Dose Escalating Study of the Safety and Efficacy of Patup... | NCT00171834

NCT00171834

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Name	Type	Description	Arm Group Labels	Other Names
Patupilone	Drug	Patupilone (2.5 mg/mL) was supplied as a clear, colorless concentrate for solution for infusion in glass vials containing 5 mg/2 mL in Phase I and 10 mg/4 mL in Phase II part of the study. Patupilone was administered as a single intravenous (i.v.) infusion over 5 to 10 minutes (Amendment 1) till Amendment 2 and over 10 to 20 minutes (Amendment 2) till the completion of Phase I part of the study. Patupilone was administered as a single i.v. infusion over 20 minutes (Amendment 4), once every 3 weeks in Phase II part of the study.		EPO906 Epothilone B

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Phase I: Number of Total Dose-limiting Toxicity (DLT) During Dose Escalation to Determine Maximum Tolerated Dose (MTD)	The MTD was defined as the highest dose of patupilone administered every three weeks (q3w) where not more than one out of six patients experienced a DLT using a standard 3+3 design. Dose escalation started at 6.5 mg/m^2 until MTD in steps of 0.5 mg/m^2 until 12 mg/m^2, then in steps of 1 mg/m^2 till 13.0 mg/m^2. DLTs were assessed during cycle 1. During this time frame, no more than one DLT occurred in any of the explored dose levels up to 13 mg/m^2, thus, the MTD as defined by the protocol was not reached in this study.	Cycle 1 (21 days)
Phase II: Number of Participants With Best Overall Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST)	Overall response is the number of participants who had a complete response (CR) or a partial response (PR) based on local investigator's assessment of RECIST criteria. Per RECIST: CR, all detectable tumor has disappeared; PR, a >=30% decrease in the sum of the longest dimensions of the target lesions (TLs) taking as a reference the baseline sum, no worsening of non-TLs, and no new lesions; Progressive disease (PD), a >=20% increase in TLs, clearly worsening of non-TLs, or emergence of new lesions; Stable Disease (SD), small changes that do not meet previously given criteria.	At baseline, then every second cycle (approximately every 6 weeks), until disease progression or discontinuation. Average 18 weeks.

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Best Overall Response-Phase I	This was defined as the number of participants whose best overall response was CR or PR by RECIST. Per RECIST: CR, all detectable tumor has disappeared; PR, a >=30% decrease in the sum of the longest dimensions of the target lesions (TLs) taking as a reference the baseline sum, no worsening of non-TLs, and no new lesions; Progressive disease (PD), a >=20% increase in TLs, clearly worsening of non-TLs, or emergence of new lesions; Stable Disease (SD), small changes that do not meet previously given criteria.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients with histologic or cytologic confirmation of unresectable locally advanced or metastatic NSCLC (stage IIIB with pleural effusion only / stage IV) documented before first line therapy.
Prior treatment with a platinum-containing regimen
Age ≥18 years.
Performance status of 0-1 on the WHO scale.
Life expectancy of ≥3 months.
NSCLC patients should have at least one measurable lesion as defined by modified RECIST criteria. If the patient has had previous radiation to the marker lesion(s), the lesion must have demonstrated progression since the radiation.
NSCLC patients with controlled brain metastases are eligible to be enrolled in the brain metastases cohort at the MTD. "Controlled brain metastases" patients are defined as patients who are neurologically stable, i.e. have not experienced an increase in dose of steroidal or anticonvulsive therapy for at least 14 days prior to study entry.
Patients with brain metastases must be verified to have metastases secondary to NSCLC based on histology of primary and by temporal sequence of events (note: these patients are eligible even if lung disease is quiescent).
Patients with brain metastases must show evidence of residual disease or progression of disease since prior radiological or surgical therapy.
Patients with brain metastases should have at least one bidimensionally measurable intracranial lesion of minimum diameter 2 cm. Multifocal disease is permitted, but the eligibility of BM patients presenting with more than 6 intracranial lesions should be discussed with Novartis prior to enrolling the patient.
Patients with adequate hematologic parameters:
ANC ≥1.5 x 10^9/L;
Hb ≥9.0 g/dL,
Platelet count ≥100 x 10^9/L (untransfused).
Demonstrate the following blood chemistry laboratory values:
total bilirubin ≤ 1.5 x ULN;
AST/ALT ≤ 2.5 X ULN; (≤ 5 x ULN if hepatic metastasis is present)
alkaline phosphatase ≤ 2.5 x ULN; (≤ 5 x ULN if hepatic and/or bone metastasis are present)
serum creatinine < 2 x ULN.
Female patients must have a negative serum pregnancy test at screening. (Not applicable to patients with bilateral oophorectomy and/or hysterectomy or to those patients who are postmenopausal).
All patients of reproductive potential must agree to use an effective method of contraception during the study and three months following termination of treatment.
All patients must use a barrier method for contraception for sexual intercourse or avoid this for the first 5 days after patupilone infusion.
Written informed consent must be obtained.

