A Phase I Clinical Study of Oral CP-4126 in Patients With Advanced Solid Tumour - Full Text View

Sponsored by:	Clavis Pharma
Information provided by:	Clavis Pharma
ClinicalTrials.gov Identifier:	NCT00778128

Purpose

At step 1, patients with advanced solid tumors will receive CP-4126 capsules following a dose escalation schedule until the maximum tolerated dose is reached. At step 2, 20 patients will be randomized. They will receive at days 1 and 8 in a double cross design either oral CP-4126 at the recommended dose or gemcitabine 1000mg/m2 intravenously. At both steps, the schedule of treatment will be day 1, 8, 15 q4w until complete response or disease worsening/ progressing. All further treatment at step 2 will be oral CP-4126.

Condition	Intervention	Phase
Solid Tumors	Drug: CP-4126 Drug: Gemcitabine	Phase I

MedlinePlus related topics: Cancer

Drug Information available for: Gemcitabine hydrochloride Gemcitabine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase I Clinical Study of Oral CP-4126 in Patients With Advanced Solid Tumour

Further study details as provided by Clavis Pharma:

Primary Outcome Measures:

Step 1: MTD of oral CP-4126 in patients with advanced solid tumours, followed by establishing the recommended dose [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Step 2: Pharmacokinetic parameters comparison of oral CP-4126 with IV gemcitabine [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Tolerability of oral CP-4126 [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Biovailability of oral CP-4126 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Preliminary assessment of antitumor activity of oral CP-4126 [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	35
Study Start Date:	October 2008
Estimated Study Completion Date:	June 2010
Estimated Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Step 1: Dose escalation - oral CP-4126 Step 2: Oral CP-4126 on day 1 and 15 in a 4 week schedule. One dose (only) gemcitabine IV on day 8.	Drug: CP-4126 Step 1: Dose escalation oral CP-4126 until maximum tolerated dose. Step 2: Oral CP-4126 day 1 and 15 + IV Gemcitabine 1000 mg/m2 day 8 in a 4 week schedule until complete response or disease worsening / progression Drug: Gemcitabine Step 1: Dose escalation oral CP-4126 until maximum tolerated dose Step 2: Oral CP-4126 day 8 and 15 + IV Gemcitabine 1000 mg/m2 day 1 in a 4 week schedule until complete response or disease worsening / progression
2: Experimental Step 1: Dose escalation - oral CP-4126 Step 2: Oral CP-4126 on day 8 and 15 in a 4 week schedule. One dose (only) gemcitabine IV on day 1.	Drug: CP-4126 Step 1: Dose escalation oral CP-4126 until maximum tolerated dose. Step 2: Oral CP-4126 day 1 and 15 + IV Gemcitabine 1000 mg/m2 day 8 in a 4 week schedule until complete response or disease worsening / progression Drug: Gemcitabine Step 1: Dose escalation oral CP-4126 until maximum tolerated dose Step 2: Oral CP-4126 day 8 and 15 + IV Gemcitabine 1000 mg/m2 day 1 in a 4 week schedule until complete response or disease worsening / progression

Arms

Assigned Interventions

1: Experimental

Step 1: Dose escalation - oral CP-4126

Step 2: Oral CP-4126 on day 1 and 15 in a 4 week schedule. One dose (only) gemcitabine IV on day 8.

Drug: CP-4126

Step 1: Dose escalation oral CP-4126 until maximum tolerated dose. Step 2: Oral CP-4126 day 1 and 15 + IV Gemcitabine 1000 mg/m2 day 8 in a 4 week schedule until complete response or disease worsening / progression

Drug: Gemcitabine

Step 1: Dose escalation oral CP-4126 until maximum tolerated dose Step 2: Oral CP-4126 day 8 and 15 + IV Gemcitabine 1000 mg/m2 day 1 in a 4 week schedule until complete response or disease worsening / progression

2: Experimental

Step 1: Dose escalation - oral CP-4126

Step 2: Oral CP-4126 on day 8 and 15 in a 4 week schedule. One dose (only) gemcitabine IV on day 1.

