Proton Beam Radiation With Concurrent Chemotherapy and Nelfinavir for Inoperable Stage III Non Small Cell Lung Cancer (NSCLC)

• Sponsor: Abramson Cancer Center of the University of Pennsylvania (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01108666
• Collaborator: (none)
• Enrollment: 7
• Location: 1
• Arm: 1
• Duration (Months): 105
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Seventy two patients are being asked to take part in this research study because they have been diagnosed with Stage IIIA or IIIB non-small cell lung cancer (NSCLC). This study is being done to determine the highest safe dose of proton beam radiotherapy and/or study drug (called Nelfinavir) that can be given with concurrent chemoradiotherapy to patients with cancer without causing bad side effects; and to develop biomarker for clinical outcome. This study will be done in two phases. In the first phase, feasibility will be established. We will follow patients treatment courses and record side effects at the standard proton radiation dose that can be given together with Cisplatinum + Etoposide or Carboplatin + Paclitaxel. In the second phase, we will see if it is possible to increase the total proton radiation dose or study drug without increasing the number of bad side effects while treated together with chemotherapy drugs.

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer	Drug: Nelfinavir	Phase 2

Detailed Description

Overall objectives:

1. Determine MTD of proton beam radiotherapy with concurrent cisplatin and etoposide for stage III NSCLC.

2. Determine MTD of proton beam radiotherapy with concurrent carboplatin and paclitaxel for stage III NSCLC in non-cisplatin candidates.

3. Determine MTD of Nelfinavir with concurrent chemoradiotherapy for stage III NSCLC at RPTD of proton beam radiotherapy.

4. Develop biomarker for clinical outcome with concurrent chemoradiotherapy in stage III NSCLC.

5. To determine clinical efficacy, as defined by metabolic response, sites of recurrence (e.g., local, regional, distant) and progression-free and overall survival.

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I Dose Escalation Trial of Proton Beam Radiotherapy With Concurrent Chemotherapy and Nelfinavir for Inoperable Stage III NSCLC
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Jul 1, 2018
• Actual Study Completion Date: Dec 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Proton RT and Nelfinavir	Drug: Nelfinavir; Two dose levels of Nelfinavir will be evaluated in each concurrent chemotherapy group (carboplatin/paclitaxel and cisplatin/etoposide) at the RPTD does of proton beam radiotherapy: 625 and 1250 mg PO bid.

Outcome Measures

Primary Outcome Measures

1. Feasibility of Proton Radiation [10 days]

   Ability to successfully plan proton plans

2. Acute Toxicity (or Dose Limiting Toxicity) [14 days]

   Dose limiting toxicities of grade 3 or higher per CTCAE 4.0

3. Late Toxicity [5 years]

   Late toxicities graded according to the RTOG/EORTC late morbidity scale

Secondary Outcome Measures

1. Clinical Efficacy [One year]

   Defined as metabolic response (complete, partial or less than partial) based on PET/CT imaging. Patients are followed for disease recurrence and site (local, regional, distant). Progression-free and overall survival are defined as from start of treatment to first documented recurrence (for PFS), date of death or last patient contact alive.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Histologically confirmed diagnosis of NSCLC.

2. Stage IIIA or IIIB NSCLC.

3. Patients must have no evidence of metastatic disease based on routine imaging.

4. Patients must have a Karnofsky Performance Status of 60.

5. Age 18 and older.

6. Patients must be able to provide informed consent.

7. Adequate bone marrow function (i.e. WBC larger than or equal to 4000/mm3, platelets larger than or equal to 100,000 mm3).

8. Adequate renal function for cisplatin or carboplatin as determined by the medical oncologist: Usually Calculated creatinine clearance (CrCl) larger than or equal to 45 mL/min or serum creatinine level smaller than or equal to1.5 x institutional ULN.

9. Patients must have bilirubin 1.5 mg/dl.

10. Women of child-bearing potential as long as she agrees to use a recognized method of birth control (e.g. oral contraceptive, IUD, condoms or other barrier methods etc).

11. Hysterectomy or menopause must be clinically documented.

Exclusion Criteria:

1. Prior or simultaneous malignancies within the past two years (other than cutaneous squamous or basal cell carcinoma or melanoma in situ).

2. Pregnant women, women planning to become pregnant and women that are nursing.

3. Actively being treated on any other research study.

4. For the Nelfinavir phase of the trial only: Patients who are taking Antiarrhythmics (amiodarone, quinidine), Antimycobacterial (rifampin), Ergot Derivatives (dihydroergotamine, ergonovine, ergotamine, ethylergonovine), Herbal Products (St. John's wort/ hypericum perforatum), HMG-CoA Reductase Inhibitors (lovastatin, simvastatin), Neuroleptic (pimozide), Proton Pump Inhibitors, or Sedative/ Hypnotics (midazolam, triazolam). Note: Patients with the following conditions are deemed unsuitable for cisplatin-based chemotherapy (and will be treated with carboplatin): (a) Hearing impairment/ peripheral neuropathy Grade 1 or less at baseline (b) Symptomatic/uncontrolled congestive heart failure (unable to tolerate volume load with pre- and post-cisplatin hydration)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Abramson Cancer Center of the University of Pennsylvania

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 6, 2016

More Information

Publications

None provided.

