Satraplatin and Vinorelbine in Advanced Solid Tumors

Sponsor

Southern Europe New Drug Organization (Other)

Overall Status

Unknown status

CT.gov ID

NCT01220284

Collaborator

Agennix (Industry), Pierre Fabre Laboratories (Industry)

Enrollment

Locations

Arm

Duration (Months)

13.5

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Vinorelbine (NVB) and platinum compounds are anticancer agents with broad spectrum of efficacy, clinically and preclinically proven synergism and only partially overlapping toxicities. Combinations with vinorelbine and platinum compounds with limited neurotoxicity are among the most used palliative regimens in a variety of solid tumors, including NSCLC, breast and cervical cancer. The oral platinum analogue satraplatin (SATRA) has been brought into clinical development because of the antitumor activity and toxicity comparable to those of carboplatin, together with a good acceptability of the oral administration.The recent availability of oral formulation of anticancer agents of proven efficacy in some indications is likely to become a valid option which could affect clinical daily management. The oral administration of vinorelbine and satraplatin might represent a reasonable option of palliative treatment in patients with advanced breast cancer, NSCL, GU or GY tumors for which a curative treatment can not be provided.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Drug: Satraplatin in combo with vinorelbine	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

27 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Dose-finding Study of Satraplatin in Combination With Oral Vinorelbine in Patients With Advanced Solid Tumors

Study Start Date :

Feb 1, 2008

Anticipated Primary Completion Date :

Nov 1, 2010

Anticipated Study Completion Date :

Feb 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Satraplatin in combo with vinorelbine Escalating doses of satraplatin and oral vinorelbine in subsequent cohorts of 3-6 patients according to the type and severity grade of acute toxicities observed during cycle 1. The dose escalation process will be discontinued once the MTD is achieved.	Drug: Satraplatin in combo with vinorelbine Satraplatin (gelatin capsules) p.o. on days 1 to 5 (from 60 mg/m2 up to 80 mg/m2) Vinorelbine (soft capsules) p.o. on days 1, 8 and 15 (from 60 mg/m2 up to 80 mg/m2) The treatment is repeated every 4 weeks. Other Names: - Satraplatin (codenamed JM216) - Vinorelbine, Navelbine

Arm

Intervention/Treatment

Experimental: Satraplatin in combo with vinorelbine

Escalating doses of satraplatin and oral vinorelbine in subsequent cohorts of 3-6 patients according to the type and severity grade of acute toxicities observed during cycle 1. The dose escalation process will be discontinued once the MTD is achieved.

Drug: Satraplatin in combo with vinorelbine

Satraplatin (gelatin capsules) p.o. on days 1 to 5 (from 60 mg/m2 up to 80 mg/m2) Vinorelbine (soft capsules) p.o. on days 1, 8 and 15 (from 60 mg/m2 up to 80 mg/m2) The treatment is repeated every 4 weeks.

Other Names:

- Satraplatin (codenamed JM216)

- Vinorelbine, Navelbine

Outcome Measures

Primary Outcome Measures

Maximum Tolerated Dose (MTD) based upon study drug related dose limiting toxicities (DLTs) [28 days]
The Maximum Tolerated Dose (MTD) is defined as the dose at which 2 out of 3 to 6 patients experience a DLT.

Secondary Outcome Measures

Safety [whole study period]
Safety assessments include routine physical examinations and laboratory evaluations (blood cell counts, functional parameters and chemistry). Adverse events will be graded according to the NCI-CTCAE, Common Terminology Criteria for Adverse Events v.3.0.
Tumor response [every 2 months]
Tumor response in target and non-target lesions will be assessed according to the RECIST criteria.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically/ cytologically confirmed solid tumor that is metastatic or unresectable and for which standard curative or palliative chemotherapy measures do not exist or are no longer effective.
Histological/cytological diagnosis of solid tumors in which treatment with oral vinorelbine and oral platinum compounds(preferentially breast, NSCL, GU or GY tumors) is medically indicated
Progressive disease (also in terms of tumor markers only, like CA 125 for ovary and PSA for prostate). No measurable disease is necessary.
Age 18-75 years
Prior chemotherapy of ≤ 2 lines for advanced disease
ECOG Performance Status < 2
Life expectancy of at least 3 months
The patient or his/her legal representative must be able to read, understand and provide written evidence of informed consent
Female patients must not be pregnant or lactating and must be willing to practice contraception. The effects of satraplatin on the developing human fetus are unknown. For this reason, women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation.
Male patients that are not surgically sterile must be practicing a medically acceptable contraceptive regimen while on study treatment
Adequate organ function as defined by the following:

Serum creatinine < 1.5 mg/dl (< 132 umol/l)
ANC > 1500/microL
Hb > 10 g/dl
Platelet > 100,000/microL
Total bilirubin < ULN for the reference laboratory
AST and ALT and alkaline phosphatase (AP) must be within the designated range allowing for eligibility.

Exclusion Criteria:

Other chemotherapy treatment < 4 weeks prior to enrolment
Treatment with vinorelbine < 6 months from time of enrolment
Known resistance to platinum chemotherapy containing regimens (resistance is defined as PD while on treatment or a progression free interval < 6 months after completion of platinum therapy)
Known resistance to vinca alkaloids, treatment (including continuous infusion). Resistance is defined as PD while on treatment or a progression free interval < 6 months after completion of therapy
Hypersensitivity or allergic reactions to platinum compounds or vinorelbine
Radiotherapy involving > 30% of the active bone marrow
Radiotherapy < 4 weeks prior to enrolment
Pre-existing peripheral neuropathy > grade 1
Pre-existing CTCAE hearing loss or tinnitus ≥ grade 2
Metastatic brain or meningeal tumors unless the patient is > 6 months from definitive therapy, had a negative imaging study within 4 weeks of study entry, is clinically stable with respect to the tumor at the time of study entry, and is not receiving steroid therapy or taper
Patients who have not recovered (> grade 1) from the following toxicities of previous regimens before enrolment: fatigue, mucositis, nausea/vomiting, diarrhoea
Subject is currently enrolled in, or has not yet completed at least 30 days since ending other investigational device or drug trial(s) or is receiving other investigational agent(s)
Uncontrolled intercurrent illness including, but not limited to, ongoing active infection, uncontrolled congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness that would limit compliance with study requirements
Pre-existing malabsorption syndrome, irritable bowel syndrome or other clinical situation which could affect oral absorption
History of human immunodeficiency (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
Concurrent use of medications that inhibit cytochrome P450 3A4
History of bone marrow or major organ transplant
Prior high dose treatment with PBSC support