A Phase II Study of PF-03446962 in Patients With Advanced Malignant Pleural Mesothelioma

NCT01486368 | Completed Phase 2 DMC

• 1 other identifier: I207
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 7

Brief Summary

This is a non-randomized open label multicentre Phase II trial to evaluate the response rate of PF03446962 in patients with advanced malignant pleural mesothelioma who have been previously treated with cytotoxic chemotherapy.

Conditions

Malignant Pleural Mesothelioma

Outcome Measures

Primary Outcomes (1)

• Response Rate

  Assessing the efficacy (response rate, complete and partial) of PF-03446962 given by IV infusion Day 1 of a 2 week cycle(14 days = 1 cycle) in patients with malignant pleural mesothelioma and previously treated with cytotoxic therapy.

  30 months

Secondary Outcomes (3)

• Amount and severity of adverse events

  30 months

• Duration of Response

  30 months

• Blood and tissue marker evaluation

  30 months

Study Arms (1)

PF-03446962

EXPERIMENTAL

Drug: PF-03446962

Interventions

PF-03446962 DRUG

PF-03446962 will be administered by IV infusion every 2 weeks (q2w). A cycle will be 2 weeks in duration and include one administration of PF-03446962.

PF-03446962

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed malignant pleural mesothelioma.
• Patients must have advanced and/or metastatic disease, incurable by standard therapies.
• All patients must have a tumour block from their primary or metastatic tumour available and consent to release the block for correlative analyses. Centre/pathologist must have agreed to the submission of the specimens in both Stage I and II of accrual. For patients entered in Stage I of accrual, if no archival tissue is available, patient must undergo a biopsy prior to registration.
• All patients entered in Stage II of accrual must have an accessible tumour lesion (from primary or metastatic disease) for a fresh biopsy, which is formalin fixed and paraffin embedded. These patients must consent to this biopsy for entry on the trial.
• Presence of clinically and/or radiologically documented disease. At least one site of disease must be unidimensionally measurable as follows:
• Chest X-ray ≥ 20 mm CT scan (with slice thickness of ≤ 5 mm) ≥ 10 mm longest diameter Physical exam (using calipers) ≥ 10 mm Lymph nodes by CT scan ≥ 15 mm measured in short axis All radiology studies must be performed within 21 days prior to registration (Exception: Within 28 days if negative).
• Age ≥ 18 years.
• Patients must have a life expectancy of at least 12 weeks.
• Previous Therapy
• Cytotoxic Chemotherapy:
• Patients are eligible after first line cytotoxic chemotherapy has failed
• Patients must have received one, but no more than one, combination chemotherapy regimen for advanced disease, which must have contained a platinum agent, and treatment failure must have been documented
• o Exchange of one chemotherapy agent for another within a combination chemotherapy regimen due to toxicity (and not due to progressive disease) is not considered a new regimen in the following circumstances
• Carboplatin is substituted for cisplatin due to nephrotoxicity or ototoxicity
• One agent in the combination regimen is changed due to hypersensitivity occurring in the first cycle

You may not qualify if:

• Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥5 years.
• Patients with known brain metastases. (A head CT is not necessary to rule out brain metastases, unless there is clinical suspicion of CNS involvement). Patients with known brain metastases will be excluded from this trial due to their poor prognosis and their likelihood of developing progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to PF-03446962.
• Patients receiving concurrent treatment with other anti-cancer therapy or other investigational anticancer agents.
• Patients with any of the following cardiovascular findings are to be excluded:
• QTc prolongation ( defined as a mean QTc interval with Bazetts correction equal to or greater than 470 msec) in screening ECG or history of familial long QT syndrome. An ECG must be done within 14 days prior to registration.
• Patients with resting BP consistently higher than, systolic \> 150 mmHg and/or diastolic \> 100 mmHg (in the presence or absence of a stable dose of anti-hypertensive medication) or poorly controlled hypertension, history of labile hypertension or poor compliance with anti-hypertensive medication.
• Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial infarction within the previous year or cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects). Patients with a significant cardiac history even if controlled, should have a LVEF \> 50%.
• History of pulmonary embolism within the past 12 months; exceptions may be made for incidental pulmonary emboli found on routine scanning providing not within the past 6 months.
• History of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study entry.
• Patients with overt bleeding from any site (\> 30 ml bleeding/episode) within 3 months of study entry are not eligible. No clinically relevant hemoptysis (\> 5 ml fresh blood) within 4 weeks prior to study entry is permitted. Patients with only flecks of blood in sputum are permitted.
• Patients who require use of therapeutic doses of anticoagulants such as warfarin, heparin or low molecular weight heparin (except for low doses for prophylaxis). INR must be done within 7 days prior to registration.
• Patients with bowel obstruction or any condition or gastrointestinal tract disease that would increase the risk for gastrointestinal perforation, including abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment.
• Patients with serious illness or medical condition which would not permit the patient to be managed according to the protocol including, but not limited to:
• History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent or limit compliance with study requirements;

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead
• Pfizer: collaborator

Study Sites (7)

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, V3V 1Z2, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Ottawa Health Research Institute - General Division

Ottawa, Ontario, K1H 8L6, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

• Wheatley-Price P, Chu Q, Bonomi M, Seely J, Gupta A, Goss G, Hilton J, Feld R, Lee CW, Goffin JR, Maksymiuk A, Murray N, Hagerman L, Bradbury PA. A Phase II Study of PF-03446962 in Patients with Advanced Malignant Pleural Mesothelioma. CCTG Trial IND.207. J Thorac Oncol. 2016 Nov;11(11):2018-2021. doi: 10.1016/j.jtho.2016.06.024. Epub 2016 Jul 20.

  PMID: 27449804 RESULT

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

ascrinvacumab

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Quincy Chu

  Cross Cancer Institute, Edmonton, AB Canada

  STUDY CHAIR

• Paul Wheatley-Price

  Ottawa Health Research Institute - General Division, Ottawa ON Canada

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: December 1, 2011
• First Posted: December 6, 2011
• Study Start: June 26, 2012
• Primary Completion: April 27, 2014
• Study Completion: February 13, 2015
• Last Updated: August 4, 2023

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (7)