Cisplatin/Paclitaxel/Gemcitabine +/- Avastin in Patients With Unknown Primary Tumor

Randomized Fase II Trial: Comparing Cisplatin, Paclitaxel and Gemcitabine Versus Cisplatin, Paclitaxel, Gemcitabine and Avastin in Patients With Unknown Primary Tumors

The purpose of this study is to investigate the efficacy of Cisplatin, Paclitaxel, Gemcitabine +/- Avastin (Bevacizumab) in patients with unknown primary tumors.

Upon determination of eligibility, all patients will be randomly assigned to one of two treatment arms:

Arm A: Cisplatin, Paclitaxel and Gemcitabine

• Cisplatin 75 mg/m2 IV infusion, Day 1
• Paclitaxel 175 mg/m2 IV infusion, Day 1
• Gemcitabine 1000 mg/m2 IV infusion, Day 1 and 8

Arm B: Cisplatin, Paclitaxel, Gemcitabine and Avastin (Bevacizumab)

• Cisplatin 75 mg/m2 IV infusion, Day 1
• Paclitaxel 175 mg/m2 IV infusion, Day 1
• Gemcitabine 1000 mg/m2 IV infusion, Day 1 and 8
• Bevacizumab 7,5 mg/m2 IV infusion, Day 1

Patients will be stratified by number of metastatic sites (one versus two or more) and the level of Lactate Dehydrogenase (normal versus high).

The regimens will be repeated every 21 days.

Inclusion Criteria:

1. Unknown primary tumors
2. ECOG performance status 0-1
3. Adequate kidney, liver and bone marrow function
4. No prior chemotherapy
5. Life expectancy > 3 months

Exclusion Criteria:

1. The following specific syndromes:

   • Squamous carcinoma limited to cervical glands
   • Women with adenocarcinoma isolated to axillary nodes
   • Women with adenocarcinoma isolated to peritoneal involvements
   • Young men (<55 years) with growing mid-line tumors where a germ cell tumor could be expected
   • Neuroendocrine carcinomas

2. Tumor located close to major blood vessels and judged to possess a high risk of serious bleeding

3. Any significant cardiac disease

4. Clinically significant peripheral vascular disease

5. History of myocardial infarction or stroke within 6 months

6. Evidence of coagulopathy

7. Use of ASA, NSAIDs or clopidogrel

8. Pregnancy or breast feeding

9. Ongoing therapeutic anti-coagulation

10. Hypertension with blood pressure > 150/100 mmHg

11. Brain metastases