Dasatinib, Temsirolimus, and Cyclophosphamide in Treating Patients With Advanced, Recurrent, or Refractory Solid Tumors

NCT02389309 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: 2014-0692NCI-2015-00524P30CA016672
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of dasatinib and temsirolimus when given together with cyclophosphamide in treating patients with solid tumors that have spread to other places in the body, have come back, or have not respond to previous treatment. Dasatinib and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving dasatinib and temsirolimus together with cyclophosphamide may be a better treatment for advanced solid tumors.

Conditions

Advanced Malignant Solid Neoplasm; Recurrent Brain Neoplasm; Recurrent Malignant Solid Neoplasm; Refractory Brain Neoplasm

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) defined as the highest dose level tested at which =< 2/6 patients experience dose limiting toxicities (DLT) graded according to the National Cancer Institute (NCI) Common Toxicity Criteria (CTCAE) version 4.0

  Up to day 35

• Incidence of adverse events (AEs) graded according to NCI CTCAE version 4.0

  AEs will be tabulated by dose, grade, and attribution.

  Up to 28 days post-treatment

Secondary Outcomes (2)

• Best response (complete response [CR], partial response [PR], stable disease [SD], and progressive disease [PD]) using the Response Evaluation Criteria in Solid Tumors from the NCI for assessment of radiographic response

  Up to 4 weeks post-treatment

• Levels of biological markers measured in tissue, blood, or plasma

  Up to 4 weeks post-treatment

Study Arms (1)

Treatment (dasatinib, cyclophosphamide, temsirolimus)

EXPERIMENTAL

Patients receive dasatinib PO BID on days 1-21, cyclophosphamide PO QD on days 1-21, and temsirolimus IV over 30-60 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing stable disease or better may continue treatment with the approval of the Study Chair.

Drug: Cyclophosphamide; Drug: Dasatinib; Other: Laboratory Biomarker Analysis; Drug: Temsirolimus

Interventions

Cyclophosphamide DRUG

Given PO

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (dasatinib, cyclophosphamide, temsirolimus)

Dasatinib DRUG

Given PO

Also known as: BMS-354825, Sprycel

Treatment (dasatinib, cyclophosphamide, temsirolimus)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (dasatinib, cyclophosphamide, temsirolimus)

Temsirolimus DRUG

Given IV

Also known as: CCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin Analog, Rapamycin Analog CCI-779, Torisel

Treatment (dasatinib, cyclophosphamide, temsirolimus)

Eligibility Criteria

• Age: 12 Months - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must be \>/= 12 months and \< 21 years of age at the time of study enrollment.
• Patients must have had a previous histological verification of a solid tumor at the original diagnosis and/or recurrence including brain tumors; for patients with brain stem gliomas and optic pathway tumors, the requirement for histological evaluation may be waived; the patient's disease must be considered refractory to conventional/standard therapy, or a disease for which no conventional therapy exists and is progressive
• The patient must have a stable clinical (neurologic in case of brain tumors) exam and be on a stable dose of steroids for at least 1 week prior to study entry; the patient should have a measurable and/or evaluable disease; measurable disease which is defined as the presence of at least one lesion that can be accurately measured in two dimensions (each measures at least 10 mm) or evaluable disease which is defined as at least one lesion that can be accurately measured in at least one dimension (measure at least 10 mm)
• Karnofsky performance status \>= 50 for patients \>= 16 years of age and a Lansky performance status \>= 50 for patients aged \< 16 years
• Life expectancy: must be \>= 12 weeks
• Chemotherapy:
• Must not have received myelosuppressive chemotherapy within 3 weeks of the study entry (6 weeks if prior nitrosourea); prior treatment with either dasatinib or temsirolimus but not both is allowed; at least 3 weeks must have elapsed from the last dose
• Biologic therapy (anti-neoplastic)
• Must not have received oral tyrosine kinase inhibitors (other than dasatinib) or other similar agents within 3 weeks of the study entry and all toxicities must have resolved to \< grade 2 prior to enrollment
• Must not have received bevacizumab or other monoclonal antibody therapy within 4 weeks of study the entry
• Radiotherapy (XRT): at least 4 weeks for focal XRT or 8 weeks for craniospinal XRT must have elapsed prior to study entry
• Stem cell transplant (SCT): at least 8 weeks following autologous SCT and 12 weeks for allogeneic SCT
• Surgery: at least 2 weeks following surgery including brain and spine provided post-operative magnetic resonance imaging (MRI) shows no active bleeding
• Concomitant medications: the following drugs need to be stopped at the time of beginning therapy: patient cannot be on liver enzyme inducing anticonvulsants; patients must not have received growth factors to support the number or function of white cells or platelets within the past 7 days and pegfilgrastim within the past 14 days; patients must not be receiving any anti-thrombotic or anti-platelet agents; patient cannot be on drugs that cause significant prolonged QT (category I drug)
• Absolute neutrophil count (ANC) greater than or equal to 1000/mm\^3

