Pemetrexed and Oxaliplatin in Treating Patients With Locally Advanced Head and Neck Cancer

Head and Neck Cancer Clinical Trial

Official title:

Phase II Trial: Efficacy and Toxicity of Induction Pemetrexed (ALIMTA) and Oxaliplatin (ELOXATIN) in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00503997
• Other study ID #: VICC HN 0582
• Secondary ID: VU-VICC-HN-0582V
• Status: Completed
• Phase: Phase 2
• First received: July 17, 2007
• Last updated: May 7, 2012
• Start date: December 2006
• Est. completion date: June 2010

Study information

• Verified date: May 2012
• Source: Vanderbilt-Ingram Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving pemetrexed together with oxaliplatin may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving pemetrexed together with oxaliplatin works in treating patients with locally advanced head and neck cancer.

Description:

OBJECTIVES:

Primary

• To evaluate the clinical response rate in patients with locally advanced squamous cell carcinoma of the head and neck treated with neoadjuvant pemetrexed disodium and oxaliplatin.

Secondary

• To evaluate the pathological complete response in patients who undergo surgical resection or post-induction biopsy.

• To assess toxicity of therapy, including the assessment of quality of life, fatigue, and head and neck cancer-related symptoms.

• To predict response and toxicities based on pharmacogenomics, genomics, and proteomics.

OUTLINE: This is a nonrandomized, open-label study. Patients are assigned to 1 of 2 groups based on resectability of disease (resectable vs nonresectable).

• Group I (resectable disease): Patients receive pemetrexed disodium IV and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 14 days for up to 4 courses. If patient progresses before receiving 4 courses of treatment, treatment will be discontinued and patient will proceed to surgery.

After completion of pemetrexed disodium and oxaliplatin, patients undergo surgical resection of disease.

• Group II (nonresectable disease): Patients receive treatment as in group I. If patient progresses before receiving 4 courses of treatment, treatment will be discontinued and patient will proceed to concurrent chemoradiotherapy.

After completion of pemetrexed disodium and oxaliplatin, patients undergo concurrent chemoradiotherapy.

Blood samples are collected at baseline and periodically during study for biomarker and pharmacokinetic studies.

Quality of life is assessed prior to each course of therapy and at 4-6 weeks after the last course.

After completion of study treatment, patients are followed periodically for up to 3 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: June 2010
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

Inclusion criteria:

Patients must meet all of the following criteria in order to be eligible for entry into the trial:

• Histologically or cytologically confirmed stage III - IVB HNSCC (includes unknown primary and ParaNasal Sinus cancers)but excludes nasopharyngeal, salivary gland or skin primaries (No TNM staging required)

• Patients must have a measurable disease defined by RECIST criteria

• Age > 18 years

• ECOG Performance Score of 0, 1 or 2

• Adequate bone marrow as evidenced by:

• Absolute neutrophil count > 1,500/µL

• Platelet count > 100,000/µL

• Adequate renal function as evidenced by serum creatinine < 1.5 mg/dL and CrCl > 45 mL/min as determined by calculated creatinine clearance using the Cockroft-Gault formula:

• CrCl = (140-age) x (weight in kg)/72 x serum creatinine

• Multiply by 0.85 (85%) for females

• Adequate hepatic function as evidenced by:

• Serum total bilirubin < 1.5 mg/dL

• Alkaline phosphatase < 3X the ULN for the reference lab

• SGOT/SGPT < 3X the ULN for the reference lab

• Patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial.

• Patients of childbearing potential and their partners must agree to use an effective form of contraception during the study and for 90 days following the last dose of study medication (an effective form of contraception is an oral contraceptive, double barrier method or surgical intervention resulting in sterility).

• Patients must be able to interupt NSAIDs at 2 days before (5 days for long-acting NSAIDs),the day of, and 2 days following administration of Pemetrexed.

• Patients must be willing and able to take Folic Acid (350-1000 µg) daily beginning 1 week (7 days) prior to the first dose of Pemetrexed and continued daily until 3 weeks after the last dose of study therapy. In addition, patients must be willing to maintain a Pill Diary as part of study compliance.

• Patients must be willing and able to take Vitamin B12 (1000 µg) administered intramuscularly beginning 1 week (7 days) prior to the first dose of Pemetrexed and repeated at the planned End of Treatment visit (no later than 9 weeks from the first injection).

• Patients must be willing and able to take Dexamethasone (4 mg of oral or equivalent) that should be given twice daily on the day before, the day of, and the day after each dose of Pemetrexed for rash prophylaxis unless medically contraindicated.

Exclusion Criteria:

A patient may not be enrolled in the trial if any of the following criteria are met:

• Patients with an active infection or with a fever > 101.30 F within 3 days of the first scheduled day of protocol treatment

• History of prior malignancy within the past 3 years except for curatively treated basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or localized prostate cancer with a current PSA of < 1.0 mg/dL on 2 successive evaluations, at least 3 months apart, with the most recent evaluation no more than 4 weeks prior to entry

• Patients with known hypersensitivity to any of the components of Oxaliplatin and Pemetrexed

• Patients who received any chemotherapy, radiation therapy or surgical resection other than diagnostic biopsies for HNSCC prior to the first scheduled day of protocol treatment

• Patients who are receiving concurrent investigational therapy or who have received investigational therapy within 30 days of the first scheduled day of protocol treatment(investigational therapy is defined as treatment for which there is currently no regulatory authority approved indication)

• Peripheral neuropathy = Grade 2

• Patients who are pregnant or lactating

• Any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent,cooperate and participate in the study, or interferes with the interpretation of the results.

• History of allogeneic transplant

• Known HIV (active, previously treated or both)

• Presence of clinically detectable (by physical exam) third-space fluid collections, for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study entry.

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Drug:
• oxaliplatin
Group I: Patients receive pemetrexed disodium IV and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 14 days for up to 4 courses. If patient progresses before receiving 4 courses of treatment, treatment will be discontinued and patient will proceed to surgery. Group II: Patients receive treatment as in group I. If patient progresses before receiving 4 courses of treatment, treatment will be discontinued and patient will proceed to concurrent chemoradiotherapy.
• pemetrexed disodium
Group I: Patients receive pemetrexed disodium IV and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 14 days for up to 4 courses. If patient progresses before receiving 4 courses of treatment, treatment will be discontinued and patient will proceed to surgery. Group II: Patients receive treatment as in group I. If patient progresses before receiving 4 courses of treatment, treatment will be discontinued and patient will proceed to concurrent chemoradiotherapy.

Locations

Country	Name	City	State
United States	West Tennessee Cancer Center at Jackson-Madison County General Hospital	Jackson	Tennessee
United States	MBCCOP - Meharry Medical College - Nashville	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center - Cool Springs	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center at Franklin	Nashville	Tennessee
United States	Mitchell Memorial Cancer Center at Owensboro Medical Health System	Owensboro	Kentucky
United States	Purchase Cancer Group - Paducah	Paducah	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt-Ingram Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patient Response to Treatment Measured by RECIST Criteria	RECIST response categories: Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.	at 8 weeks	No