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

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.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: CP-4126; Drug: Gemcitabine

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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • Institute Jules Bordet
• Netherlands
  • Amsterdam, Netherlands
    • The Netherlands Cancer Institute
  • Utrecht, Netherlands
    • University Medical Centre Utrecht

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. Symptomatic brain metastases
2. Current peripheral neuropathy of grade > 1 according to the National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0

3. 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
4. Mucositis of the upper digestive tract, including stomatitis
5. Participation in another therapeutic clinical study within 30 days of enrolment or during this clinical study
6. 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)]
7. Requirement of concomitant treatment with a non-permitted medication including alternative drugs and high doses of vitamins
8. History of allergic reactions to gemcitabine
9. Presence of any serious concomitant systemic disorders incompatible with the clinical study (e.g. uncontrolled inter-current illness including ongoing or active infection)
10. Presence of any significant central nervous system or psychiatric disorder(s) that would hamper the patient's compliance
11. Pregnant or breast feeding women
12. 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
13. Known positive status for HIV and/or hepatitis B or C
14. Any reason why, in the investigator's opinion, the patient should not participate
15. Condition that impairs ability to swallow pills
16. Coeliac disease or any other lipid malabsorption syndrome
17. Drug and/or alcohol abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; 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
EXPERIMENTAL: 2; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Step 1: MTD of oral CP-4126 in patients with advanced solid tumours, followed by establishing the recommended dose	6 months
Step 2: Pharmacokinetic parameters comparison of oral CP-4126 with IV gemcitabine	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Tolerability of oral CP-4126	12 months
Biovailability of oral CP-4126	12 months
Preliminary assessment of antitumor activity of oral CP-4126	18 months

Collaborators and Investigators

• Sponsor: Clavis Pharma
• Investigators: Principal Investigator: Ahmad H Awada, MD, Institute Jules Bordet

Publications and helpful links

General Publications

• Stuurman FE, Voest EE, Awada A, Witteveen PO, Bergeland T, Hals PA, Rasch W, Schellens JH, Hendlisz A. Phase I study of oral CP-4126, a gemcitabine derivative, in patients with advanced solid tumors. Invest New Drugs. 2013 Aug;31(4):959-66. doi: 10.1007/s10637-013-9925-z. Epub 2013 Jan 24.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (ACTUAL): April 1, 2010
• Study Completion (ACTUAL): April 1, 2010

Study Registration Dates

• First Submitted: October 22, 2008
• First Submitted That Met QC Criteria: October 22, 2008
• First Posted (ESTIMATE): October 23, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): September 6, 2010
• Last Update Submitted That Met QC Criteria: September 3, 2010
• Last Verified: September 1, 2010

More Information

Terms related to this study

• Keywords: Cancer; Gemzar; Metastatic; Solid tumours; CP-4126; Gemzitabine
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine
• Other Study ID Numbers: CP4126-111