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

NCT01769547 | Terminated Phase 2 DMC

• 1 other identifier: OCOG-2012-DOVE-M
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 5

Brief 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).

Conditions

Advanced Malignant Pleural Mesothelioma; MPM

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  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)

• Objective Response Rate (ORR)

  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

• Stable disease rate/disease control rate (ORR + SD)

  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

• Duration of response / stable disease

  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.

• Overall survival (OS)

  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.

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

  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.

Study Arms (1)

Dovitinib

EXPERIMENTAL

Dovitinib 500 mg PO OD (5 days on, 2 days off); Each cycle = 28 days

Drug: Dovitinib

Interventions

Dovitinib DRUG

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

Also known as: TKI258, RTK Inhibitor

Dovitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Ontario Clinical Oncology Group (OCOG): lead
• Novartis Pharmaceuticals: collaborator

Study Sites (5)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Northeast Cancer Centre, Health Sciences North

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

Ottawa General Hospital Cancer Centre

Ottawa, Ontario, K1H 8L6, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 1X6, Canada

Location

Related Publications (1)

• 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.

  PMID: 28213002 DERIVED

MeSH Terms

Interventions

4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one

Study Officials

• Scott Laurie, MD

  Ottawa General Hospital Cancer Centre

  PRINCIPAL INVESTIGATOR

• Mark Levine, MD

  Ontario Clinical Oncology Group (OCOG)

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2013
• First Posted: January 16, 2013
• Study Start: March 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: September 17, 2015

Record last verified: 2015-09

Locations

CA (5)