Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Osteosarcoma

Sarcoma

Sarcoma, Ewing

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Ewing Sarcoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Topotecan

Lenograstim

Mitogens

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Topoisomerase I Inhibitors

Enzyme Inhibitors

Participants will be accrued to dose levels in cohorts of 3 using the 3 + 3 design with a combination of cabozantinib, topotecan and cyclophosphamide.

* Each study treatment cycle lasts 21 days.
* Participants may receive up to 17 cycles.
* Participants will be assigned a specific dose and schedule of the study drugs determined when enrolled in the study.

PO (dose and schedule based upon dose level and nomogram)

Cabozantinib

IV, over 30 minutes (schedule based upon dose level)

subcutaneous filgrastim (daily until ANC ≥ 1,500/mm3 after nadir) or pegfilgrastim (once) must be given, with choice of agent per institutional standard or treating physician preference, starting on day 5, 6, 7 or 8 (depending upon chemotherapy timing)

Myeloid growth factor

Steven C DuBois, MD

This research study is a clinical trial of a new combination of drugs as a possible treatment for relapsed/refractory Ewing sarcoma and/or osteosarcoma.

* The names of the drugs are:

  * Cabozantinib
  * Topotecan
  * Cyclophosphamide
* The names of the non-investigational supportive care drugs are:

  * Filgrastim, pegfilgrastim, or a related growth factor.

This is a prospective, open-label, single arm, phase 1 clinical trial. A single cohort of patients with relapsed or refractory Ewing sarcoma or osteosarcoma will be enrolled and treated in a 3+3 design with a combination of cabozantinib, topotecan and cyclophosphamide.

The research study procedures include screening for eligibility and study treatment including medical tests and follow up visits.

* The names of the drugs are:

  * Cabozantinib
  * Topotecan
  * Cyclophosphamide
* The names of the non-investigational supportive care drugs are:

  * Filgrastim, pegfilgrastim, or a related growth factor.

It is expected that up to 16 people will take part in this research study.

This research study is a Phase I clinical trial, which tests the safety of an investigational drug combination and also tries to define the appropriate doses of the drugs to use for further studies. "Investigational" means that the drug combination is being studied.

The FDA (the U.S. Food and Drug Administration) has approved all medications included in this trial as a treatment for multiple types of cancers.

The combination of topotecan and cyclophosphamide has been used for treatment of this population. Cabozantinib has been used alone for treatment of Ewing sarcoma and osteosarcoma and shown to have an effect in some patients. This is the first time that cabozantinib will be studied in combination with topotecan and cyclophosphamide.

Cabozantinib With Topotecan-Cyclophosphamide

Phase 1 Study of Cabozantinib in Combination With Topotecan-Cyclophosphamide for Patients With Relapsed Ewing Sarcoma or 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 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.

Combination of cabozantinib with cyclophosphamide and topotecan

* If no Dose Limiting Toxicities occur during the first cycle for all three subjects, dose escalation to the next highest dose level will occur for the next three enrolling patients.
* If one out of three patients experience a DLT during the first cycle of therapy, up to three additional subjects will then be enrolled at the same dose level for a total of six patients at this dose level. If two or more patients experience DLTs in the 1st cycle, the trial will stop enrollment and this dose level will be the MAD.
* Up to six additional patients will be enrolled at the dose level below the MAD, with the MTD being established once ≤1 patient in a dose level experiences DLTs.
* If two out of three patients experience DLTs during the 1st cycle, the protocol will halt enrollment at this dose level, which will be considered the MAD.

The CTCAE version 5.0 of the National Cancer Institute (NCI) for toxicity and performance reporting. Tabulations will be generated by toxicity type and grade, counting only the maximum grade per type within a given patient. Serious adverse events will be separately tabulated. This analysis will be conducted within the safety population.

The objective response rate to cabozantinib, topotecan and cyclophosphamide will be calculated as follows: (# responders) / (# of patients in the response analysis population) \* 100%. A 95% exact two-sided confidence interval will be placed on this proportion. In addition, the number and proportion of patients by level of response will be presented. Patients with an overall best objective response of partial response or complete response prior to local measures will be categorized as responders, and all other patients as non-responders. This analysis will be conducted within the response analysis population.

PFS will be estimated using Kaplan-Meier methods as time from study entry to first episode of disease progression or death, with patients without these events censored at last follow-up.

Dana-Farber Cancer Institute

Principal Investigator

Pediatric participants ≥ 2 to \< 18 years of age with previously treated solid tumors of any histology at 5 dose levels to determine the RP2D, followed by a safety expansion cohort.

