Nelfinavir in Recurrent Adenoid Cystic Cancer of the Head and Neck

• Sponsor: University of Iowa (Other)
• Overall Status: Completed
• CT.gov ID: NCT01065844
• Collaborator: Holden Comprehensive Cancer Center (Other)
• Enrollment: 15
• Location: 1
• Arm: 1
• Actual Duration (Months): 97
• Patients Per Site Per Month: 0.2

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Adenoid Cystic; Head and Neck Neoplasms	Drug: Nelfinavir	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Actual Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: Nov 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nelfinavir 1250 mg Nelfinavir twice daily Monday-Sunday	Drug: Nelfinavir; 1250 mg Nelfinavir twice daily Monday - Sunday

Outcome Measures

Primary Outcome Measures

1. Tumor Progression [Every 1 to 3 months]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	The Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242

Sponsors and Collaborators

• University of Iowa
• Holden Comprehensive Cancer Center

Investigators

• Principal Investigator: John M. Buatti, M.D., University of Iowa

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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. Epub 2009 Oct 22.

• Responsible Party: John M. Buatti, Professor & Chair of Radiation Oncology, University of Iowa
• ClinicalTrials.gov Identifier: NCT01065844
• Other Study ID Numbers: 200905704
• First Posted: Feb 9, 2010
• Last Update Posted: Oct 9, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by John M. Buatti, Professor & Chair of Radiation Oncology, University of Iowa: Nelfinavir
• Additional relevant MeSH terms: Head and Neck Neoplasms; Carcinoma, Adenoid Cystic; Nelfinavir

Study Results

Participant Flow

Arm/Group Title	Nelfinavir
Arm/Group Description	1250 mg Nelfinavir twice daily Monday-Sunday Nelfinavir: 1250 mg Nelfinavir twice daily Monday - Sunday
Period Title: Overall Study
STARTED	15
COMPLETED	10
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Nelfinavir
Arm/Group Description	1250 mg Nelfinavir twice daily Monday-Sunday Nelfinavir: 1250 mg Nelfinavir twice daily Monday - Sunday
Overall Participants	15
Age, Customized (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	12 80%
>=65 years	3 20%
Sex/Gender, Customized (Count of Participants)
Female	9 60%
Male	6 40%
Region of Enrollment (participants) [Number]
United States	15 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Those with adverse events necessitating interruption of intervention and removal from study were not assessed for outcome measures

Arm/Group Title	Nelfinavir
Arm/Group Description	1250 mg Nelfinavir twice daily Monday-Sunday Nelfinavir: 1250 mg Nelfinavir twice daily Monday - Sunday
Measure Participants	11
Complete reponse (CR)	0 0%
Partial response (PR)	0 0%
Stable disease (SD)	7 46.7%
Progressive disease (PD)	4 26.7%

Adverse Events

Time Frame	Adverse event data collected from day 1 of nelfinavir therapy through 30 days after final nelfinavir dose.
Arm/Group Title	Nelfinavir
Arm/Group Description	1250 mg Nelfinavir twice daily Monday-Sunday Nelfinavir: 1250 mg Nelfinavir twice daily Monday - Sunday
All Cause Mortality
	Nelfinavir
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Nelfinavir
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Other (Not Including Serious) Adverse Events
	Nelfinavir
	Affected / at Risk (%)	# Events
Total	5/15 (33.3%)
Blood and lymphatic system disorders
platelet count decreased	1/15 (6.7%)	1
Investigations
Investigations - Other, liver enzymes increased, grade 3	2/15 (13.3%)	2
Metabolism and nutrition disorders
hyponatremia, grade 4	1/15 (6.7%)	1
Nervous system disorders
dizziness, grade 3	1/15 (6.7%)	1

Limitations/Caveats

Favorable selection criteria were used in study design. RECIST assessed at a median interval of 12 weeks - this difference in methods may have artificially prolonged the progression free survival observed in this study.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.