Clinical trial NCT00736944
Conditions: Squamous Cell Carcinoma of the Head and Neck
Sponsor: Washington University School of Medicine
Start date: 2008-12-19; Completion date: 2020-07-06
Enrollment: 30 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
This phase two trial will determine the tumor response rate at the primary site and at involved regional nodes to two cycles of an IC regimen of weekly Abraxane and cetuximab given in combination with cisplatin and 5-FU in patients with local regionally advanced HNSCC.

Detailed description:
Primary objective:

To determine the clinical CR rate (CR-p) at the primary tumor site to an IC regimen of weekly Abraxane and cetuximab with CF (ACCF) given for two cycles (over 6 weeks) in patients with locally advanced non-metastatic HNSCC. The assessment of primary tumor site response will be performed by the treating physician by careful clinical examination using WHO criteria. Radiographic studies will also be performed to assess primary tumor site response but will be used primarily to confirm lack of disease progression that may not be detected based on clinical examination alone.

The secondary objectives include:

* Document the clinical PR rate (PR-p) at the primary tumor site with this IC regimen
* Document the clinical CR and PR rates at the involved regional nodes (CR-n and PR-n) with this IC regimen
* Document the clinical overall CR rate (CR-o) (defined as achievement of a CR at the primary tumor site and at the involved regional nodes) and the clinical overall PR rate (PR-o) with this IC regimen
* Document the CR (CR-p, CR-n, and CR-o) and PR (PR-p, PR-n, and PR-o) rates by FDG uptake on PET scan after this IC regimen
* Document radiographic CR (CR-p, CR-n, and CR-o) and PR (PR-p, PR-n, and PR-o) rates as assessed by conventional CT scan using RECIST criteria after this IC regimen.
* Correlate primary tumor site, nodal and overall tumor response rates based on WHO criteria of assessment with that based on CT scan and FDG-PET/CT.
* Document and quantify SPARC expression by IHC in primary tumor tissue obtained at baseline in each patient and attempt to correlate these results with primary tumor site response to ACCF.
* Document and grade AE's with this IC regimen with a pre-planned safety analysis after the first ten patients have completed the IC regimen.
* Determine the overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) of this patient population.

Arms: arm 1: Induction chemotherapy followed by Radiation therapy plus Cisplatin

Induction chemotherapy:

Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3.

Post-Induction:

Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42. arm 2: Induction chemotherapy followed by Radiation therapy plus Cetuximab

Induction chemotherapy:

Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3.

Post-Induction:

Radiation - Monday-Friday weeks 1-7 with concurrent Cetuximab (for patients who cannot receive cisplatin) will begin (+/- 3 days) before starting radiation therapy at 400 mg/m2 IVPB. Subsequent doses of cetuximab will be given weekly at 250 mg/m2 IVPB
Interventions: intervention 1: Abraxane intervention 2: Cetuximab intervention 3: Cetuximab intervention 4: Cisplatin intervention 5: 5-FU intervention 6: Radiation (Post induction) intervention 7: Cisplatin intervention 8: Cetuximab
Intervention descriptions: intervention 1: 100 mg/m2 IVPB, Day 1, 8 and 15 of cycles 1, 2, and 3 intervention 2: 400 mg/m2 IVPB, Day 1, cycle 1 intervention 3: 250 mg IVPB, Day 8 and 15 cycle 1, Day 1, 8 and 15 of cycles 2 and 3 intervention 4: 75 mg/m2 IVPB Day 1, cycles 1, 2 and 3 intervention 5: 750 mg/m2 CIVI Day 1, 2 and 3, cycles 1, 2 and 3 intervention 6: Monday-Friday, weeks 1-7 intervention 7: (Post induction) Cisplatin 100 mg/m2 IVPB on radiation day 1, 22 and 42 intervention 8: (Post-induction) Cetuximab (for patients who cannot receive cisplatin) will begin (+/- 3 days) before starting radiation therapy at 400 mg/m2 IVPB. Subsequent doses of cetuximab will be given weekly at 250 mg/m2 IVPB

Protocol documents: