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CompletedNCT00589056Updated Apr 24, 2020Results posted

Nelfinavir, Radiation Therapy, Cisplatin, and Etoposide in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

A Phase 1/2 interventional study of cisplatin and etoposide in Lung Cancer, sponsored by Abramson Cancer Center at Penn Medicine. Completed at 1 site in United States. Open to participants aged 18 Years to 120 Years. Per ClinicalTrials.gov, last updated 2020-04-24.

Sponsored by Abramson Cancer Center at Penn Medicine · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
55
Allocation
Not applicable
Ages
18 Years to 120 Years
Sex
All
01

Study summary

RATIONALE: Nelfinavir may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells. Nelfinavir may make tumor cells more sensitive to radiation therapy. Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving nelfinavir together with radiation therapy, cisplatin, and etoposide may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of nelfinavir when given together with radiation therapy, cisplatin, and etoposide and to see how well they work in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery.

Read the detailed description

OBJECTIVES:

Primary

  • To determine the dose-limiting toxicities, maximum tolerated dose, and recommended phase II dose of nelfinavir mesylate when administered in combination with concurrent thoracic radiotherapy, cisplatin, and etoposide in patients with unresectable locally advanced non-small cell lung cancer.

Secondary

  • To determine the tumor response at 3 months after completion of treatment as measured by RECIST criteria.
  • To assess the inhibition of p-Akt in primary tumor or pathologic lymph nodes and in peripheral blood lymphocytes after 5-10 days of treatment with nelfinavir mesylate.
  • To determine the median overall survival (OS) of patients treated with this regimen.
  • To compare the observed median OS of these patients with the historical median OS of 17 months.

OUTLINE: This is a phase I, dose-escalation study of nelfinavir mesylate followed by a phase II study.

  • Phase I: Patients receive oral nelfinavir mesylate twice daily beginning 1-2 weeks before the initiation of chemoradiotherapy and continuing until the completion of radiotherapy. Patients undergo thoracic radiotherapy once daily 5 days a week for 7-8 weeks. Patients also receive cisplatin IV on days 1, 8, 29, and 36 and etoposide IV on days 1-5 and 29-33. After completion of chemoradiotherapy, patients receive two additional courses of cisplatin and etoposide.
  • Phase II: Patients receive nelfinavir mesylate at the maximum tolerated dose determined in phase I and concurrent chemoradiotherapy as in phase I.

Patients undergo blood sample collection periodically for correlative laboratory studies. Patients treated in the phase II portion of the study and those with primary tumors or pathologic lymph nodes easily accessible by core biopsy or mediastinoscopy also undergo tumor tissue biopsies. Blood and tumor tissue samples are analyzed for expression of molecular markers (total Akt and p-Akt ) by immunohistochemistry. The molecular markers are correlated with treatment response.

After completion of study treatment, patients are followed at 3, 6, and 12 months.

02

Conditions studied

  • Lung Cancer

Keywords

  • stage IIIA non-small cell lung cancer
  • stage IIIB non-small cell lung cancer
  • recurrent non-small cell lung cancer
03

In context

Lung Neoplasms

7,243 studies on the registry are indexed under Lung Neoplasms; 1,557 are open to participants now.

This study's enrollment of 55 is close to the median of 60 across 5,295 interventional studies indexed under Lung Neoplasms.

Browse Lung Neoplasms studies →

Lead sponsor

Abramson Cancer Center at Penn Medicine is the lead sponsor of 446 studies on the registry; 86 are open to participants now.

Of its 32 completed or terminated interventional studies of FDA-regulated products, 14 (44%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 120 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed non-small cell lung cancer

    • Locally advanced (stage III) disease
    • Unresectable disease
  • Candidate for concurrent definitive chemotherapy and thoracic radiotherapy, as determined by the treating physician
  • No malignant pleural effusion

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Absolute neutrophil count > 1,500/mm³
  • Platelet count > 100,000/mm³
  • Bilirubin ≤ 1.5 mg/dL
  • AST or ALT ≤ 2 times upper limit of normal (ULN)
  • Creatinine ≤ 1.5 times ULN
  • FEV_1 > 600 cc
  • Not pregnant or nursing
  • Negative pregnancy test
  • No weight loss > 10% within the past 6 months
  • No known HIV disease

PRIOR CONCURRENT THERAPY:

  • No prior thoracic radiotherapy
  • No prior HIV protease inhibitors
  • More than 5 years since prior chemotherapy
  • At least 3 weeks since prior exploratory thoracotomy

  • No concurrent medications that would preclude nelfinavir administration, including any of the following:

    • Amiodarone
    • Quinidine
    • Rifampin
    • Dihydroergotamine
    • Ergonovine
    • Ergotamine
    • Methylergonovine
    • Hypericum perforatum (St. John's wort)
    • Lovastatin
    • Simvastatin
    • Pimozide
    • Midazolam
    • Triazolam
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
55 participants (actual)

