Study of Pemetrexed and Bevacizumab in Patients With Head and Neck Cancer

Phase II Trial of Pemetrexed and Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer

The purpose of this study is to determine if the combination of two new drugs pemetrexed (Alimta) and bevacizumab (Avastin) can increase the effectiveness of treatment for head and neck cancer. Currently pemetrexed is approved by the Food and Drug Administration (FDA) for another type of cancer, mesothelioma, but it is not approved for head and neck cancer.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: Pemetrexed; Drug: Bevacizumab

Detailed Description

Main objectives of this study are to 1) evaluate the time to progression (primary endpoint) with the combination of pemetrexed and bevacizumab in recurrent or metastatic head and neck cancer; 2) evaluate the objective response rate, duration of response, overall survival, and toxicities associated with the above therapy and 3) collect tumor tissue from previous diagnostic procedures and blood specimens prospectively, before and after therapy, for future correlative studies.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15216
      • Hillman Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Metastatic or locally recurrent squamous cell carcinoma of the head and neck. Patients with local recurrence will be considered incurable by means of locoregional therapy, as judged by the investigator.
2. Cytologically or histologically confirmed squamous cell carcinoma. Nasopharyngeal carcinoma of histologic subtype WHO II and III will be excluded.
3. Unidimensional measurable disease (RECIST criteria). If the only site of measurable disease is in a previously irradiated area, the patient must have documented progression of disease in this area.
4. ECOG performance status 0-1.
5. Full recovered from the effects of any prior surgery, or radiation therapy. A minimum time period of 3 weeks will elapse between the completion of extensive radiation therapy for recurrent/metastatic disease and enrollment in the study

6. Laboratory values:

   ANC ³ 1500/mm³. Platelets ³ 100,000/mm³. Total Bilirubin within normal institutional limits.

7. Transaminases (AST and ALT) < 3 x ULN. Creatinine clearance 45 ml/min or higher calculated using the Cockcroft-Gault formula.
8. Urine protein to creatinine (UPC) ratio of ≤ 1.0 on spot urine urinalysis.
9. Age > 18 years and capacity to give informed consent.

Exclusion Criteria:

1. Prior chemotherapy or biologic therapy for recurrent/metastatic head and neck cancer.
2. Prior pemetrexed, bevacizumab, or other antiangiogenesis agents at any time.
3. Presence of tumors that invaded major vessels.
4. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment, or anticipation of need for major surgical procedure during the course of the study
5. Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to study enrollment.
6. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to registration. Serious non-healing wound, ulcer, or bone fracture.
7. History of brain metastasis or seizures.
8. Prior malignancy, with the exception of curatively treated squamous cell or basal carcinoma of the skin or in situ cervical cancer, unless there is a 5-year disease-free interval.
9. Pre-existing peripheral neuropathy > grade 2.
10. Myocardial infarction or stroke in the last 6 months. Unstable angina; Heart Association (NYHA) Grade II or greater congestive heart failure; Clinically significant peripheral vascular disease; CNS cerebrovascular ischemia within the last 6 months; active serious infection; other coexisting medical condition that would preclude full compliance with the study
11. Bleeding diathesis or coagulopathy.
12. Therapeutic anticoagulation (prophylactic use of warfarin 1 mg per day is allowed) or INR greater than 1.5 at registration
13. History of gross hemoptysis (defined as bright red blood of a ½ teaspoon or more).
14. Uncontrolled hypertension (>150/100)
15. Pregnant or lactating.
16. Use of NSAIDs within 5 days of protocol therapy.

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: Pemetrexed & Bevacizumab	Drug: Pemetrexed; 500 mg/m2 day 1 q 21 days; Other Names: (N-[4-[2-(2-amino-3,4-dihydron-4-oxo-7H-pyrolo[2,3-d]pyrinidin-5-yl)ethyl]benzoyl]-L-glutamic acid), Alimta, pemetrexed disodium, LY231514, MTA; Drug: Bevacizumab; 15 mg/kg IV q 21 days following pemetrexed; Other Names: NSC 704865, RhuMAb VEGF, Bevacizumab, Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-to-progression (TTP)	TTP was calculated from treatment initiation to disease progression or last follow-up.	Up to 36 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival (OS)	Up to 36 months
Objective Response Rate (ORR)	Up to 36 months
Disease Control Rate (DCR)	Up to 36 months

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: Eli Lilly and Company; Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: September 16, 2005
• First Submitted That Met QC Criteria: September 16, 2005
• First Posted (Estimate): September 22, 2005

Study Record Updates

• Last Update Posted (Estimate): February 15, 2016
• Last Update Submitted That Met QC Criteria: January 15, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: head; neck
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Folic Acid Antagonists; Bevacizumab; Pemetrexed
• Other Study ID Numbers: 05-002; 12,158