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Nelfinavir in Recurrent Adenoid Cystic Cancer of the Head and Neck

Primary Purpose

Carcinoma, Adenoid Cystic, Head and Neck Neoplasms

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Nelfinavir
Sponsored by
University of Iowa
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Adenoid Cystic focused on measuring Nelfinavir

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The Holden Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Nelfinavir

Arm Description

1250 mg Nelfinavir twice daily Monday-Sunday

Outcomes

Primary Outcome Measures

Tumor Progression
Tumor progression as defined by RECIST version v1.1 criteria with ordinal measurements of complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD).

Secondary Outcome Measures

Full Information

First Posted
February 8, 2010
Last Updated
September 24, 2019
Sponsor
University of Iowa
Collaborators
Holden Comprehensive Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT01065844
Brief Title
Nelfinavir in Recurrent Adenoid Cystic Cancer of the Head and Neck
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
October 2009 (Actual)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
November 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Iowa
Collaborators
Holden Comprehensive Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Adenoid Cystic, Head and Neck Neoplasms
Keywords
Nelfinavir

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Nelfinavir
Arm Type
Experimental
Arm Description
1250 mg Nelfinavir twice daily Monday-Sunday
Intervention Type
Drug
Intervention Name(s)
Nelfinavir
Intervention Description
1250 mg Nelfinavir twice daily Monday - Sunday
Primary Outcome Measure Information:
Title
Tumor Progression
Description
Tumor progression as defined by RECIST version v1.1 criteria with ordinal measurements of complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD).
Time Frame
Every 1 to 3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John M. Buatti, M.D.
Organizational Affiliation
University of Iowa
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Holden Comprehensive Cancer Center
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
19729990
Citation
Gupta AK, Wilke WW, Taylor EN, Bodeker KL, Hoffman HT, Milhem MM, Buatti JM, Robinson RA. Signaling pathways in adenoid cystic cancers: implications for treatment. Cancer Biol Ther. 2009 Oct;8(20):1947-51. doi: 10.4161/cbt.8.20.9596. Epub 2009 Oct 22.
Results Reference
background
PubMed Identifier
24596143
Citation
Hoover AC, Milhem MM, Anderson CM, Sun W, Smith BJ, Hoffman HT, Buatti JM. Efficacy of nelfinavir as monotherapy in refractory adenoid cystic carcinoma: Results of a phase II clinical trial. Head Neck. 2015 May;37(5):722-6. doi: 10.1002/hed.23664. Epub 2014 Jun 18.
Results Reference
result

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Nelfinavir in Recurrent Adenoid Cystic Cancer of the Head and Neck

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