Phase II study of PHA-739358 administered by a 24-hour IV infusion every 14 days in advanced/metastatic breast, ovarian, colorectal, pancreatic, small cell lung and non small cell lung cancers. - not available

Phase 1

• Conditions: Advanced/metastatic breast, ovarian, colorectal, pancreatic, small cell lung, non small cell lung and squamous non small cell lung cancers.; MedDRA version: 13.1Level: PTClassification code 10057529Term: Ovarian cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 13.1Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 13.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 13.1Level: PTClassification code 10052358Term: Colorectal cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 13.1Level: PTClassification code 10059514Term: Small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 13.1Level: PTClassification code 10033610Term: Pancreatic carcinoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2006-003772-35-GB
• Lead Sponsor: erviano Medical Sciences S.r.l.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-03-09
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 224

Inclusion Criteria

1. Patients with histologically or cytologically documented progressive advanced/metastatic disease in one of the following solid tumors (see below):
· Breast cancer (3rd line of chemotherapy),
· Ovarian cancer (3rd line, platinum resistant/refractory disease),
· Colorectal cancer (3rd line),
· Pancreatic Cancer (2nd line),
· Small Cell Lung Cancer (2nd line),
· Non Small Cell Lung Cancer (2nd line),
. Squamous Non Small Cell Lung Cancer (2nd line).

Note: Any adjuvant chemotherapy followed by the recurrence of the disease within 12 months after the start of the adjuvant treatment will be considered as one chemotherapy line for advanced/metastatic disease.
Platinum Resistant: Disease that relapsed within 6 months after completing prior platinum therapy.
Platinum Refractory: Disease that progressed or was stable during prior platinum therapy.

2. Prior chemotherapy must have been completed 2 weeks before study entry.

3. Available information on the first day of administration of the previous chemotherapy and the precise date when progression has been assessed.

4. Prior radiotherapy is allowed provided that a minimum of 2 weeks has elapsed between the end of prior radiotherapy and the entry into the trial.

5. Age 18 years or older.

6. ECOG performance status 0 – 1.

7. Life expectancy of at least 3 months.

8. Hematological and biochemical parameters:
· Bilirubin =1,5 UNL,
· AST/ALT = 2,5 UNL (= 5 UNL in case of liver metastases),
· ALP = 2,5 UNL (= 5 UNL in case of liver and/or bone metastases),
· Creatinine within normal limits (if out of range then perform the Creatinine clearance evaluation = 50 ml/min),
· ANC = 1,500 cells/mm3,
· Platelets count = 75,000 cells/mm3,
· Hemoglobin = 10 g/dl.

9. All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to NCI CTCAE version 3.0 grade = 1.

10. Personally signed and dated IEC/IRB-approved informed consent form.

11. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Previous high-dose chemotherapy requiring bone marrow rescue.

2. Concurrent enrollment in another investigational drug trial within the last 4 weeks.

3. Known brain or leptomeningeal disease (baseline computerized tomography [CT] or MRI scan of the brain required only in case of clinical suspicion of central nervous system metastases).

4. Uncontrolled hypertension with blood pressure exceeding 160/100 mmHg.

5. Pregnancy or breast-feeding. Female patients must agree to avoid becoming pregnant during the study and in the following 3 months after the end of the treatment, be surgically sterile or be postmenopausal. Male patients must agree to have no intention to father a child during the study and in the following 3 months after the end of the treatment.

6. Abnormal LVEF < 40% by Echocardiography or MUGA <45%.

7. Any of the following in the past 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis or other significant thromboembolic event.

8. Cardiac dysrhythmias grade = 2 according to NCI CTCAE version 3.0.

9. Known active infection including known human immunodeficiency virus (HIV) positivity.

10. Other severe acute or 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 patient inappropriate for entry into this study.

11. History of previous cancer, except skin basal-cell carcinoma or in situ carcinoma of the cervix, within the previous 5 years.

12. Marked baseline prolongation of QT/QTc interval [(e.g., repeated demonstration of a QTc interval > 45 milliseconds (ms)].

13. A history of additional risk factors for torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).

14. Use of concomitant medications that prolong the QT/QTc interval.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine if PHA-739358 has an antitumor activity against breast, ovarian, pancreatic, colorectal, small and non-small cell lung cancers.;Secondary Objective: ·To evaluate the antitumor activity of PHA-739358 in comparison to the last prior therapy,<br>·To evaluate the safety profile of PHA-739358,<br>·To monitor the PK of PHA-739358 in plasma, <br>·To analyze genes/proteins which might predict responsiveness to Aurora kinase inhibitors in tumor biopsies collected at diagnosis and/or thereafter from ovarian cancer patients,<br>.To analyze genes/proteins which might predict responsiveness to PHA-739358 in paraffin embedded tumor biopsies collected at diagnosis and/or thereafter, in any case before the enrollment in the study, from NSCLC patients with squamous cell histology.<br>;Primary end point(s): Progression Free Rate at 4 months of treatment.