Antineoplastic Agents

All Drugs and Chemicals

TIC10 compound

Patients receive oral ONC201 PO on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Oral ONC201

pharmacological study

laboratory biomarker analysis

Jyoti Malhotra

This phase I trial studies the long-term side effects of the continuation of oral ONC201 in treating patients with solid tumors that have spread to other places in the body who have previously benefited from receiving this drug. Oral ONC201 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To evaluate the long-term safety and tolerability of ONC201 (oral ONC201) administered orally in patients with advanced cancers.

SECONDARY OBJECTIVES:

I. To characterize pharmacokinetics of ONC201. II. To assess serum biomarkers of therapeutic response to ONC201. III. To assess preliminary antitumor activity of ONC201 as a single agent in advanced solid tumors.

OUTLINE:

Patients receive oral ONC201 orally (PO) on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks.

Continuation of Oral ONC201 in Treating Patients With Advanced Solid Tumors

A Continuation Clinical Trial of Every Three-Week Dosing of Oral ONC201 in Patients With Advanced Solid Tumors

An adverse experience is defined as any unintended or abnormal clinical observation that is not of benefit to the patient. Either the condition was not present prior to exposure to the study therapy, or it has worsened in intensity or frequency following exposure to the study therapy. Descriptive statistics will be provided.

The oral ONC201 concentration, and the corresponding time, area under the curve, elimination half-life, total body clearance and volume of distribution will be determined for each patient concentration-time data using a non-compartmental model. Descriptive statistics will be provided.

Descriptive statistics on continuous data will include means, medians, standard deviations, and ranges will be provided to estimate clinical benefit rate.

National Cancer Institute (NCI)

Rutgers Cancer Institute of New Jersey

Oncoceutics, Inc.

Rutgers, The State University of New Jersey

Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Neoplastic Processes

Hematinics

Liver Extracts

Patients undergo either percutaneous placement of metallic fiducial markers within the liver or respiratory-correlated cone-beam computed tomography for stereotactic targeting and planning. Patients then undergo single-fraction stereotactic body radiotherapy over approximately 1 hour within 1 week of the marker placement.

Patients undergo stereotactic body radiation therapy

stereotactic radiation therapy

implanted fiducial-based imaging

cone-beam computed tomography

Robert C. Miller, M.D.

RATIONALE: Stereotactic radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue.

PURPOSE: This phase I/II trial is studying the side effects and best dose of stereotactic radiation therapy in treating patients with liver metastases.

OUTLINE: This is a phase I/II, dose-escalation study.

Phase I: Patients undergo either percutaneous placement of metallic fiducial markers within the liver or respiratory-correlated cone-beam computed tomography for stereotactic targeting and planning. Patients then undergo single-fraction stereotactic body radiotherapy over approximately 1 hour within 1 week of the marker placement.

Phase II: Patients undergo treatment as in phase I at the maximum tolerated dose. After completion of study treatment, patients will be followed at weeks 4 and 12 and then every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Stereotactic Radiation Therapy in Treating Patients With Liver Metastases

A Phase I/II Dose-Finding Study of Single-Fraction Stereotactic Body Radiotherapy (SF-SBRT) for the Treatment of Liver Metastases

LC is defined as no evidence of disease progression within the volume treated to prescription dose (i.e. PTV) for a specific lesion. The development of new intrahepatic metastases sites outside of the PTV will not be considered local failures.

Number of patients with a grade \>= 3 adverse event.

Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.

Description of Grades:

Grade 1: Mild Grade 2: Moderate Grade 3: Severe Grade 4: Life-threatening Grade 5: Death

Mayo Clinic

Arm I

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Dr. Robert C. Miller

Not enough patients were accrued to the Phase I portion to determine the MTD.

Determination of the Maximum Tolerated Dose (MTD) of Single-fraction Stereotactic Body Radiation Therapy (SF-SBRT) in Hepatic Metastases.

No patients were accrued to the Phase II portion.

Determine the Minimum Effective Dose (MED) Necessary for Durable Local Control, Defined as the Dose Level at Which Local Control (LC) is >= 80% at 1 Year. (Phase II)

Toxicity and Adverse Events Profile (Phase I)

Patient Clinical Response and Treatment Effects on Blood Chemistry and Hepatic Function Markers (Phase I)

Radiographic Response Rate (Phase II)

Local Control (LC) Cumulative Incidence Rates (Phase II)

Median Time to Progression of Treated Tumors (Phase II)

Refinement of Toxicity and Adverse Events Profile (Phase II)

Refinement of Patient Clinical Response and Treatment Effects on Blood Chemistry and Hepatic Function Markers (Phase II)

Evaluation of Cause of Death (Phase II)

