

This trial will be conducted in two phases: a feasibility then a phase II trial. Once feasibility and safety are established in the first 12 pts. the phase II study will begin. Proton therapy at standard doses is not known to improve clinical outcome but will likely reduce fatigue and toxicity.

Proton Radiation for Chordomas and Chondrosarcomas

Proton Radiation For Chordomas and Chondrosarcomas

Any grade 3 or higher toxicity observed within 90 days from start of therapy.

Any grade 3 or higher toxicty observed later than 90 days from completion of therapy.

Abramson Cancer Center at Penn Medicine

Ronny L Rotondo, MD

The purpose of this study is to collect information from medical records to see what effects proton beam radiation has on cancer and analyze possible side effects.

Data collection will be obtained from the patient's medical records including initial evaluation, pathology report, dosimetry information, radiotherapy completion records and follow-up.

Proton Therapy for Chordomas and/or Chondrosarcomas

A Clinical Outcomes Protocol of Proton Beam Radiation Therapy for Chordomas and/or Chondrosarcomas of the Base of Skull and/or Spine

Specifically analyzing pituitary, visual and hearing function.

University of Florida

Osteosarcoma

Sarcoma, Ewing

Chondroma

Neoplasms, Bone Tissue

Ewing Sarcoma

For adult patients (≥18 years old) : 160 mg/d once daily for the 3 weeks on / 1 week off plus Best Supportive Care (BSC) until progression (according to RECIST 1.1), intolerance or withdrawal of consent .

For children Age ≥10 years to \<18 years old and BSA ≥1.30 m², regorafenib (82 mg/m²) once daily for the 3 weeks on/1 week off (without exceeding 160 mg/day) plus Best Supportive care (BSC) until progression (according to RECIST 1.1), intolerance or withdrawal of consent.

Placebo plus BCS until progression (according to RECIST V1.1) intolerance or withdrawal of consent. Patients who have received placebo will receive open-label regorafenib after objective tumor progression.

For adults patients and children with BSA ≥1.70 m² : 4 tablets once daily until progression or unacceptable toxicity For children with BSA ≥1.30 and ≤1.69 m² : 3 tablets once daily until progression or unacceptable toxicity

Regorafenib

For adults patients and children with BSA ≥1.70 m² : 4 tablets once daily and switch to regorafenib after confirmed progression For children with BSA ≥1.30 and ≤1.69 m² : 3 tablets once daily and switch to regorafenib after confirmed progression

Placebo

Sabrina YARA

Elsa KALBACHER, MD

Antoine ITALIANO, MD

Corinne DELCAMBRE, MD

Alice HERVIEU, MD

Nicolas PENEL, MD

Jean Yves BLAY, MD PhD

François BERTUCCI, MD PhD

Florence DUFFAUD, MD PhD

Didier CUPISSOL, MD

Antoine THYSS, MD PhD

Pascaline BOUDOU-ROUQUETTE, MD

Sophie PIPERNO-NEUMANN, MD

Christophe PERRIN, MD

Emmanuelle BOMPAS, MD

Olivier COLLARS, MD

Christine CHEVREAU, MD

Helene VEGAS, MD

Maria RIOS, MD

Olivier MIR, MD

INDICATION:

Metastatic bone sarcomas: conventional high grade osteosarcoma, Ewing sarcoma of bone, intermediate or high-grade chondrosarcomas and chordomas and either bone or soft tissue metastatic CIC-rearranged sarcomas

METHODOLOGY:

Randomized, placebo-controlled, multicentric, phase II study -This is a double-blind placebo-controlled trial, with 5 cohorts: cohort A: Osteosarcoma, cohort B: Ewing sarcoma, cohort C: Chondrosarcoma, cohort D : chondroma, cohort E: CIC-rearranged sarcoma. Cohort A, B and C will involve a total of 36 patients (24 Regorafenib + 12 placebo), cohort D a total of 24 evaluable patients (16 Regorafenib + 8 placebo) and cohort E will involve a total of 27 evaluable patients (18 Regorafenib + 9 placebo).

159 patients who meet the eligibility criteria will be randomly assigned in a 2:1 ratio to the following treatment groups :

The Arm A:

Regorafenib (160 mg/d) once daily for the 3 weeks on / 1 week off plus Best Supportive Care (BSC) until progression (according to RECIST 1.1), intolerance or withdrawal of consent .

Patients receiving regorafenib who experience disease progression and for whom in the investigator opinion, treatment with regorafenib is providing clinical benefit, may continue the treatment following consultation with the study coordinator and the sponsor.

The Arm B:

Placebo plus BSC until progression (according to RECIST V1.1) intolerance or withdrawal of consent. Patients who have received placebo will receive open-label regorafenib after objective tumor progression.

Patients will be stratified at randomization according to histology .

A Phase II Study Evaluating Efficacy and Safety of Regorafenib in Patients With Metastatic Bone Sarcomas

A Randomized Phase II, Placebo-controlled, Multicenter Study Evaluating Efficacy and Safety of Regorafenib in Patients With Metastatic Bone Sarcomas

Proportion of patients without disease progression at the defined timepoint after central radiological review (using RECIST 1.1)

from the date of randomization until the date of radiological progression or death whatever the cause (if death occurs before progression)

complete response (CR) or partial response (PR) according to RECIST 2009, version 1.1, for all cohorts, and CHOI criteria for chordoma

from the date of randomization until the date of death due to any cause

objective response of CR or PR, whichever is noted earlier, to first disease progression or death before progression

the proportion of patients without progression at 3 and 6 months post randomization

from date of randomization until the date of first observation of progression

ratio of time to PD under regorafenib to TTP under previous treatment

according to NCI-CTCAE V4-0 (National Cancer Institut Common Terminology Criteria for Adverse Events)

Progression Free Survival according to Choi criteria for Chordoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Trial of Perifosine in Patients With Chemo-Insensitive Sarcomas	NCT00401388	Chondrosarcomas Alveolar Soft P... Extra Skeletal ...	Perifosine Loperamide Allopurinol Antiemetics	13 Years -	AEterna Zentaris
Proton Radiation for Chordomas and Chondrosarcomas	NCT01449149	Chordomas Chondrosarcomas	Proton Therapy	18 Years -	Abramson Cancer Center at Penn Medicine
Proton Therapy for Chordomas and/or Chondrosarcomas	NCT00797602	Chordomas Chondrosarcomas		18 Years -	University of Florida
A Phase II Study Evaluating Efficacy and Safety of Regorafenib in Patients With Metastatic Bone Sarcomas	NCT02389244	Ewing Sarcomas Chondrosarcomas Osteosarcomas Chondroma CIC-Rearranged ...	Regorafenib Placebo	10 Years -	UNICANCER
Proton Radiation for Chordomas and Chondrosarcomas	NCT01449149	Chordomas Chondrosarcomas	Proton Therapy	18 Years -	Abramson Cancer Center at Penn Medicine
A Phase II Study Evaluating Efficacy and Safety of Regorafenib in Patients With Metastatic Bone Sarcomas	NCT02389244	Ewing Sarcomas Chondrosarcomas Osteosarcomas Chondroma CIC-Rearranged ...	Regorafenib Placebo	10 Years -	UNICANCER

Spots Global Cancer Trial Database for chondrosarcomas