Ganetespib With Pemetrexed-cisplatin, in Patients With Malignant Pleural Mesothelioma (MESO-02)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by University College, London
Sponsor:
Collaborator:
Cancer Research UK
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT01590160
First received: April 30, 2012
Last updated: September 4, 2013
Last verified: September 2013
  Purpose

Malignant pleural mesothelioma (MPM) is a rapidly lethal cancer arising from the parietal pleural mesothelium, and is associated with exposure to asbestos.

Once a rare disease, it is increasing in incidence in the UK and is presently more common than cervical cancer. MPM is characterized by local invasion of adjacent structures including the chest wall, mediastinum, diaphragm and pericardium resulting in progressive shortness of breath.

Median survival with best supportive care alone is approximately 6-9 months and most cases of mesothelioma present in the advanced setting. Therefore this trial will be looking at whether a new drug, Ganetespib has any improvement on survival for these types of patients.


Condition Intervention Phase
Lung Cancer - Malignant Pleural Mesothelioma
Drug: Ganetespib
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of First Line Ganetespib With Pemetrexed-cisplatin, in Patients With Malignant Pleural Mesothelioma

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • Maximum Tolerated Dose of Ganetespib [ Time Frame: 6 Months ] [ Designated as safety issue: Yes ]

    Primary endpoint (phase I): Dose-limiting toxicities during Cycles 1 & 2; and number of cycles of pemetrexed-cisplatin given.

    The Phase I trial will consist of three ganetespib dose cohorts, each with 3 or 6 patients:

    • Cohort 1: 100mg/m2 IV on day 1 and day 15 of each cycle
    • Cohort 2: 150mg/m2 IV on day 1 and day 15 of each cycle
    • Cohort 3: 200mg/m2 IV on day 1 and day 15 of each cycle

    Primary endpoint (phase II): Progression free survival



Secondary Outcome Measures:
  • Progression Free Survival [ Time Frame: 24 Months ] [ Designated as safety issue: Yes ]

    Secondary endpoints (phase I):

    • To examine the number of cycles of pemetrexed/cisplatin/(cisplatin) chemotherapy administered.
    • To examine the objective tumour response according to meso-modified RECIST, and the overall response rate.

    Secondary endpoints (phase II):

    • To examine the frequency of all Adverse Events graded by NCI-CTCAE version 4, in particular those with grade 3 or 4 events.
    • To examine the objective tumour response according to meso-modified RECIST, and the overall response rate.
    • To examine overall survival.


Estimated Enrollment: 24
Study Start Date: August 2013
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cisplatin/Pemetrexed
Cisplatin 75mg/m2, Day 1 every 21 days Pemetrexed 500mg/m2, Day 1 every 21 days
Drug: Ganetespib
IV, Using dose from Phase I
Experimental: Cis/Pem
Cisplatin 75mg/m2, Day 1 every 21 days Pemetrexed 500mg/m2, Day 1 every 21 days
Drug: Placebo
Matched Placebo, administered IV

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Pathological confirmation of malignant pleural mesothelioma
  2. Measurable disease using meso-modified RECIST criteria (This scan must be within 28 days of registration/randomization)
  3. Performance status ECOG 0-1
  4. Age at least 18 years
  5. Adequate haematological status:

    • Haemoglobin 100g/L or greater
    • Neutrophil count ≥1.5 x 109/L
    • Platelets ≥100 x 109 /L
  6. Adequate organ function:

    1. Bilirubin ≤1.5x ULN, ALP ≤2.5x ULN, ALT or AST ≤1.5x ULN
    2. Serum creatinine ≤1.5 x ULN or calculated creatinine ≥ 50ml/min (C&G or EDTA) (appendix 4)
  7. Negative serum pregnancy test for female patients within 1 week prior to starting the first dose ganetespib.
  8. Male subjects and women of child bearing potential must agree to use an acceptable method of birth control for the duration of the trial and for 6 months after the last trial treatment cycle has finished. (See section 5.3.3 for details)
  9. Ability to understand and willing to sign the written informed consent to participate (including donation of diagnostic biopsy tissue for research)
  10. Ability to comply with the requirements of the protocol

Exclusion Criteria:

  1. Prior exposure to other investigational or commercial agents or therapies administered with the intent of treating the patient's malignancy. This includes crizotinib, other ALK-targeted agents, and any Hsp90 inhibitor (e.g. ganetespib). Prior valproic acid is acceptable but only if there has been at least 30 days wash-out period
  2. Evidence of CNS metastases that in the opinion of the investigator should receive local treatment prior to systemic cytotoxic chemotherapy
  3. Uncontrolled intercurrent illness including but not limited to:

    • Symptomatic neurological illness
    • Active uncontrolled systemic infection considered opportunistic, life threatening or clinically significant at the time of treatment
    • Significant pulmonary disease or hypoxia
    • Psychiatric illness/social situations that would limit compliance with trial requirements
    • Human immunodeficiency virus (HIV)-positive patients
    • Known hepatitis B or C infection
    • Uncontrolled diabetes mellitus
  4. Known serious cardiac illness including but not confined to:

    • Uncontrolled congestive heart failure (CHF), New York Heart Association class II/III/IV, with a history of dyspnoea, orthopnea or edemathat requires current treatment with angiotensin converting enzyme inhibitors,angiotensin II receptor blockers, beta-blockers or diuretics. NOTE: Use of these medications for the treatment of hypertension is allowed.
    • Baseline QTc > 470 msec or history of QT prolongation while taking other medications
    • Left ventricular ejection fraction (LVEF) < 45 %
    • High-risk uncontrolled arrhythmias (e.g., ventricular arrhythmias, high-grade atrioventricular (AV)-block, supra-ventricular arrhythmias which are not adequately rate-controlled)
    • Arrhythmias that require current treatment with the following anti-arrhythmic drugs: flecainide, moricizine or propafenone
    • A myocardial infarction within the last 6 months or unstable angina
  5. The patient has a history of prior malignant tumour, unless the patient has been without evidence of disease for at least three years, or the tumour was a non-melanoma skin tumour or in-situ cervix carcinoma
  6. Pregnant women or those who are lactating
  7. Preplanned surgery or procedures that would interfere with the conduct of the trial
  8. Patients who have had surgery (does not include pleurodesis or pleurectomy) within 28 days of randomization should not be included
  9. Receipt of extensive radiation therapy, systemic chemotherapy, or other anti-neoplastic therapy within 4 weeks before enrollment is not allowed. However, drain site radiotherapy is allowed
  10. Significant weight loss (≥10% body weight) within the 4 weeks prior to Cycle 1 Day 1.
  11. Patients who have had a yellow fever vaccination in the previous 30 days.
  12. Other medications, severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01590160

Contacts
Contact: Professor D Fennell, PhD FRCP 0116 252 5174 df132@leicester.ac.uk

Locations
United Kingdom
UCL Cancer Trials Centre Recruiting
London, United Kingdom, W1T 4TJ
Contact: Lynda Micklewright    02076799105    l.micklewright@ucl.ac.uk   
Principal Investigator: Professor Dean Fennell, PhD FRCP         
Sponsors and Collaborators
University College, London
Cancer Research UK
Investigators
Study Chair: Professor D Fennell, MBBS University of Leicester & Leicester University Hospitals
  More Information

No publications provided

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01590160     History of Changes
Other Study ID Numbers: UCL/12/0158, CMS # 1995, A15183, 2012-001598-10, TBC
Study First Received: April 30, 2012
Last Updated: September 4, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Lung Neoplasms
Mesothelioma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Mesothelial
Pemetrexed
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on July 28, 2014