Participants aged ≥ 6 to \< 18 years will be enrolled at the starting dose of 3.2 mg/m\^2 lurbinectedin. After the drug is deemed safe based safety and PK data from the older participants, participants aged ≥ 2 to \< 6 years are enrolled at the same starting dose. After this, the study opens to all participants (aged ≥ 2 to \< 18 years) for all dose levels.

Upon completion of the cohort at all dose levels, participants may be eligible to enroll in a safety expansion cohort.

Participants aged ≥ 2 to ≤ 30 years with recurrent/refractory Ewing sarcoma at the RP2D to assess safety and efficacy signals.

If a signal of efficacy is observed in Phase 1 Part 2, additional participants aged ≥ 2 to ≤ 30 years with recurrent/refractory Ewing sarcoma will be enrolled. Phase 2 will further assess the safety and efficacy of lurbinectedin monotherapy.

Administered as intravenous (IV) infusion once every 3 weeks (Q3W)

Lurbinectedin

Clinical Trial Disclosure & Transparency

Jazz Study Director

This study is conducted in two phases. The phase 1 portion of the study evaluates the safety, tolerability, pharmacokinetics (PK), recommended phase 2 dose (RP2D), and effectiveness of lurbinectedin monotherapy in pediatric participants with previously treated solid tumors. This is followed by the phase 2 portion, to further assess the effectiveness and safety in pediatric and young adult participants with recurrent/refractory Ewing sarcoma.

Study of Lurbinectedin Monotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Ewing Sarcoma

A Phase 1/2, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Recommended Phase 2 Dose (RP2D), and Efficacy of Lurbinectedin Monotherapy in Pediatric Participants With Previously Treated Solid Tumors Followed by Expansion to Assess Efficacy and Safety in Pediatric and Young Adult Participants With Relapsed/Refractory Ewing Sarcoma.

TEAEs are defined as adverse events (AEs) with an onset date on or after the date of the first dose of study treatment. An AE is a TEAE if it occurs up to 30 days after the last dose of study intervention.

Jazz Pharmaceuticals

Breast Neoplasms

Melanoma

Neuroblastoma

Rhabdomyosarcoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroectodermal Tumors, Primitive, Peripheral

Neoplasms, Neuroepithelial

Neoplasms, Glandular and Epithelial

Myosarcoma

Breast Diseases

Intraocular Melanoma

Phyllodes Tumor of the Breast

Gaucher Disease Type 2

Neuroendocrine Tumor

Neuroepithelioma

Immunomodulating Agents

Patients will be treated at 2 dose levels without lymphodepletion chemotherapy. Three patients will be evaluated and if safety is confirmed patients will be treated at the next dose level with C7R.GD2.CART cell infusion without lymphodepletion chemotherapy.

The protocol is divided into two arms, a high-risk group of patients with lung metastases (Arm B) and a standard risk group of all other patients (Arm A). The standard risk Arm A includes osteosarcoma patients without pulmonary disease. Each arm will undergo separate dose escalation.

Active dose levels:

C7R-GD2.CART cell without lymphodepletion (Arm A or Arm B)

Dose Level 2b = 3 x 10\^7 on day 0 and day 7

Dose Level 3b = 1 x 10\^8 on day 0 and day 7.

Day 7 dose (+- 2 days) will be omitted if patients have persistent CRS (Grade 2 or higher) experienced a DLT or for other clinical concerns at the discretion of the PI.

C7R-GD2.CART cells

Bilal Omer, MD

This study is for patients with neuroblastoma, sarcoma, uveal melanoma, breast cancer, or another cancer that expresses a substance on the cancer cells called GD2. The cancer has either come back after treatment or did not respond to treatment. Because there is no standard treatment at this time, patients are asked to volunteer in a gene transfer research study using special immune cells called T cells. T cells are a type of white blood cell that helps the body fight infection.

The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: antibodies and T cells. Both antibodies and T cells have been used to treat patients with cancers. They have shown promise but have not been strong enough to cure most patients.

We have found from previous research that we can put a new gene into T cells that will make them recognize cancer cells and kill them. In our last clinical trial we made a gene called a chimeric antigen receptor (CAR) from an antibody that recognizes GD2, a substance found on almost all neuroblastoma cells (GD2-CAR). We put this gene into the patients' own T cells and gave them back to 11 neuroblastoma patients. We saw that the cells did grow for a while, but started to disappear from the blood after 2 weeks. We think that if T cells are able to last longer they may have a better chance of killing GD2 positive tumor cells.