Drug: CP-4126

Step 1: Dose escalation oral CP-4126 until maximum tolerated dose. Step 2: Oral CP-4126 day 1 and 15 + IV Gemcitabine 1000 mg/m2 day 8 in a 4 week schedule until complete response or disease worsening / progression

Drug: Gemcitabine

Step 1: Dose escalation oral CP-4126 until maximum tolerated dose Step 2: Oral CP-4126 day 8 and 15 + IV Gemcitabine 1000 mg/m2 day 1 in a 4 week schedule until complete response or disease worsening / progression

Detailed Description:

This is a multicentre clinical study conducted in Belgium and in The Netherlands. The study is a phase I divided in 2 steps: The first step is a dose escalation to define the RD. At the second step the PK profile of oral CP-4126 will be compared with the PK profile of IV gemcitabine. In addition, the study is conducted to characterize the tolerability of oral CP-4126, to evaluate its bioavailability, and to make a preliminary assessment of antitumor activity in patients with solid tumours.

Eligibility

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

Criteria

Inclusion Criteria:

Histologically or cytologically confirmed solid tumour diagnosis
Locally advanced or metastatic disease, for which there is no known effective treatment
Performance Status 0 - 2 according to ECOG (Eastern Cooperative Oncology Group) Performance Status
Age 18 years or more
Life expectancy > 3 months
Adequate hematological and biological functions:
Signed informed consent

Exclusion Criteria:

Symptomatic brain metastases
Current peripheral neuropathy of grade > 1 according to the National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
Radiotherapy
- to more than 30 % of bone marrow
- single dose up to 8 Gy
- less than one week prior to the study treatment
- of the upper GI tract
Mucositis of the upper digestive tract, including stomatitis
Participation in another therapeutic clinical study within 30 days of enrolment or during this clinical study
Previous anticancer therapy (chemotherapy, hormone therapy or immunotherapy) within 30 days prior to the first dose of oral CP-4126 [6 weeks for mitomycin C and BCNU (= carmustine) and CCNU (=lomustine)]
Requirement of concomitant treatment with a non-permitted medication including alternative drugs and high doses of vitamins
History of allergic reactions to gemcitabine
Presence of any serious concomitant systemic disorders incompatible with the clinical study (e.g. uncontrolled inter-current illness including ongoing or active infection)
Presence of any significant central nervous system or psychiatric disorder(s) that would hamper the patient's compliance
Pregnant or breast feeding women
Absence of adequate contraception for both male and female fertile patients for the duration of the study; and also for six months after last treatment
Known positive status for HIV and/or hepatitis B or C
Any reason why, in the investigator's opinion, the patient should not participate
Condition that impairs ability to swallow pills
Coeliac disease or any other lipid malabsorption syndrome
Drug and/or alcohol abuse

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00778128

Contacts

Contact: Ahmad H Awada, MD

+32 2 541 31 89

ahmad.awada@bordet.be

Locations

Belgium
Institute Jules Bordet	Recruiting
Brussels, Belgium, 1000
Contact: Ahmad H Awada, MD +32 2 541 31 89 ahmad.awada@bordet.be
Principal Investigator: Ahmad H Awada, MD
Netherlands
University Medical Centre Utrecht	Not yet recruiting
Utrecht, Netherlands
Contact: Emile Voest, MD +31 887 55 62 65 e.e.voest@umcutrecht.nl
Principal Investigator: Emile Voest, MD
The Netherlands Cancer Institute	Not yet recruiting
Amsterdam, Netherlands
Contact: Jan H M Schellens, MD +31 20 512 24 46 jhm@nki.nl
Principal Investigator: Jan H M Schellens, MD

Sponsors and Collaborators

Clavis Pharma

Investigators

Principal Investigator:

Ahmad H Awada, MD

Institute Jules Bordet

More Information

Responsible Party:	Clavis Pharma ASA ( Jean-Michel Gaullier )
Study ID Numbers:	CP4126-111
Study First Received:	October 22, 2008
Last Updated:	October 22, 2008
ClinicalTrials.gov Identifier:	NCT00778128
Health Authority:	Belgium: Federal Agency for Medicines and Health Products; The Netherlands: Centrale Commissie Mengsebonden Onderzoek, The Haag, Dutch Medicine Agency

Keywords provided by Clavis Pharma:

CP-4126
Cancer
Metastatic

Solid tumours
Gemzitabine
Gemzar

Study placed in the following topic categories:

Gemcitabine

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs

Enzyme Inhibitors
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on January 14, 2009