AzTrials
AzTrials

Advanced Malignant Pleural MesotheliomaPhase 2DOVE-MNCT01769547

A Phase II Study of Single-agent DOVitinib in Advanced Malignant PlEural Mesothelioma Which Has Progressed Following Prior Platinum-Antifolate Chemotherapy

A Phase 2 study testing Dovitinib in people with Advanced Malignant Pleural Mesothelioma and MPM, run by Ontario Clinical Oncology Group (OCOG) at 5 sites in Canada.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This is a single-arm, open label, two stage, phase II study of dovitinib in patients with advanced Malignant Pleural Mesothelioma (MPM). The primary purpose of this study is to evaluate the potential efficacy of dovitinib in the second- or third-line treatment of MPM using progression free survival (PFS). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Malignant Pleural Mesothelioma, MPM
What is being tested?
Dovitinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
5 sitesCanada
Study dates
Mar 2013to Jun 2015
Phase
Phase 2
Are there results?
None posted in the registry

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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Advanced incurable histologically confirmed malignant pleural mesothelioma that has progressed following prior administration of platinum-antifolate based chemotherapy.
  • Measurable disease by RECIST 1.1. For those patients with only pleural rind, measurable disease will be determined using modified RECIST criteria.
  • Availability of archival tissue.

Who cannot join

  • Less than 18 years of age.
  • ECOG performance status > 2.
  • Received > two lines of systemic therapy.
  • Patients who have received the last administration of an anticancer monoclonal antibody, immunotherapy, hormonal therapy, or chemotherapy (except nitrosureas and mitomycin-C) ≤ 4 weeks prior to starting study drug or who have not recovered from the side effects of such therapy.
  • Patients who have received the last administration of nitrosureas or mitomycin-C ≤ 6 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy.
  • Patients who have received radiotherapy ≤ 4 weeks prior to starting the study drug or who have not recovered from radiotherapy-related toxicities (note: palliative radiotherapy for bone lesions ≤ 2 weeks prior to starting study drug is allowed).
Show all 48Show fewer
  • Patients who have undergone major surgery (e.g., intra-thoracic, intra-abdominal, intra-pelvic) ≤ 4 weeks prior to starting study treatment or who have not recovered from side effects of such surgery.
  • Prior use of angiogenesis inhibitors.
  • Patients with another primary malignancy within 3 years prior to starting study treatment, with the exception of adequately treated cancer such as basal cell carcinoma, squamous cell carcinoma, or non-melanomatous skin cancer or in-situ carcinoma of the uterine cervix. (Exception, patients with localized prostate cancer treated within the last 2 years and currently on hormonal therapy).
  • Patients with a history of pulmonary embolism (PE), or untreated deep venous thrombosis (DVT) ≤ 6 months prior to starting study drug.
  • Cirrhosis of the liver or known hepatitis B or C infection that is either acute or is considered chronic because the virus did not become undetectable:
  • Hepatitis C Virus (HCV) infection: acute or chronic infection as depicted by a positive HCV RNA testing (note: in a patient with known anti-HCV but with a negative test for HCV RNA, re-testing for HCV RNA 4-6 months later is requested to confirm the resolution of HCV infection)
  • Hepatitis B Virus (HBV) infection: acute infection (HBsAg+ with or without HBeAg+ or detectable serum HBV DNA), HBV carriers as evidence by ongoing presence of HBsAg and detectable serum HBV DNA levels
  • Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory).
  • Patients who are currently receiving antiplatelet therapy of prasugrel or clopidogrel, or full dose anticoagulation treatment with therapeutic doses of warfarin. However, treatment with low doses of warfarin (e.g., ≤ 2 mg/day) or locally accepted low doses of acetylsalicylic acid (up to 100 mg daily) to prevent cardiovascular events or strokes is allowed. Required use of therapeutic doses of coumarin-derivative anticoagulants such as warfarin, although doses of up to 2mg daily are permitted for prophylaxis of thrombosis. Note: Low molecular weight heparin is permitted provided the patient's PT INR is < 1.5.
  • Urine dipstick reading: Positive for proteinuria or, if documentation of +1 results for protein on dipstick reading, then total urinary protein >500 mg and measured creatinine clearance <50 mL/min/1.73m2 from a 24 hour urine collection.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to dovitinib.
