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A Phase I/II Study of First Line Ganetespib With Pemetrexed-cisplatin, in Patients With Malignant Pleural Mesothelioma

Phase 1/Phase 2
18 Years
Not Enrolling
Lung Cancer - Malignant Pleural Mesothelioma

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Trial Information

A Phase I/II Study of First Line Ganetespib With Pemetrexed-cisplatin, in Patients With Malignant Pleural Mesothelioma

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/randomisation)

3. Performance status ECOG 0-1

4. Age at least 18 years

5. Adequate haematological status:

- Haemoglobin 10g/dl 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

- 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 thesemedications for the
treatment of hypertension is allowed.

- Baseline QTc > 470 msec or history of QT prolongation while taking

- Left ventricular ejection fraction (LVEF) < 45 %

- High-risk uncontrolled arrhythmias (e.g., ventricular arrhythmias,
high-gradeatrioventricular (AV)-block, supra-ventricular arrhythmias which are
notadequately 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. Pre-planned 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 randomisation should not be included

9. Receipt of extensive radiation therapy, systemic chemotherapy, or other
anti-neoplastic therapy within 4 weeks before enrolment 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.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose of Ganetespib

Outcome Description:

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 8 of each cycle Cohort 2: 150mg/m2 IV on day 1 and day 8 of each cycle Cohort 3: 200mg/m2 IV on day 1 and day 8 of each cycle Primary endpoint (phase II): Progression free survival

Outcome Time Frame:

6 Months

Safety Issue:



United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:




Start Date:

September 2012

Completion Date:

Related Keywords:

  • Lung Cancer - Malignant Pleural Mesothelioma
  • Lung Neoplasms
  • Mesothelioma