Exclusion Criteria:

Patients who have received more than one prior chemotherapy regimen or any other systemic antineoplastic treatment including immunotherapy.
Patients who have received any investigational compound within the past 28 days or who are planning to receive other investigational drugs while participating in the study.
Patients with brain metastases who have received any prior chemotherapy regimen or any other systemic antineoplastic treatment for brain metastases.
Patients with brain metastases who have experienced a dose increase of 25% or more above previous dose, in concomitant steroidal or anticonvulsive therapy within 14 days prior to study entry.
Patients with brain metastases receiving steroidal or anticonvulsive therapy for whom a dose increase has been required within 14 days prior to start of study drug.
Patients with brain metastases who have leptomeningeal disease.
Patients with brain metastases who have extracranial metastases in more than two organs.
Patients with any peripheral polyneuropathy > Grade 1.
Patients with unresolved diarrhea > Grade 1.
Patients receiving hematopoietic growth factors except erythropoietin (refer Section 3.4.4).
Severe cardiac insufficiency (NYHA III or IV), with uncontrolled and/or unstable cardiac or coronary artery disease.
Patients taking warfarin or other agents containing warfarin, with the exception of low dose warfarin (1 mg or less daily) administered prophylactically for maintenance of in-dwelling lines or ports.
Patients who have not recovered fully from surgery for any cause, including brain metastases patients who have had a biopsy or surgical resection of the brain tumor within 2 weeks prior to starting study drug or who are not fully recovered from any prior biopsy or surgical resection.
Patients who have received radiation therapy or chemotherapy within the last four weeks. Palliative radiotherapy of metastasis in extremities is allowed but such lesions cannot be used as tumor markers.
Patients with the presence of active or suspected acute or chronic uncontrolled infection, including abscess or fistulae.
Patients known to be HIV positive.
History of another malignancy within 3 years prior to study entry, except curatively treated non-melanotic skin cancer or cervical cancer in situ.
For patients enrolling in the brain metastases cohort, any of the following exclusions to MRI imaging:

Cardiac pacemaker Ferromagnetic metal implants other than those approved as safe for use in MRI scanners Claustrophobia Obesity (exceeding the limits of scanning equipment)

Pregnant or lactating females.
A history of noncompliance to medical regimens or inability or unwillingness to return for all scheduled visits.

Other protocol-dependent inclusion / exclusion criteria may apply

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Norton Healthcare/Hospital Inc		Louisville	Kentucky	40232-5070	United States
Ellis Fisher Cancer Center

Arm/Group Information

ID	Title	Description
FG000	Patupilone ≤7.0 mg/m^2 (Phase I)	Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
FG001	Patupilone 7.5-8.0 mg/m^2 (Phase I)	Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
FG002	Patupilone 8.5-9.5 mg/m^2 (Phase I)	Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
FG003	Patupilone 10.0-11.5 mg/m^2 (Phase I)	Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
FG004	Patupilone 12.0-13.0 mg/m^2 (Phase I)	Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
FG005	Patupilone 10 mg/m^2 (Phase II) NSCLC Cohort	Patupilone was administered as a single i.v. infusion over 20 minutes (Amendment 4), once every 3 weeks.
FG006	Patupilone 10 mg/m^2 (Phase II) NSCLC w.BM Cohort	Patupilone was administered as a single i.v. infusion over 20 minutes (Amendment 4), once every 3 weeks.

ID	Title	Description
BG000	Patupilone ≤7.0 mg/m^2 (Phase I)	Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
BG001	Patupilone 7.5-8.0 mg/m^2 (Phase I)

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Secondary

Number of Participants With Best Overall Response-Phase I

This was defined as the number of participants whose best overall response was CR or PR by RECIST. Per RECIST: CR, all detectable tumor has disappeared; PR, a >=30% decrease in the sum of the longest dimensions of the target lesions (TLs) taking as a reference the baseline sum, no worsening of non-TLs, and no new lesions; Progressive disease (PD), a >=20% increase in TLs, clearly worsening of non-TLs, or emergence of new lesions; Stable Disease (SD), small changes that do not meet previously given criteria.

Full Analysis Set (FAS) consisted of all patients who received at least one dose of patupilone. Analysis of the primary and all secondary efficacy endpoints was performed based on this population. According to the Intention to Treat (ITT) principle, patients were analyzed based on the treatment to which they were assigned at study entry.

Posted

Number

Participants

Best achieved overall response according to RECIST from start of study until study discontinuation. Imaging was assessed every second cycle (ie. approximately every 6 weeks) until disease progression or discontinuation. Average 18 weeks

ID	Term
D002289	Carcinoma, Non-Small-Cell Lung
D001932	Brain Neoplasms
D008175	Lung Neoplasms

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms

OG000	Patupilone ≤7.0 mg/m^2 (Phase I)	Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
OG001	Patupilone 7.5-8.0 mg/m^2 (Phase I)	Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
OG002	Patupilone 8.5-9.5 mg/m^2 (Phase I)	Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
OG003	Patupilone 10.0-11.5 mg/m^2 (Phase I)	Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
OG004	Patupilone 12.0-13.0 mg/m^2 (Phase I)	Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.