  • Taking medications that are potent CYP3A4 inducers or inhibitors (dovitinib is metabolized primarily by the CYP3A4 liver enzyme, every effort should be made to switch patients taking such agents or substances to other medications).
  • History of cardiac dysfunction with an ECHO or MUGA scan outside the institutional range of normal for patients with impaired cardiac function or clinically significant cardiac disease, including any of the following:
  • History or presence of serious uncontrolled ventricular arrhythmias
  • Clinically significant resting bradycardia
  • LVEF assessed by either 2-D echocardiogram (ECHO) < 50% or lower limit of normal (whichever is the higher), or 2-D multiple gated acquisition scan (MUGA) < 45% or lower limit of normal (whichever is the higher)
  • Any of the following within 6 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, coronary artery bypass graft (CABG), congestive heart failure (CHF), cerebrovascular accident (CVA), transient ischemic Attack (TIA)
  • Uncontrolled hypertension defined by a SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg, with or without anti-hypertensive medication(s). Initiation or adjustment of antihypertensive medication(s) is allowed prior to study entry
  • Pre-existing condition (e.g., gastrointestinal tract disease), resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease that impairs the ability to swallow and retain dovitinib tablets.
  • Pre-existing thyroid abnormality with an inability to maintain thyroid function in the normal range with medication.
  • Patients with any of the following conditions:
  • Clinically significant pulmonary or GI bleeding of greater than 30 cc in the preceding 3 months
  • Serious or non-healing wound, ulcer, or bone fracture,
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment.
  • Patients with brain metastases.
  • Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol.
  • Any abnormal organ and marrow function as defined below:
  • Leukocytes <3,000/microL
  • Absolute neutrophil count <1,500/microL
  • Platelets <100,000/microL
  • Total bilirubin >1.5X institutional upper limit of normal (ULN)
  • AST(SGOT) / ALT(SGPT) >2.5X institutional ULN
  • Amylase/lipase outside normal institutional limits
  • Serum creatinine >1.5X ULN or Creatinine clearance <60mL/min/1.73 m2 for patients with creatinine levels above institutional normal
  • Pregnant or lactating women.
  • Women of child-bearing potential, who are biologically able to conceive, not employing two forms of highly effective contraception.
  • Note: Highly effective contraception (e.g. male condom with spermicide, diaphragm with spermicide, intra-uterine device) must be used by both sexes (female patients and their male partners) during the study and 30 days after the end of study treatment. Contraceptives that are affected by cytochrome P450 interactions (e.g. oral, implantable, injectable, or intrauterine hormonal contraceptives) are not considered effective for this study. Women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test ≤ 14 days prior to starting study drug.
  • Fertile males not willing to use contraception. Note: Fertile males must use condom with spermicide. Highly effective contraception (e.g. male condom with spermicide, diaphragm with spermicide, intra-uterine device) must be used by both sexes (male patients and their female partners) during the study and 30 days after the end of study treatment.
  • Psychiatric illness/social situations that would limit compliance with study requirements.
  • Receiving any other investigational agent(s).
  • Patients unwilling or unable to comply with the protocol.
  • Inability to understand or unable to provide written informed consent.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Canada5 sites

  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N 4N2

  • Northeast Cancer Centre, Health Sciences North

    Greater Sudbury, Ontario, P3E 5J1

  • Juravinski Cancer Centre

    Hamilton, Ontario, L8V 5C2

  • Ottawa General Hospital Cancer Centre

    Ottawa, Ontario, K1H 8L6

  • Princess Margaret Hospital

    Toronto, Ontario, M5G 1X6

Other trials in Canada

About this study

This is a single-arm, open label, two stage, phase II study of dovitinib in patients with advanced Malignant Pleural Mesothelioma (MPM). The primary purpose of this study is to evaluate the potential efficacy of dovitinib in the second- or third-line treatment of MPM using progression free survival (PFS).

Being tested
Dovitinib

What participants receive

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

  • DovitinibDrug

    Also called TKI258, RTK Inhibitor

    Treatment continued until Disease Progression, Toxicity, or patient withdrawal.