You may not qualify if:

• Patients with evidence of recent intratumoral hemorrhage (within 3 months of study enrollment), gastrointestinal bleeding, history of coronary artery disease or on anticoagulation therapy
• Pregnant or breast-feeding women will not be entered on this study
• Uncontrolled current illness including, but not limited to, uncontrolled infection, need for hemodialysis, need for ventilatory support, psychiatric illness/social situations that would limit compliance with study requirements
• History of hypersensitivity to any component of the formulation
• Patients with known human immunodeficiency virus (HIV) are ineligible for this study
• Patients must not have received prior therapy with dasatinib and temsirolimus for any indication
• Patients with clinically significant cardiovascular disease: history of ischemic or hemorrhagic stroke within past 6 months; uncontrolled hypertension, on at least 2 repeated determinations on separate days within past 3 months; myocardial infarction or unstable angina within past 6 months; New York Heart Association grade III or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris within past 6 months; clinically significant peripheral vascular disease within past 6 months; pulmonary embolism, deep vein thrombosis (DVT), or other thromboembolic event within past 6 months; diagnosed congenital long QT syndrome; any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes); prolonged QTc interval on pre-entry electrocardiogram (\> 450 msec); subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration
• Anticonvulsants: patients on enzyme inducing anticonvulsants (EIAED) will be excluded; if patients were previously on EIAEDs that have been discontinued, patients must have been off EIAEDs for \>= 2 weeks prior to initiation of dasatinib
• Anticoagulants/anti-platelets: patients on therapeutic (treatment) dose of anticoagulants (e.g. warfarin, low molecular-weight heparin) are not eligible; patients are not allowed to take aspirin, clopidogrel, ticlopidine, Aggrenox; patients on prophylactic anticoagulation may be enrolled and treated on study as long as their platelet count is monitored closely and maintained at \> 75,000 while they are receiving dasatinib
• Inducers and Inhibitors of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4): patients required to be on any CYP3A4/5 inhibitors or inducers will be excluded (with the exception of dexamethasone, but all efforts should be made to reduce the dose of dexamethasone); patients must discontinue drug at least 7 days prior to starting dasatinib
• Angiotensin-converting enzyme (ACE) inhibitors: patients who are currently receiving ACE inhibitors are not eligible
• Anti-graft-versus-host disease (GVHD) or agents to prevent organ rejection post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial
• Category I drugs that are generally accepted to have a risk of causing torsades de pointes including: (patients must discontinue drug at least 7 days prior to starting dasatinib)
• Quinidine, procainamide, disopyramide
• Amiodarone, sotalol, ibutilide, dofetilide

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Cyclophosphamide; Dasatinib; temsirolimus; Sirolimus

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Macrolides; Lactones

Study Officials

• Wafik T Zaky

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2015
• First Posted: March 17, 2015
• Study Start: October 5, 2015
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027
• Last Updated: March 9, 2026

Record last verified: 2026-03

Locations

US (1)