Clinical trial NCT00778128: A Phase I Clinical Study of Oral CP-4126 in Patients With Advanced Solid Tumour
Official title: A Phase I Clinical Study of Oral CP-4126 in Patients With Advanced Solid Tumour
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: CP-4126
Cancer
Metastatic
Solid tumours
Gemzitabine
Gemzar
Lead sponsor: Clavis Pharma
Sponsor class: INDUSTRY
First posted: 2008-10-23
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 criteria: 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

Primary outcomes:
measure: Step 1: MTD of oral CP-4126 in patients with advanced solid tumours, followed by establishing the recommended dose
timeFrame: 6 months
measure: Step 2: Pharmacokinetic parameters comparison of oral CP-4126 with IV gemcitabine
timeFrame: 12 months
Secondary outcomes:
measure: Tolerability of oral CP-4126
timeFrame: 12 months
measure: Biovailability of oral CP-4126
timeFrame: 12 months
measure: Preliminary assessment of antitumor activity of oral CP-4126
timeFrame: 18 months
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Institute Jules Bordet
city: Amsterdam
country: Netherlands
facility: The Netherlands Cancer Institute
city: Utrecht
country: Netherlands
facility: University Medical Centre Utrecht
Study officials:
affiliation: Institute Jules Bordet
name: Ahmad H Awada, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.