Nelfinavir in Recurrent Adenoid Cystic Cancer of the Head and Neck

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.

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.