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Adenocarcinoma of the ProstatePhase 2NCT01533246

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

A Phase 2 study testing linsitinib and laboratory biomarker analysis in people with Adenocarcinoma of the Prostate and Hormone-resistant Prostate Cancer, run by National Cancer Institute (NCI) at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
linsitinib and laboratory biomarker analysis
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
2 sitesUnited States
Study dates
Feb 2012to Nov 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed adenocarcinoma of the prostate
  • Surgically or medically castrated, with testosterone levels of < 50 ng/dL (< 2.0 nM); if the patient is being treated with luteinizing hormone-releasing hormone (LHRH) agonists (patient who has not undergone orchiectomy), this therapy must have been initiated at least 4 weeks prior to course 1 Day 1 and must be continued throughout the study
  • Metastatic disease documented by positive bone scan or metastatic lesions other than liver or visceral metastasis on computed tomography (CT) or magnetic resonance imaging (MRI); if lymph node metastasis is the only evidence of metastasis, it must be ≥ 2 cm in diameter
  • Prostate cancer progression documented by PSA according to PCWG2 or radiographic progression according to modified RECIST criteria
  • Asymptomatic or mildly symptomatic from prostate cancer; a score of 0-1 on Brief Pain Inventory (BPI)-Short Form (SF) Question #3 (worst pain in last 24 hours) will be considered asymptomatic, and a score of 2-3 will be considered mildly symptomatic
  • Patients who received combined androgen blockade or received second-line anti-androgen in the context of CRPC must have shown PSA progression after discontinuing the anti-androgen prior to enrollment (≥ 4 weeks since last flutamide, ≥ 6 weeks since last bicalutamide or nilutamide) and have progressive disease
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  • No patients with known brain metastases
  • Understand and voluntarily sign an informed consent form
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Hemoglobin ≥ 10.0 g/dL independent of transfusion
  • Absolute neutrophil count ≥ 1,500/mcL
  • Platelet count ≥ 100,000/μL
  • Serum albumin ≥ 3.5 g/dL
  • Serum creatinine < 1.5 times upper limit of normal (ULN) OR a calculated creatinine clearance ≥ 60 mL/min
  • Serum potassium ≥ 3.5 mmol/L
  • Serum bilirubin < 1.5 times ULN (except for patients with documented Gilbert's disease)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 times ULN
  • Able to swallow the study drug
  • Life expectancy of at least 6 months
  • Men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
  • No history of clinically significant heart disease as evidenced by myocardial infarction or arterial thrombotic events in the past 6 months, severe or unstable angina, New York Heart Association (NYHA) Class II-IV heart disease, or cardiac ejection fraction measurement of < 50% at baseline
  • No prolonged QTc > 470 msec (mean QTc with Bazett's correction) or history of familial long QT syndrome
  • No other malignancy, except non-melanoma skin cancer, with a ≥ 30% probability of recurrence within 24 months
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to OSI-906
  • No uncontrolled intercurrent illness including, but not limited to, psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with insulin-dependent diabetes are excluded
  • Patients with known history of HIV on combination antiretroviral therapy are ineligible
  • Patients with known infectious hepatitis A, B, or C are ineligible
  • No condition that, in the opinion of the investigator, would preclude participation in this trial
  • See Disease Characteristics
  • Prior therapy with ketoconazole and steroids is allowed provided patients have been off treatment for 4 weeks
  • Prior investigational agents with novel adrenal inhibitors (i.e., Abiraterone or TAK700) are allowed provided these agents have been discontinued at least 4 weeks prior to enrollment
  • Prior investigational agents with novel antiandrogens (i.e., MDV 3100) are allowed provided these agents have been discontinued at least 6 weeks prior to enrollment
  • Prior therapy with Sipuleucel-T is allowed provided patients have documented evidence of disease progression as stated above
  • Patients receiving any other hormonal therapy, including any dose of Megestrol acetate (Megace), Proscar (finasteride), any herbal product known to decrease PSA levels (e.g., Saw Palmetto and PC-SPES), or any systemic corticosteroid must discontinue the agent for at least 4 weeks prior to enrollment; progressive disease (as defined above) must be documented after discontinuation of the hormonal therapy
  • Patients on stable doses of bisphosphonates that show subsequent tumor progression may continue on this medication at the discretion of the treating physician; however, patients are not allowed to initiate bisphosphonate therapy within 4 weeks prior to starting therapy or throughout the study
  • No prior systemic chemotherapy for CRPC; prior neoadjuvant and adjuvant chemotherapy are allowed when completed at least 12 months prior to enrollment
  • No use of opiate analgesics for cancer-related pain, including codeine and dextropropoxyphene, currently or anytime within 4 weeks of Cycle 1 Day 1
  • No prior use of IGF-1R inhibitors (monoclonal antibody or small molecule)
  • No palliative radiation therapy to bone metastasis or radionuclide therapy for treatment of metastatic CRPC within 4 weeks of Cycle 1 Day 1
  • Use of the potent CYP1A2 inhibitors ciprofloxacin and fluvoxamine are prohibited
  • Other less potent CYP1A2 inhibitors/inducers are not excluded
  • Supplements or complementary medicine/botanicals are not permitted while on protocol therapy, except for any combination of the following:
  • Conventional multivitamin supplements
  • Selenium
  • Lycopene
  • Soy supplements
  • The use of concomitant steroids is not allowed unless patients are receiving physiological replacement disease for documented adrenal insufficiency
  • Use of drugs that have a known risk of causing Torsades de Pointes (TdP) are prohibited within 14 days prior to study enrollment

Who cannot join

None listed.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44106

  • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44195

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
linsitinib, laboratory biomarker analysis
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • linsitinibDrug

    Also called OSI-906

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

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01533246
Study groupRoleWhat they receive
Treatment (linsitinib)ExperimentalPatients 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.
Receives: Drug: linsitinib; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. PSA Response Analyzed Using the PCWG2 Definition

    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.

    Measured: 12 weeks

Secondary outcomes (5)

  1. Incidence of Toxicities Based on CTCAE Version 4.0 Criteria

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

    Measured: Up to 2 years

  2. Number of Patients With Bidimensional Measurable Disease RECIST-based Response

    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.

    Measured: Up to 2 years

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

    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.

    Measured: assessed up to 12 weeks

  4. Overall Survival Based on the RECIST v1.1

    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).

    Measured: Up to 2 years

  5. Progression Free Survival

    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.

    Measured: assessed up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Feb 2012 (estimated)
  2. Study startFeb 2012
  3. Primary completionNov 2012
  4. Study completionNov 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01533246
Sponsor's protocol ID
NCI-2012-00247
Other IDs
NCI-2012-00247, CDR0000724845, CASE 6810, 8872, U01CA062502
Status last verified
Dec 2013
First submitted
10 Feb 2012
Last updated
13 Mar 2015

Publications

  • Barata P, Cooney M, Tyler A, Wright J, Dreicer R, Garcia JA. A phase 2 study of OSI-906 (linsitinib, an insulin-like growth factor receptor-1 inhibitor) in patients with asymptomatic or mildly symptomatic (non-opioid requiring) metastatic castrate resistant prostate cancer (CRPC). Invest New Drugs. 2018 Jun;36(3):451-457. doi: 10.1007/s10637-018-0574-0. Epub 2018 Feb 23.

    PubMed 29476383

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing linsitinib and laboratory biomarker analysis in people with Adenocarcinoma of the Prostate and Hormone-resistant Prostate Cancer, run by National Cancer Institute (NCI) at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 49 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PSA Response Analyzed Using the PCWG2 Definition (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01533246, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2015.

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