Therefore, in this study we will add a new gene to the GD2 T cells that can cause the cells to live longer. T cells need substances called cytokines to survive and the cells may not get enough cytokines after infusion. We have added the gene C7R that gives the cells a constant supply of cytokine and helps them to survive for a longer period of time.

In other studies using T cells, investigators found that giving chemotherapy before the T cell infusion can improve the amount of time the T cells stay in the body and therefore the effect the T cells can have. This is called lymphodepletion and we think that it will allow the T cells to expand and stay longer in the body, and potentially kill cancer cells more effectively.

The GD2-C7R T cells are an investigational product not approved by the Food and Drug Administration.

The purpose of this study is to find the largest safe dose of GD2-C7R T cells, and also to evaluate how long they can be detected in the blood and what affect they have on cancer.

To prepare the T cells (GD2-C7R T cells), research staff will take some blood from the patient. We will grow the GD2.C7R T cells by infecting the T cells with a retroviral vector (a special virus that can carry a new gene into cells) containing one gene that can recognize and kill cancer cells (GD2.CAR) and the new gene called C7R that will help these cells survive longer. After the new genes have been put into the T cells, the cells will be tested to make sure that they kill GD2-positive cancer cells.

Because we are growing the cells in the laboratory, we will also need to take blood to test for infectious viruses such as hepatitis and HIV (the virus that causes AIDS), and we will also ask patients to complete a questionnaire that is given to blood donors.

The cells generated will be frozen and stored to give back to the patient. Because patients will have received cells with a new gene in them patients will be followed for a total of 15 years to see if there are any long term side effects of gene transfer.

Patients will be assigned a dose of GD2-C7R T cells. The assigned dose of cells is based on body weight and height.

In this study, patients will receive the GD2-C7R cells and may also receive cyclophosphamide and fludarabine. These two drugs are standard chemotherapy medicines and may be given before the T cells to make space in the blood for the T cells to grow after receiving them.

If the patient receives cyclophosphamide and fludarabine, these drugs will be given intravenously (through an i.v. needle inserted in a vein or a central line) for 2 days and then fludarabine alone on the third day.

The patient will be given an injection of GD2-C7R T cells into the vein through an IV line at the assigned dose. Before receiving the T cell infusion, the patient may be given a dose of Benadryl (diphenhydramine) and Tylenol (acetaminophen). The infusion will take between 1 and 10 minutes. We will then monitor the patient in the clinic for about 3 hours. If you tolerate the infusion without severe side effects you may receive another infusion one week later. In this case both infusion will be considered part of one dose. The treatment will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital. The patient may need to stay in Houston for up to 4 weeks after the infusion so we can monitor for side effects.

The patient will have follow-up visits after the T cell infusion at weeks 1, 2, 4, 6, and 8, then at months 3, 6, 9, and 12, and then twice a year for the next 4 years and annually for the next 10 years for a total of 15 years. The patient will also have scheduled disease evaluations after the T-cell injection at week 6 and then as clinically needed.

After disease re-evaluation, if the patient's disease has not gotten worse, or if in the future it seems the patient might benefit AND the patient has not had a severe side effect caused by the infusion of the GD2-C7R T cells, the patient may be eligible to receive one additional dose of their T cells. The dose will be at the same dose level as the first infusion and separated by at least 6 weeks such that we can make sure the patient has no severe side effects between infusions. The second dose may consist of two infusions again if you received two infusions with the first dose. If the patient receives an additional dose of GD2-C7R T-cells, then they will need to stay in Houston for up to 4 weeks after the infusion as well so we can monitor for side effects.

Medical tests before treatment--

Before being treated, the patient will receive a series of standard medical tests:

* Physical exam
* Blood tests to measure blood cells, kidney and liver function
* Measurements of the tumor by routine imaging studies and/or bone marrow evaluation. We will use the imaging studies that have been used in the past to best assess the tumor (Computer Tomogram (CT) or Magnetic Resonance Imaging (MRI), and Positron Emission Tomography (PET/CT), Bone Scan, and/or MIBG scan)
* Pulmonary Function Tests (PFT) to see how well your lungs are working

Medical tests during and after treatment--

The patient will receive standard medical tests when they are getting the infusions and afterwards:

* Physical exams
* Blood tests to measure blood cells, kidney and liver function
* Measurements of the tumor by routine imaging studies and/or bone marrow evaluation 6 weeks after the infusion (if the bone marrow showed tumor before the infusion).

