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

Disease Attributes

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Unresectable disease (can not be surgically removed) will be enrolled into Cohort 1 and Resectable disease (can be surgically removed) which is limited only to the lung parenchyma will be enrolled into Cohort 2.

* Olaparib at a predetermined dose orally 2 times a day on days 1-28
* Ceralasertib will be given at a predetermined dose orally 2 times a day on days 1-14 in 28-day study cycles.

Patients can remain on treatment for up to 2 years if disease progression has not occurred.

Olaparib is taken by mouth, twice daily through out the 28 day study cycle.

Ceralasertib is taken by mouth, twice daily on days 1-14 of the study cycle.

Ceralasertib

Katherine Janeway, MD

Karina Wong

Rachel Mustain

Kieuhoa Vo, MD, MAS

Julia Glade Bender, MD

Andrew Livingston, MD

Jonathan Gill, MD

This study is being done in order to evaluate the effectiveness of using two drugs (olaparib and ceralasertib) to treat patients with osteosarcoma that has not responded to treatment or has come back after treatment

The names of the study drugs involved in this study are:

* Olaparib
* Ceralasertib

This is a single arm, phase 2, open-label clinical trial to evaluate the use of olaparib in combination with ceralasertib in 2 cohorts of patients aged 12-40 with recurrent osteosarcoma.

The research study procedures include screening for eligibility, study treatment, evaluations and follow-up visits.

* Cohort 1: Participants with unresectable osteosarcoma (unable to remove with surgery)
* Cohort 2: Participants with lung only resectable osteosarcoma (able to remove with surgery)

Participants will be given a drug diary to document information about the study treatment and study calender with information about what to expect during and between study visits. The names of the study drugs involved in this study are:

* Olaparib
* Ceralasertib

Each treatment cycle lasts 28 days and participants will receive study treatment up to 24 cycles (2 years).

It is expected that about 63 people will take part in this research study.

* The study is looking to test: whether olaparib and ceralasertib given together are effective in patients with recurrent or refractory osteosarcoma.
* how safe and how well tolerated olaparib and ceralasertib are when given together in patients with recurrent or refractory osteosarcoma.
* markers in the blood and in tumor tissue to see if there are certain features of the tumor that may indicate this combination of drugs is effective or not effective.

The U.S. Food and Drug Administration (FDA) has not approved Ceralasertib as a treatment for any disease.

This is the first time that Ceralasertib will be given to children.

The U.S. Food and Drug Administration (FDA) has not approved olaparib for recurrent osteosarcoma but it has been approved for other uses.

Olaparib With Ceralasertib in Recurrent Osteosarcoma

Phase II Trial of Olaparib in Combination With Ceralasertib in Patients With Recurrent Osteosarcoma

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Simon's two-stage design will be applied to the primary (binary) endpoint, event-free at 4-months. An event is defined as the occurrence of relapse, disease progression as defined by RECIST 1.1, or death from any cause.

Estimate the proportion of patients who have paired pre-/post-treatment tumor samples adequate for biomarker studies and / or derivation of PDX models.

Radiographic response according to RECIST criteria. confidence interval on the proportion.

An event is defined as progression, relapse, or death from any cause

Within Cohort 2, calculate the proportion who are event-free at 12- months, as the total number event-free at 12-months divided by the number of evaluable patients.

The number and proportion of adverse events, graded as defined by CTCAE version 5.0 will be tabulated by type and grade. This analysis will be performed overall and separately for Cohort 1 and 2. Within a given patient, a given adverse event will be counted only once at the highest grade.

Osteosarcoma Institute

AstraZeneca

Dana-Farber Cancer Institute

Principal Investigator

Ifosfamide

Isophosphamide mustard

Observational study

Celeste Cagnazzo, PhD

A multicentre, observational, retrospective study to analyse the efficacy of high dose isofosfamide thorugh elastomer in patients with relapsed/ refractory osteosarcoma

An Analysis of the Efficacy of High Dose Isofosfamide Through Elastomer

A Multicentre, Retrospective, Observational Study to Analyse the Efficacy of High Dose Isofosfamide Administered Through Elastomer in Patients With Relapsed/ Refractory Osteosarcoma

ratio of time to progression (TTP) with nth line of therapy (TTPn) to the most recent prior line of therapy (TTPn-1)

Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna

Azacitidine

Antimetabolites

Participants will receive 1 cycle of neoadjuvant Nivolumab or Nivolumab + Azacitidine, followed by surgery to render them in surgical remission. Subsequently they will continue to receive Nivolumab or Nivolumab + Azacitidine for 12 additional cycles or until recurrence, whichever occurs first. Once the recommended Phase II dose (RP2D) is identified during Phase I, the Dose Expansion Phase II will be opened at this dose level. The Phase II portion of the study will consist of a maximum 33 evaluable patients (27-30 in addition to the 3-6 enrolled at RP2D on the Phase I portion).