Study groups in NCT01769547
Study groupRoleWhat they receive
DovitinibExperimentalDovitinib 500 mg PO OD (5 days on, 2 days off); Each cycle = 28 days
Receives: Drug: Dovitinib

What is being measured

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

  1. Progression Free Survival (PFS)

    Measured: PFS measured from the time from the first date of treatment with dovitinib until the date of disease progression or date of death or last contact. Assessments every 8 weeks for disease progression for up to 2.5 years.

Secondary outcomes (6)

  1. Objective Response Rate (ORR)

    ORR using the modified RECIST criteria for MPM. This is defined as the number of patients with a complete or partial response divided by the number of patients who receive at least one dose of dovitinib.

    Measured: Response measured from the time from the first date of treatment with dovitinib. Patients should be re-evaluated for response every 8 weeks for up to 2.5 years

  2. Stable disease rate/disease control rate (ORR + SD)

    ORR + SD is defined as the number of patients with an objective response or stable disease using the modified RECIST criteria for MPM, divided by the number of patients who receive at least one dose of dovitinib

    Measured: Stable disease measured from the time from the first date of treatment with dovitinib until the criteria for disease progression are met. Assessments every 8 weeks for disease progression for up to 2.5 years

  3. Duration of response / stable disease

    The duration of overall CR measured from the time measurement criteria are first met for CR until the first date that recurrent disease is objectively documented.

    Measured: Duration of overall response measured from the time measurement criteria are met for CR or PR until the first date that recurrent or progressive disease is objectively documented. Assessments every 8 weeks for disease progression for up to 2.5 years.

  4. Overall survival (OS)

    Measured: OS measured from the time from the first date of treatment with dovitinib to the date of death or last contact. Patients will be followed up for survival for up to 1 year after disease progression.

  5. Biomarker assessments using tissue and plasma samples, and imaging.

    Biomarkers analysis will include analysis of archival tissue and plasma sample (wherever safely possible). In addition, pharmacodynamic effects will be measured by diffusion weighted MRI.

    Measured: Archival tissue sample at Baseline; Plasma samples at Baseline, Cycle 1 Week 2, Cycle 2 Week 1, Cycle 3 Week 1; Chest MRI at Baseline and Day 15.

  6. Safety and tolerability

    All patients will be evaluated for toxicity. Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest.

    Measured: From the time from the first date of treatment with dovitinib to the date the patient completes the study; patients will be followed up for survival for up to 1 year after disease progression.

Timeline

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

  1. First posted16 Jan 2013 (estimated)
  2. Study startMar 2013
  3. Primary completionJun 2015
  4. Study completionJun 2015

Why it stopped: Stage 1 accrual completed. Study did not proceed to Stage 2 accrual.

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
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01769547
Sponsor's protocol ID
OCOG-2012-DOVE-M
Acronym
DOVE-M
Status last verified
Sep 2015
First submitted
9 Jan 2013
Last updated
17 Sep 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • Laurie SA, Hao D, Leighl NB, Goffin J, Khomani A, Gupta A, Addison CL, Bane A, Seely J, Filion ML, Pond GR, Levine MN. A phase II trial of dovitinib in previously-treated advanced pleural mesothelioma: The Ontario Clinical Oncology Group. Lung Cancer. 2017 Feb;104:65-69. doi: 10.1016/j.lungcan.2016.12.004. Epub 2016 Dec 15.

    PubMed 28213002

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dovitinib in people with Advanced Malignant Pleural Mesothelioma and MPM, run by Ontario Clinical Oncology Group (OCOG) at 5 sites in Canada.

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 3 inclusion and 48 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: stopped early, as of the sponsor's last update on 17 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Canada. 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?

The study was stopped early (reason given: Stage 1 accrual completed. Study did not proceed to Stage 2 accrual.). Results are not available in the source record.

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?

Progression Free Survival (PFS) (time frame: PFS measured from the time from the first date of treatment with dovitinib until the date of disease progression or date of death or last contact. Assessments every 8 weeks for disease progression for up to 2.5 years.). 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 NCT01769547, 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 17 Sep 2015.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in