To learn more about the way the GD2-C7R T cells are working and how long they last in the body, an extra amount of blood will be obtained on the day that chemotherapy starts, the day of the T-cell infusion(s) and at the end of the T-cell infusion(s), 1, 2, 4, 6 and 8 weeks after the T-cell infusion(s) and every 3 months for the 1st year, every 6 months for the next 4 years and annually for the next 10 years. The amount of blood taken will be based on weight with up to a maximum of 60 ml (12 teaspoons) of blood to be obtained at any one time. For children, the total amount of blood drawn will not be more than 3 ml (less than 1 teaspoon) per 1 kg of body weight on any one day. This volume is considered safe, but may be decreased if the patient is anemic (has a low red blood cell count).

During the time points listed above, if the GD2-C7R T cells are found in the patient's blood at a certain amount, an extra 5 ml (about 1 teaspoon) of blood may need to be collected for additional testing.

If the patient has a procedure where tumor samples are obtained, like a repeat bone marrow evaluation or tumor biopsy, we will request a sample to be used for research purposes.

The patient will receive supportive care for any acute or chronic toxicities, including blood components or antibiotics, and other intervention as appropriate.

C7R-GD2.CART Cells for Patients With Relapsed or Refractory Neuroblastoma and Other GD2 Positive Cancers (GAIL-N)

Phase I Study of Autologous T Lymphocytes Expressing GD2-specific Chimeric Antigen and Constitutively Active IL-7 Receptors for the Treatment of Patients With Relapsed or Refractory Neuroblastoma and Other GD2 Positive Solid Cancers(GAIL-N)

Toxicity will be evaluated as per the NCI CTCAE version 5.0 with the exception of CRS and neurological toxicities that are related to T-cell infusions.

Number of patients with evaluable/measurable disease who have a partial or complete response according to standard disease evaluation criteria

Center for Cell and Gene Therapy, Baylor College of Medicine

The Methodist Hospital Research Institute

Cancer Prevention Research Institute of Texas

Baylor College of Medicine

Assistant Professor

Amino Acids

Lysine

Part 1: Initial cohort of INCB059872 administered every other day (QOD) at the protocol-defined starting dose, with subsequent cohort dose escalation based on protocol-defined criteria. Part 2: Expansion with the recommended dose from Part 1.

INCB059872

Fred Zheng, MD

The purpose of this study is to evaluate the safety and preliminary antitumor activity of INCB059872 in participants with Ewing sarcoma who are refractory or relapsed from prior standard therapy and not eligible for further standard systemic therapy.

A Study of INCB059872 in Relapsed or Refractory Ewing Sarcoma

An Open-Label Phase 1b Study of the Safety, Tolerability, and Preliminary Antitumor Activity of INCB059872 in Participants With Relapsed or Refractory Ewing Sarcoma

Defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of a drug in humans, whether or not considered drug-related.

Defined as the percentage of participants who have a complete response or partial response as determined by investigator assessment of response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Defined as maximum observed plasma concentration.

Defined as time to maximum concentration.

Defined as apparent terminal-phase disposition half-life.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cabozantinib With Topotecan-Cyclophosphamide	NCT04661852	Relapsed Ewing ... Refractory Ewin... Relapsed Osteos... Refractory Oste...	Cabozantinib Topotecan Cyclophosphamid... Myeloid growth ...	6 Years - 30 Years	Dana-Farber Cancer Institute
Study of Lurbinectedin Monotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Ewing Sarcoma	NCT05734066	Refractory Ewin... Relapsed Ewing ... Ewing Sarcoma	Lurbinectedin	2 Years - 30 Years	Jazz Pharmaceuticals
C7R-GD2.CART Cells for Patients With Relapsed or Refractory Neuroblastoma and Other GD2 Positive Cancers (GAIL-N)	NCT03635632	Relapsed Neurob... Refractory Neur... Relapsed Osteos... Relapsed Ewing ... Relapsed Rhabdo... Uveal Melanoma Phyllodes Breas...	C7R-GD2.CART ce...	1 Year - 74 Years	Baylor College of Medicine
A Study of INCB059872 in Relapsed or Refractory Ewing Sarcoma	NCT03514407	Relapsed Ewing ...	INCB059872	12 Years -	Incyte Corporation

Spots Global Cancer Trial Database for relapsed ewing sarcoma