Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Prostatic Neoplasms

Adenocarcinoma

Recurrence

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Analgesics

All Drugs and Chemicals

Analgesics, Non-Narcotic

Patients receive linsitinib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo serum and plasma sample collection at baseline, on day 1 of courses 2 and 4, and after completion of study treatment for correlative studies.

Oral Linsitinib 150mg, twice a day, days 1- 28

linsitinib

laboratory biomarker analysis

Jorge Garcia

This phase II trial studies how well linsitinib works in treating patients with asymptomatic or mild symptomatic metastatic prostate cancer. Linsitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To evaluate time to prostate-specific antigen (PSA) progression based on Prostate Cancer Working Group (PCWG2) criteria.

II. To evaluate PSA response (proportion of patients achieving a PSA decline \> 50% according to PCWG2 criteria in patients receiving linsitinib \[OSI-906\]).

III. To evaluate overall response rate (ORR) in patients with Response Evaluation Criteria in Solid Tumors (RECIST)-defined measurable disease receiving OSI-906.

SECONDARY OBJECTIVES:

I. To evaluate the effect of OSI-906 on time-to opiate use for cancer pain. II. To evaluate the effect of OSI-906 on radiographic progression-free survival (rPFS) of patients with asymptomatic or mildly symptomatic (non-opioid requiring) castrate-resistant prostate cancer (CRPC).

III. To evaluate the overall survival (OS) of patients with asymptomatic or mildly symptomatic (non-opioid requiring) CRPC receiving OSI-906.

IV. To further evaluate the safety of OSI-906 in patients with asymptomatic or mildly symptomatic (non-opioid requiring) CRPC.

TERTIARY OBJECTIVES:

I. To describe the effects of OSI-906 in the levels of androstenedione, dehydroepiandrostenedione (DHEA), DHEA-sulfate, p insulin-like growth factor-1 receptor (IGF-IR), and p-insulin receptor (IR). (Exploratory) II. To describe the effects of OSI-906 in the levels of transforming growth factor (TGF)-beta (b1), interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha (a), and monocyte chemotactic protein 1 (MCP-1) as markers of metastatic progression. (Exploratory) III. To describe the effects of OSI-906 on the number of circulating tumor cells (CTCs) and endothelial cells (CECs). (Exploratory) IV. To use ribonucleic acid (RNA) extracted from CTCs to evaluate effects on downstream targets of IGF-1R signaling after OSI-906 treatment. (Exploratory) V. To measure the effect of OSI-906 on the expression of IGF-1R on CTCs. (Exploratory)

OUTLINE:

Patients receive linsitinib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo serum and plasma sample collection at baseline, on day 1 of courses 2 and 4, and after completion of study treatment for correlative studies.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

Linsitinib in Treating Patients With Asymptomatic or Mildly Symptomatic Metastatic Prostate Cancer

A Phase 2 Study of OSI-906 in Patients With Asymptomatic or Mildly Symptomatic (Non-Opioid Requiring) Metastatic Castrate Resistant Prostate Cancer (CRPC)

Number of patients with a PSA Response will be evaluated according to the recommendations from National Cancer Institute Prostate-Cancer Working Group 2 (PCWG2) criteria. PSA decline of at least 50% from baseline confirmed by a second measurement at least 4 weeks later.

Number of patients with at least possibly related to treatment toxicities grade 3 or higher based on Common Terminology Criteria for Adverse Events.

RECIST response categories: Progressive disease (PD): \>=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): \>=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.

TTPP will be measured from protocol registration to appearance of PSA progression as defined by the criteria of the PSA Working Group response criteria. The end point for progression will be calculated at the time a 25% increase in PSA has been achieved.

The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

Progression Free survival (PFS) time was measured as the time from the date of on study up to the date of occurrence of the first event defining a disease progression or death due to any cause, whichever occurred first.

National Cancer Institute (NCI)

Patients receive linsitinib 150mg, PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo serum and plasma sample collection at baseline, on day 1 of courses 2 and 4, and after completion of study treatment for correlative studies.

linsitinib: Given PO

laboratory biomarker analysis: Correlative studies

Treatment (Linsitinib)

Patients receive linsitinib 150mg PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo serum and plasma sample collection at baseline, on day 1 of courses 2 and 4, and after completion of study treatment for correlative studies.

linsitinib: Given PO

laboratory biomarker analysis: Correlative studies

50-59 years

60-69 years

70-79 years

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Jorge Garcia

PSA Partial Response

PSA No Response

PSA Response Analyzed Using the PCWG2 Definition

Incidence of Toxicities Based on CTCAE Version 4.0 Criteria

Partial Response

Stable Disease

Progression

Number of Patients With Bidimensional Measurable Disease RECIST-based Response

Time to PSA Progression (TTPP) Analyzed Using the PCWG2 Definition

Overall Survival Based on the RECIST v1.1

Progression Free Survival

Overall Study

Antineoplastic Agents

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Amino Acids

Paclitaxel

Dexamethasone

Albumin-Bound Paclitaxel

Bortezomib

Dexamethasone acetate

BB 1101

Erlotinib Hydrochloride

Tubulin Modulators

Antimitotic Agents

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Arm A includes subjects from Protocol OSI-906-301