Study arms

  • Experimental
    Single arm

    Nelfinavir

    Drug: cisplatin · Drug: etoposide · Drug: nelfinavir mesylate · Genetic: protein expression analysis · Other: immunohistochemistry staining method · Other: laboratory biomarker analysis · Procedure: biopsy · Radiation: radiation therapy

Interventions

  • Drugcisplatin
  • Drugetoposide
  • Drugnelfinavir mesylate
  • Geneticprotein expression analysis
  • Otherimmunohistochemistry staining method
  • Otherlaboratory biomarker analysis
  • Procedurebiopsy
  • Radiationradiation therapy
06

What researchers measure

Primary outcomes

  1. Dose-limiting Toxicity

    Any grade III or higher toxicity during chemoradiation, per CTCAE

    Time frame: 90 days

  2. Maximum Tolerated Dose of Nelfinavir

    As determined by dose escalation rules

    Time frame: 90 days

Secondary outcomes

  1. Clinical Response of Tumor

    Tumor size as determined by imaging

    Time frame: 90 days

07

Results

Posted Apr 24, 2020

Participant flow

Participant flow — Overall Study
MilestoneSingle Arm
Started55
Completed52
Not completed3

Outcome measures

PrimaryDose-limiting Toxicity

Any grade III or higher toxicity during chemoradiation, per CTCAE

Time frame:
90 days
Reported as:
Number · Dose-limiting toxicities
Dose-limiting Toxicity
Dose-limiting toxicitiesSingle Arm
Dose-limiting Toxicity0
PrimaryMaximum Tolerated Dose of Nelfinavir

As determined by dose escalation rules

Time frame:
90 days
Reported as:
Number · mg PO twice daily
Maximum Tolerated Dose of Nelfinavir
mg PO twice dailySingle Arm
Maximum Tolerated Dose of Nelfinavir1250
SecondaryClinical Response of Tumor

Tumor size as determined by imaging

Time frame:
90 days
Reported as:
Number · percentage of participants
Clinical Response of Tumor
percentage of participantsSingle Arm
Clinical Response of Tumor94 (86 to 100)

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Single Arm3/55 (5.5%)21/55 (38.2%)40/55 (72.7%)
Most frequent serious events
Showing 10 of 30
Most frequent serious events
EventSingle Arm
LeukocytesBlood and lymphatic system disorders9/55
ANCBlood and lymphatic system disorders3/55
Chest PainMusculoskeletal and connective tissue disorders3/55
DehydrationGastrointestinal disorders3/55
Febrile neutropeniaInfections and infestations3/55
PneumoniaRespiratory, thoracic and mediastinal disorders3/55
Decreased ANCBlood and lymphatic system disorders2/55
EsophagitisGastrointestinal disorders2/55
FatigueGeneral disorders2/55
Infection, Lung (pneumonia)Infections and infestations2/55
Most frequent other events
Showing 10 of 190
Most frequent other events
EventSingle Arm
EsophagitisGastrointestinal disorders34/55
FatigueGeneral disorders33/55
HyponatremiaBlood and lymphatic system disorders31/55
NauseaGastrointestinal disorders30/55
ConstipationGastrointestinal disorders26/55
HyperglycemiaMetabolism and nutrition disorders26/55
HypoalbuminemiaMetabolism and nutrition disorders26/55
HypocalcemiaMetabolism and nutrition disorders26/55
HemoglobinBlood and lymphatic system disorders25/55
AnorexiaMetabolism and nutrition disorders24/55

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Single Arm
<=18 years0
Between 18 and 65 years37
>=65 years18
Age, Continuous
Age, Continuous(years)Single Arm
Mean60.9 ± 8.6
Sex: Female, Male
Sex: Female, Male(Participants)Single Arm
Female26
Male29
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Single Arm
Hispanic or Latino0
Not Hispanic or Latino55
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Single Arm
American Indian or Alaska Native0
Asian2
Native Hawaiian or Other Pacific Islander0
Black or African American6
White47
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)Single Arm
United States55
08

Study locations

1 site
  • Abramson Cancer Center of the University of Pennsylvania
    Philadelphia, Pennsylvania 19104-4283, United States
09

References and documents

Publications

  • Rengan R, Mick R, Pryma DA, Lin LL, Christodouleas J, Plastaras JP, Simone CB 2nd, Gupta AK, Evans TL, Stevenson JP, Langer CJ, Kucharczuk J, Friedberg J, Lam S, Patsch D, Hahn SM, Maity A. Clinical Outcomes of the HIV Protease Inhibitor Nelfinavir With Concurrent Chemoradiotherapy for Unresectable Stage IIIA/IIIB Non-Small Cell Lung Cancer: A Phase 1/2 Trial. JAMA Oncol. 2019 Oct 1;5(10):1464-1472. doi: 10.1001/jamaoncol.2019.2095. PubMed 31436839 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 24, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00589056
Lead sponsor
Abramson Cancer Center at Penn Medicine
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Jan 9, 2008
Start date
Jun 2007
Primary completion
Mar 2012
Completion
Mar 2012
Results posted
Apr 24, 2020
Last update
Apr 24, 2020

Study contacts

Amit Maity
principal investigator · Abramson Cancer Center at Penn Medicine

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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