Participants will be treated with Nivolumab intravenously (IV), 3 mg/kg on days 1 and 15 of each cycle.

Phase I Dose Escalation - Dose level 1: NA. Dose level 2: 60 mg/m\^2. Dose level 3: 75 mg/m\^2. Phase II Expansion - Treated at recommended Phase II dose (RP2D).

Resection surgery at end of Cycle 1 treatment, day 28-35.

Post Treatment Surgery

Patrick A. Thompson, MD

Mihaela M Druta, MD

The purpose of this study is to evaluate the safety and efficacy of nivolumab, or nivolumab in combination with azacitidine in participants with recurrent, resectable osteosarcoma

Treatment will be administered in 28 day cycles with the first cycle in the neoadjuvant setting. This will be followed by surgery to render the participant in surgical remission. Subsequently the participant will continue to receive treatment for up to 12 additional cycles or until recurrence, whichever occurs first. For participants with known bilateral lung recurrence, the nodule\[s\] in one lung should be resected, prior to the first cycle of chemotherapy.

Phase Ib lead-in with extension to Phase II

Nivolumab or Nivolumab and Azacitidine in Patients With Recurrent, Resectable Osteosarcoma

A Phase Ib/II Study to Evaluate the Safety, Feasibility and Efficacy of Nivolumab or Nivolumab in Combination With Azacitidine in Patients With Recurrent, Resectable Osteosarcoma

If one or fewer dose limiting toxicities (DLT's) occur in 6 participants the study will advance to the next dose level. If 2 or more DLT's occur at a dose level, the prior dose level will be identified as the RP2D.

Continued complete remission by computed tomography (CT) scan 1 year after surgery.

EFS: The time from diagnostic biopsy until the earliest of: death, local recurrence, new metastatic disease, progression of metastatic disease or secondary malignancy, or date of last contact.

The percentage of participants alive at 1 year post surgery.

Bristol-Myers Squibb

H. Lee Moffitt Cancer Center and Research Institute

Gemcitabine

Docetaxel

observation

Franca Fagioli, MD

A retrospective observational study of the effectiveness of gemcitabine - docetaxel in patients with relapsed osteosarcoma who have been treated with HD IFO in first line treatment

Study of Effectiveness of GEMDOX in Relapsed Osteosarcoma

A Retrospective Observational Study of the Effectiveness of Gemcitabine -Docetaxel in Patients With Relapsed Osteosarcoma Who Have Been Treated With HD-IFO in First Line Treatment

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
Olaparib With Ceralasertib in Recurrent Osteosarcoma	NCT04417062	Osteosarcoma Osteosarcoma Re...	Olaparib Ceralasertib	12 Years - 40 Years	Dana-Farber Cancer Institute
An Analysis of the Efficacy of High Dose Isofosfamide Through Elastomer	NCT04651569	Osteosarcoma Re...	Observational s...	- 40 Years	Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna
Nivolumab or Nivolumab and Azacitidine in Patients With Recurrent, Resectable Osteosarcoma	NCT03628209	Osteosarcoma Osteosarcoma in... Osteosarcoma Re... Sarcoma	Nivolumab Azacitidine Post Treatment ...	- 39 Years	H. Lee Moffitt Cancer Center and Research Institute
Study of Effectiveness of GEMDOX in Relapsed Osteosarcoma	NCT04651179	Osteosarcoma Re... Osteosarcoma Me...	observation	4 Years -	Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna
Study of Effectiveness of GEMDOX in Relapsed Osteosarcoma	NCT04651179	Osteosarcoma Re... Osteosarcoma Me...	observation	4 Years -	Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna

Spots Global Cancer Trial Database for osteosarcoma recurrent