Sorafenib Monotherapy in Inoperable/Recurrent Germ Cell Carcinoma Refractory to Chemotherapy (GCT)

Sorafenib (NEXAVAR) Monotherapy in Patients With Inoperable/Recurrent Germ Cell Carcinoma Refractory to Chemotherapy

Germ cell tumors, a relatively rare disease, but most common malignancy in young males, occur most frequently in testis. The incidence is about 1%, but is increasing in the majority of developed countries. The testicular cancer is an extremely important oncological condition due to his high rate of 80-90% of curability, which can be achieved by combination of chemotherapy and surgery.

Some of 20-30% of patients will experience disease progression after first line cisplatin-based chemotherapy and salvage 2nd line conventional-dose cisplatin-based salvage chemotherapy will result in long term remissions in < 50% of patients (VeIP - vinblastine, ifosfamide, cisplatin, VIP/PEI - ifosfamide, etoposide, cisplatin, TIP - paclitaxel, ifosfamide, cisplatin). In multiple relapsed patients the 3rd line chemotherapy can induce remission in up to 40% (gemcitabine, oxaliplatin), 23% RR (TG - paclitaxel, gemcitabine), 20% CR (IPO - irinotecan, paclitaxel, oxaliplatin), but only small proportion of them can be cured, usually with subsequent consolidation surgery. At that stage the disease is usually chemorefractory and there are no other chemotherapy regimens of proven benefit (7).

The purpose of this study is to determine if multiple-relapsed chemorefractory pts may benefit from sorafenib monotherapy.

Study Overview

• Status: Unknown
• Conditions: Testicular Cancer
• Intervention / Treatment: Drug: sorafenib

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Iwona A Skoneczna, MD; Phone Number: +48225462098; Email: i.skoneczna@coi.waw.pl
• Study Contact Backup: Name: Agnieszka Chaladaj-Kujawska, MD; Phone Number: +48225462057

Study Locations

• Poland
  • Warsaw, Poland, 02781
    • Recruiting
    • Chemotherapy Unit, Dept of Urology, Instituite of Oncology
    • Principal Investigator: Iwona A Skoneczna, MD
    • Sub-Investigator: Agnieszka Chaladaj-Kujawska, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Male patients > 18 years of age
2. Patients with histologically proven germ cell neoplasm (gonadal or extragonadal primary)
3. Patients must have the disease not amendable to cure with either surgery or chemotherapy
4. Patients must have failed at least two cisplatin-based combination chemotherapy regimens.

5. Failure on prior regimens will be defined as either:

   • A ≥ 25% increase in sum of target lesions, new lesions, or
   • An increasing AFP or HCG above the nadir level.
6. Patients with at least one measurable lesion by CT scan or MRI according to RECIST criteria
7. Adequate bone marrow, liver and renal function, assessed no longer than 14 days before treatment start, defined by the following laboratory test limits: WBC > 2.0 x 109/l and platelets > 60 x 109/l, total bilirubin < 2 x upper limit, AST and ALT < 5 x upper limit normal, serum creatinine < 2 x UNL
8. WHO Performance Status 0, 1, 2
9. No concurrent chemotherapy or radiotherapy
10. Life expectancy of at least 12 weeks
11. Absence of any physiological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
12. A signed informed consent must be obtained prior to any study specific procedures
13. All patients must agree to use adequate contraception during the whole study period

Exclusion Criteria:

1. Patients not fulfilling of inclusion criteria
2. Primary radiotherapy in the field of target lesion
3. Major surgery (RPLND) within 4 weeks before the start of study drug or concurrent serious non-healing wounds, ulcers or bone fractures.
4. Known serious and active bacterial, viral or fungal infection (> grade II CTC-AE) including HBV, HCV and HIV carrier state.
5. Previous or concurrent malignancy except for basal cell carcinoma of the skin
6. Uncontrolled hypertension.
7. Thrombotic or embolic event in last 6 months prior to inclusion.
8. Impairment of gastrointestinal tract, or GI disease that may influence the bioavailability of oral sorafenib
9. Substance and alcohol abuse (nicotine use is allowed)
10. Known or suspected hypersensitivity to sorafenib.
11. Participants in any other clinical trial using investigational drug within 4 weeks prior to study entry
12. Prior use of investigational or licensed angiogenesis and RAF kinase or MEK inhibitors.
13. Patient unwilling or unable to give informed consent
14. Any condition that may in the investigator's opinion jeopardize the safety of the patient or his compliance in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: sorafenib; drug	Drug: sorafenib; tablets 200mg, 400mg bid continuously in 4-week cycles; Other Names: Nexavar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression free survival	one year

Secondary Outcome Measures

Outcome Measure	Time Frame
ORR Evaluation of the usefulness the CT with vasculature visualisation option in the measurement of the objective response Evaluation of quality of life	one year

Collaborators and Investigators

• Sponsor: Fondation Wygrajmy Zdrowie

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Anticipated): December 1, 2011
• Study Completion (Anticipated): December 1, 2011

Study Registration Dates

• First Submitted: October 14, 2008
• First Submitted That Met QC Criteria: October 14, 2008
• First Posted (Estimate): October 15, 2008

Study Record Updates

• Last Update Posted (Estimate): October 24, 2008
• Last Update Submitted That Met QC Criteria: October 23, 2008
• Last Verified: October 1, 2008

More Information

Terms related to this study

• Keywords: sorafenib; germ cell cancer; testicular cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Endocrine System Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Genital Neoplasms, Male; Testicular Diseases; Testicular Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: 12602; PL/ 183/UR/CEBK/04/08; EudraCT 2007-007599-40