Arm B includes subjects from Protocol OSI-906-205

Arm C includes subjects from Protocol OSI-906-205 and OSI-906-207

Arm D includes subjects from Protocol OSI-906-202

Arm E includes subjects from Protocol OSI-906-202, linsitinib on Days 1-3 of each week plus weekly paclitaxel

Arm F includes subjects from Protocol OSI-906-202

Arm G includes subjects from Protocol OSI-906-103

includes subjects from protocols SARC 022/CTEP 8945, linsitinib x28 days (each cycle)

includes subjects from EuroSARC protocol, linsitinib on Days 1-3; Days 8-10 and Days 15-17

includes subjects from protocol MM-001; Days 1, 4, 8 \& 11 (cycles 1-8) and Days 1, 8, 15 \& 22 (cycles 9+)

erlotinib

paclitaxel

Executive Medical Director

The purpose of this study is to provide access to continued treatment for subjects who participated in other Astellas sponsored trials and for whom the investigator feels the subject may benefit from continued treatment.

A Rollover Study for Subjects That Have Participated in an Astellas Sponsored Linsitinib Trial

A Phase II Open-label Rollover Study for Subjects That Have Participated in an Astellas Sponsored Linsitinib Trial

Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."

Astellas Pharma Global Development, Inc.

Digestive System Diseases

Heart and Blood Diseases

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Rare Diseases

Gastrointestinal Stromal Tumors

Paraganglioma

Chondrosarcoma

Carney Complex

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Sarcoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Myxoma

Heart Neoplasms

Thoracic Neoplasms

Heart Diseases

Congenital Abnormalities

Abnormalities, Multiple

Skin Abnormalities

Paragangliomas 1

Soft Tissue Sarcoma

Neuroendocrine Tumor

Neuroepithelioma

Heart Tumor

Patients receive linsitinib 150mg orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Linsitinib

Pharmacological Study

Margaret von Mehren

This phase II trial studies how well linsitinib works in treating younger and adult patients with gastrointestinal stromal tumors. Linsitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To determine the response rate to treatment with OSI-906 (linsitinib) 150mg BID in patients with advanced wild-type (WT) gastrointestinal stromal tumor (GIST).

SECONDARY OBJECTIVES:

I. To determine the clinical benefit rate (CBR) (stable disease \[SD\] \>= 9 months, partial response \[PR\], or complete response \[CR\]) in patients with advanced WT GIST treated with OSI-906.

II. To determine the response duration, progression free survival (PFS), and overall survival (OS) in patients with advanced WT GIST treated with OSI-906.

III. To determine the tolerability and adverse event profile of OSI-906 in patients with advanced GIST.

IV. To explore patterns of protein expression in serum and tumor tissues as predictors of response and progression-free survival (PFS) in advanced WT GIST treated with OSI-906.

V. To evaluate the metabolic response to OSI-906 using fludeoxyglucose F 18 (FDG)-positron emission tomography (PET).

VI. To determine if tumor metabolic response correlates with anatomic response and clinical benefit.

VII. To measure changes in tumor metabolism by FDG-PET qualitatively and semi-quantitatively with standard uptake value (SUV) and tumor body ratio (TBR) from baseline to first computed tomography (CT)-response evaluation and correlate the findings with size changes as defined by conventional cross-sectional imaging scans.

VIII. To investigate correlations between glucose, insulin, and candidate tumor tissue and blood biomarkers with FDG-PET metabolic response.

OUTLINE:

Patients receive linsitinib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days, every 12 weeks for 2 years, and then annually thereafter.

Linsitinib in Treating Patients With Gastrointestinal Stromal Tumors

A Phase 2 Study of Linsitinib (OSI-906) in Pediatric and Adult Wild Type Gastrointestinal Stromal Tumors

Time to progression will be evaluated using cumulative incidence.

To determine if the number of participants with tumor metabolic response correlates with anatomic response and clinical benefit.

Determine the response rate, Complete Response (CR) or Partial Response (PR), to treatment with linsitinib (OSI-906) in patients with advanced wild-type (WT) gastrointestional stromal tumor (GIST) as determined by RECIST 1.1.

Prolonged non-progression is of clinical benefit (CR + PR + SD at 9 months).

Analyzed using Kaplan-Meier curves for the all treated and per protocol populations.

Analyzed using Kaplan-Meier curves for the all treated and per protocol populations

To determine the tolerability and adverse event profile of OSI-906 in patients with advanced GIST.

To explore patterns of protein expression in serum and tumor tissues as predictors of response and progression-free survival in advanced WT GIST treated with OSI-906. All Insulin Growth Factor Receptor (IGFR) and phosphorylated AKT (pAKT) evaluation was performed in a blinded manner. Distribution and intensity of positive tumor cell staining was assessed for these markers. Loss of succinate dehydrogenase complex flavoprotein subunit A (SDHA) protein expression has been correlated with the presence of a mutation in SDHA. Loss of succinate dehydrogenase complex iron sulfur subunit B (SDHB) protein expression occurs from bi-allelic inactivation of any of the succinate dehydrogenase (SDH) subunit genes. Loss of expression of one member of the complex alters the structure or production of SDH proteins such that the complex is no longer able to form. This results in elevated intracellular levels of succinate as well as loss of demethylase activity.