Overall Study

Irinotecan

Temozolomide

Talazoparib

Poly(ADP-ribose) Polymerase Inhibitors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients receive PARP inhibitor BMN-673 PO QD on days 1-28 and temozolomide PO daily on days1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients receive PARP inhibitor BNM-673 as in Arm A and irinotecan hydrochloride IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PARP inhibitor BMN-673

temozolomide

irinotecan hydrochloride

Zev Wainberg

This phase I trial studies the side effects and the best dose of poly (adenosine diphosphate \[ADP\]-ribose) polymerase (PARP) inhibitor BMN-673 when given together with temozolomide or irinotecan hydrochloride in treating patients with locally advanced or metastatic solid tumors. PARP inhibitor BMN-673 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and may help temozolomide and irinotecan hydrochloride work better by making tumor cells more sensitive to the drug. Drugs used in chemotherapy, such as temozolomide and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving PARP inhibitor BMN-673 with temozolomide or irinotecan hydrochloride may be an effective treatment for patients with advanced solid tumors.

PRIMARY OBJECTIVES:

I. To assess the safety and tolerability and to estimate the maximum tolerated dose (MTD) of the following combinations in participants with advanced solid tumors: Arm A: BMN 673 (PARP inhibitor BMN-673) and temozolomide; Arm B: BMN 673 and irinotecan (irinotecan hydrochloride).

SECONDARY OBJECTIVES:

I. To evaluate the pharmacokinetics of BMN 673, temozolomide, and irinotecan when BMN 673 is given in combination with temozolomide (Arm A) or irinotecan (Arm B). To assess the effects of temozolomide and irinotecan in Arms A and B respectively on the pharmacokinetics of BMN 673.

II. To evaluate biomarkers that correlate with effect of BMN 673 in combination with temozolomide or irinotecan.

III. To document any anti-tumor activity.

OUTLINE: This is a dose-escalation study of PARP inhibitor BMN-673. Patients are assigned to 1 of 2 treatment arms.

ARM A: Patients receive PARP inhibitor BMN-673 orally (PO) once daily (QD) on days 1-28 and temozolomide PO daily on days1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive PARP inhibitor BNM-673 as in Arm A and irinotecan hydrochloride intravenously (IV) on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 12 months.

PARP Inhibitor BMN-673 and Temozolomide or Irinotecan Hydrochloride in Treating Patients With Locally Advanced or Metastatic Solid Tumors

Phase I Trial of BMN 673 and Selected Cytotoxics in Patients With Advanced Solid Tumors

Characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy.

Characterized by type, frequency, severity, timing, seriousness and relationship to study therapy.

Sum of partial responses plus complete responses. The proportion of ever achieving a clinical response will be estimated, and an exact one-sided 90% confidence interval will be constructed to identify the likely range for the underlying tumor response rate.

The log rank test will be used to examine association between categorical markers and time to disease progression. Cox-proportional hazards regression models will be used to correlate quantitative markers with time to disease progression.

Translational Research in Oncology

BioMarin Pharmaceutical

Medivation, Inc.

Jonsson Comprehensive Cancer Center

Capecitabine

Antimetabolites

capecitabine

enzastaurin hydrochloride

Carolyn Britten, MD

RATIONALE: LY317615 may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth and by stopping blood flow to the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining LY317615 with capecitabine may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining LY317615 with capecitabine in treating patients who have advanced solid tumors.

OBJECTIVES:

* Determine the maximum tolerated dose and the recommended phase II dose of LY317615 and capecitabine in patients with advanced solid tumors.
* Determine the safety profile of this regimen in these patients.
* Determine the pharmacokinetics of this regimen in these patients.
* Determine, preliminarily, the antitumor activity of this regimen in these patients.
* Determine the effects of LY317615 on potential angiogenic surrogate markers in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive oral LY317615 daily on days 1-14 (course 1 only). Beginning with course 2, patients receive oral LY317615 daily on days 1-21 and oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of LY317615 and capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are treated at the recommended phase II dose.

Patients are followed at 30 days after the last dose of study drug.

PROJECTED ACCRUAL: A total of 12-36 patients will be accrued for this study.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Continuation of Oral ONC201 in Treating Patients With Advanced Solid Tumors	NCT02324621	Unspecified Adu...	Oral ONC201 pharmacological... laboratory biom...	18 Years -	Rutgers, The State University of New Jersey
Stereotactic Radiation Therapy in Treating Patients With Liver Metastases	NCT00938457	Unspecified Adu...	stereotactic ra... implanted fiduc... cone-beam compu...	18 Years - 120 Years	Mayo Clinic
PARP Inhibitor BMN-673 and Temozolomide or Irinotecan Hydrochloride in Treating Patients With Locally Advanced or Metastatic Solid Tumors	NCT02049593	Metastatic Canc... Unspecified Adu...	PARP inhibitor ... temozolomide irinotecan hydr... pharmacological... laboratory biom...	18 Years -	Jonsson Comprehensive Cancer Center
LY317615 Plus Capecitabine in Treating Patients With Advanced Solid Tumors	NCT00052273	Adult Solid Tumor	capecitabine enzastaurin hyd...	18 Years -	Jonsson Comprehensive Cancer Center

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