Nelfinavir in Recurrent Adenoid Cystic Cancer of the Head and Neck

Nelfinavir in Recurrent Adenoid Cystic Cancer of the Head and Neck
This study is currently recruiting participants.
Verified March 2012 by University of Iowa

First Received on February 8, 2010.  
Last Updated on March 29, 2012  
History of Changes
Sponsor: University of Iowa
Collaborator: Holden Comprehensive Cancer Center
Information provided by (Responsible Party): John M. Buatti, University of Iowa
ClinicalTrials.gov Identifier: NCT01065844
  Purpose

The purpose of this study is to evaluate the FDA-approved drug nelfinavir (NFV) as an oncologic agent for adenoid cystic cancers of the head and neck.

Specifically, subjects will be asked to take 1250 mg twice daily and follow-up with their medical oncologist as clinically indicated while taking this medication.

Subjects would be evaluated for quality of life issues utilizing the EORTC QLQ-C30 2-page questionnaire.

Subjects would also be evaluated clinically by the oncologist to determine if the NFV was having an anti-neoplastic effect.

The study remains unfunded. Therefore, potential subjects must be willing to provide self-travel to study site. This study requires a screening visit, initial study visit, and monthly follow-up. Subjects are not reimbursed for time, travel, or physician costs.

Condition Intervention Phase
Carcinoma, Adenoid Cystic
Head and Neck Neoplasms
Drug: Nelfinavir Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of the HIV Protease Inhibitor Nelfinavir in Patients With Recurrent Symptomatic Adenoid Cystic Cancers of the Head and Neck

Resource links provided by NLM:

Further study details as provided by University of Iowa:

Primary Outcome Measures:

  • Tumor progression [ Time Frame: Every 1 to 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

  • Quality of Life [ Time Frame: every 1 to 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 35
Study Start Date: October 2009
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

Arms

Assigned Interventions
Experimental: Nelfinavir

1250 mg Nelfinavir twice daily Monday-Sunday
Drug: Nelfinavir

1250 mg Nelfinavir twice daily Monday – Sunday

Detailed Description:

The hypothesis of this study is that nelfinavir, by inhibiting the Akt and MAPK pathways, can inhibit adenoid cystic carcinoid growth. These cancers are heavily dependent on these signalling pathways.

Adenoid cystic carcinomas (ACC) are rare and account for about 1% of all head and neck cancers. They stem from salivary glands and are known for their tendency to spread along nerve sheaths (perineural spread). ACC is known for its prolonged clinical course, multiple recurrence and the delayed onset of distant metastases. The median/mean age at presentation is 47-56. Although 5 year disease free survivals (DFS) are 65-70%, the 15 year DFS drops to 30-40%. If followed long enough, 35% of patients will eventually develop metastatic disease.

The most common treatment of ACC is surgery followed by post-operative radiotherapy. When ACC recurs, management options are often limited both by the morbidity and low efficacy of re-irradiation and repeated surgical resection. Reported response rates to chemotherapy are low and when it occurs, the duration of the response is short lived.

In an effort to explore possible targeted therapies for patients with recurrent ACC, Dr. Gupta’s lab examined the activation of 3 signaling proteins (EGFR, Akt, and MAPK) in 9 different paraffinized tissue blocks. Initial indications from in vitro studies demonstrates NFV is tumoricidal at clinically achievable concentrations. To explore the clinical benefit of this FDA-approved medication, we seek to implement its off label use in patients who have failed all other therapies and have no other therapeutic options left.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histological diagnosis of adenoid cystic carcinoma.
  • Cancer should be staged recurrent or end-stage with/without metastases who have failed all other therapy.
  • Age ≥ 18 years
  • ECOG performance status 0-2 (Karnofsky ≥ 50%, see Appendix A).
  • Patients must have normal organ and marrow function as defined below:

    • leukocytes ≥ 3,000/mm3
    • absolute neutrophil count ≥ 1,500/mm3
    • platelets ≥ 100,000/mm3
    • total bilirubin < 1.5 mg/dl OR a stable or a decreasing bilirubin in patients who have undergone placement of an intrabiliary stent
    • AST(SGOT) ≤ 2.5 X institutional upper limit of normal
    • ALT(SGPT) ≤ 2.5 X institutional upper limit of normal
    • creatinine < 1.5 X institutional upper limit of normal OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
  • No known HIV infection. Since NFV is used in HIV patients, we do not want to interfere with the therapy the patient may already be on.
  • Not pregnant. The effects of NFV on the developing human fetus have been studied in HIV positive women (21). We do not, however, know the risks along with radiation. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to NFV.
  • Uncontrolled diabetes.
  • Hemophilia A & B as increased bleeding during protease inhibitor therapy has been reported (22).
  • Patients may not be receiving any other investigational agents. concomitant medications counterindicated for use with nelfinavir
  • Pregnant or lactating women: The effects of NFV on the developing human fetus have been studied in HIV positive women (21). In addition, the chemotherapy will be deleterious to the fetus.
  • HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with NFV.
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01065844

Contacts
Contact: Jane M. Hershberger, RN, BSN (319) 384-7912 jane-hershberger@uiowa.edu
Contact: Sandy Vollstedt, RN, BSN 319 353 7143 sandy-vollstedt@uiowa.edu

Locations
United States, Iowa
The Holden Comprehensive Cancer Center Recruiting
Iowa City, Iowa, United States, 52242
Contact: Jane M. Hershberger, RN, BSN     319-384-7912     jane-hershberger@uiowa.edu    
Contact: Sandy Vollstedt, RN, BSN     319 353 7143     sandy-vollstedt@uiowa.edu    
Principal Investigator: John M. Buatti, M.D.            
Sub-Investigator: Mohammed M Milhem, M.D.            
Sponsors and Collaborators
University of Iowa
Holden Comprehensive Cancer Center
Investigators
Principal Investigator: John M. Buatti, M.D. The University of Iowa
  More Information

Publications:

Responsible Party: John M. Buatti, Professor & Chair of Radiation Oncology, University of Iowa
ClinicalTrials.gov Identifier: NCT01065844    
History of Changes
Other Study ID Numbers: 200905704
Study First Received: February 8, 2010
Last Updated: March 29, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of Iowa:

Nelfinavir

Additional relevant MeSH terms:

Neoplasms
Carcinoma
Carcinoma, Adenoid Cystic
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Neoplasms by Site
Protease Inhibitors
Nelfinavir
HIV Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 21, 2012

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