Evaluate the number of participants with metabolic response to OSI-906 using fluorodeoxyglucose positron emission tomography (FDG-PET). Evaluation of metabolic response to linsitinib based on two criteria (EORTC and PERCIST).

To measure changes in tumor metabolism by FDG-PET qualitatively and semi-quantitatively with SUV from baseline to first CT response evaluation and correlate the findings with size changes as defined by conventional cross-sectional imaging scans.

SUVmax determined by: SUVmax = \[VOI activity (mCi/ml) \* body wt (g)\]/injected dose (mCi) SUVpeak determined by identifying the hottest cubic centimeter within a VOI centered on the lesion with the highest FDG.

To investigate correlations between glucose, insulin, tumor tissue and blood biomarkers with FDG-PET metabolic response.

Patients receive linsitinib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Correlative studies

Linsitinib: Given PO

Pharmacological Study: Correlative studies

Age, Categorical

Age, Continuous

Kristen Nuyen, Research Project Manager

Number of Participants With Complete Response or Partial Response Using Response Evaluation Criteria in Solid Tumors Guideline Version 1.1

Patients receive linsitinib 150mg PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Correlative studies

Linsitinib: Given PO

Pharmacological Study: Correlative studies

Clinical Benefit Rate Defined as Stable Disease (SD) >= 9 Months, Partial Response (PR) or Complete Response (CR)

Overall Survival (OS)

Progression Free Survival (PFS)

Response Duration

Data was not collected for this outcome measure due to limited activity seen with the study treatment.

Failure-free Survival

Related to study drug

Related to study drug Grade 3 or higher

Patients receive linsitinib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Correlative studies

Linsitinib: Given PO

Pharmacological Study: Correlative studies

285 Adverse Events reported during the study.

Tolerability and Adverse Event Profile of Linsitinib

SDHA deficiency

SDHB deficiency

High to intermediate paKT stain

High expression of IGFR

Intermediate levels of IGFR

Depending on the patient samples available, the available samples varied from 17 to 14.

Patterns of Protein Expression in Serum and Tumor Tissues as Predictors of Response and PFS

Partial metabolic response rate

Stable disease metabolic response rate

Number of Participants With Metabolic Response to Linsitinib Using FDG-PET.

SUVmax

SUVpeak

Changes in Tumor Metabolism by FDG-PET Qualitatively and Semi-quantitatively With Standard Uptake Value (SUV)

Data was not collected in correlation to FDG-PET response results.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Linsitinib in Treating Patients With Asymptomatic or Mildly Symptomatic Metastatic Prostate Cancer	NCT01533246	Adenocarcinoma ... Hormone-resista... Recurrent Prost... Stage IV Prosta...	linsitinib laboratory biom...	18 Years -	National Cancer Institute (NCI)
A Rollover Study for Subjects That Have Participated in an Astellas Sponsored Linsitinib Trial	NCT02057380	Advanced Solid ...	linsitinib erlotinib paclitaxel Bortezomib Dexamethasone	18 Years -	Astellas Pharma Inc
Linsitinib in Treating Patients With Asymptomatic or Mildly Symptomatic Metastatic Prostate Cancer	NCT01533246	Adenocarcinoma ... Hormone-resista... Recurrent Prost... Stage IV Prosta...	linsitinib laboratory biom...	18 Years -	National Cancer Institute (NCI)
Linsitinib in Treating Patients With Gastrointestinal Stromal Tumors	NCT01560260	Carney Complex Chondrosarcoma Gastrointestina... Paraganglioma	Laboratory Biom... Linsitinib Pharmacological...	18 Years -	National Cancer Institute (NCI)
A Rollover Study for Subjects That Have Participated in an Astellas Sponsored Linsitinib Trial	NCT02057380	Advanced Solid ...	linsitinib erlotinib paclitaxel Bortezomib Dexamethasone	18 Years -	Astellas Pharma Inc
Linsitinib or Topotecan Hydrochloride in Treating Patients With Relapsed Small Cell Lung Cancer	NCT01533181	Recurrent Small...	Laboratory Biom... Linsitinib Pharmacological... Topotecan Hydro...	18 Years -	National Cancer Institute (NCI)
Phase I/II Study of Postoperative Adjuvant Chemoradiation for Advanced-Stage Cutaneous Squamous Cell Carcinoma of the Head and Neck (cSCCHN)	NCT01465815	Recurrent Skin ... Recurrent Squam... Squamous Cell C... Stage III Squam... Stage IVA Squam... Stage IVB Squam...	erlotinib hydro... linsitinib placebo radiation thera... therapeutic con... laboratory biom...	18 Years -	OHSU Knight Cancer Institute

Spots Global Cancer Trial Database for linsitinib

Every month we try and update this database with for linsitinib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for linsitinib

Every month we try and update this database with for linsitinib cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for linsitinib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.