• Responsible Party: Abramson Cancer Center of the University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT01108666
• Other Study ID Numbers: UPCC 01510
• First Posted: Apr 22, 2010
• Last Update Posted: Jul 7, 2021
• Last Verified: Jul 1, 2021

• Keywords provided by Abramson Cancer Center of the University of Pennsylvania: Stage IIIA or IIIB NSCLC
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Nelfinavir

Study Results

Participant Flow

Arm/Group Title	Proton RT and Nelfinavir
Arm/Group Description	Nelfinavir: Two dose levels of Nelfinavir will be evaluated in each concurrent chemotherapy group (carboplatin/paclitaxel and cisplatin/etoposide) at the RPTD does of proton beam radiotherapy: 625 and 1250 mg PO bid.
Period Title: Overall Study
STARTED	7
COMPLETED	7
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Proton RT and Nelfinavir
Arm/Group Description	Nelfinavir: Two dose levels of Nelfinavir will be evaluated in each concurrent chemotherapy group (carboplatin/paclitaxel and cisplatin/etoposide) at the RPTD does of proton beam radiotherapy: 625 and 1250 mg PO bid.
Overall Participants	7
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 28.6%
>=65 years	5 71.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.11 (9.75)
Sex: Female, Male (Count of Participants)
Female	3 42.9%
Male	4 57.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	7 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 14.3%
White	6 85.7%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	7 100%

Outcome Measures

1. Primary Outcome

Title	Feasibility of Proton Radiation
Description	Ability to successfully plan proton plans
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

The PI has left the institution and despite all possible efforts is not able to be contacted, data are not available to be reported.

Arm/Group Title	Proton RT and Nelfinavir
Arm/Group Description	Nelfinavir: Two dose levels of Nelfinavir will be evaluated in each concurrent chemotherapy group (carboplatin/paclitaxel and cisplatin/etoposide) at the RPTD does of proton beam radiotherapy: 625 and 1250 mg PO bid.
Measure Participants	0

2. Primary Outcome

Title	Acute Toxicity (or Dose Limiting Toxicity)
Description	Dose limiting toxicities of grade 3 or higher per CTCAE 4.0
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

The PI has left the institution and cannot be contacted despite all possible efforts, data are not available to be reported.

Arm/Group Title	Proton RT and Nelfinavir
Arm/Group Description	Nelfinavir: Two dose levels of Nelfinavir will be evaluated in each concurrent chemotherapy group (carboplatin/paclitaxel and cisplatin/etoposide) at the RPTD does of proton beam radiotherapy: 625 and 1250 mg PO bid.
Measure Participants	0

3. Primary Outcome

Title	Late Toxicity
Description	Late toxicities graded according to the RTOG/EORTC late morbidity scale
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

Despite all possible efforts to contact the PI/study team members, no data are available to be reported

Arm/Group Title	Proton RT and Nelfinavir
Arm/Group Description	Nelfinavir: Two dose levels of Nelfinavir will be evaluated in each concurrent chemotherapy group (carboplatin/paclitaxel and cisplatin/etoposide) at the RPTD does of proton beam radiotherapy: 625 and 1250 mg PO bid.
Measure Participants	0

4. Secondary Outcome

Title	Clinical Efficacy
Description	Defined as metabolic response (complete, partial or less than partial) based on PET/CT imaging. Patients are followed for disease recurrence and site (local, regional, distant). Progression-free and overall survival are defined as from start of treatment to first documented recurrence (for PFS), date of death or last patient contact alive.
Time Frame	One year

Outcome Measure Data

Analysis Population Description

The PI has left the institution and cannot be contacted despite all possible efforts, data are not available to be reported.

Arm/Group Title	Proton RT and Nelfinavir
Arm/Group Description	Nelfinavir: Two dose levels of Nelfinavir will be evaluated in each concurrent chemotherapy group (carboplatin/paclitaxel and cisplatin/etoposide) at the RPTD does of proton beam radiotherapy: 625 and 1250 mg PO bid.
Measure Participants	0

Adverse Events

Time Frame	10 days
Adverse Event Reporting Description	Despite all possible efforts to contact the PI/study, data per dose-level are not available to be reported
Arm/Group Title	Proton RT and Nelfinavir
Arm/Group Description	Nelfinavir: Two dose levels of Nelfinavir will be evaluated in each concurrent chemotherapy group (carboplatin/paclitaxel and cisplatin/etoposide) at the RPTD does of proton beam radiotherapy: 625 and 1250 mg PO bid.
All Cause Mortality
	Proton RT and Nelfinavir
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Serious Adverse Events
	Proton RT and Nelfinavir
	Affected / at Risk (%)	# Events
Total	4/7 (57.1%)
Blood and lymphatic system disorders
Febrile neutropenia	1/7 (14.3%)
Hemolytic uremic syndrome	1/7 (14.3%)
Cardiac disorders
Hypotension	1/7 (14.3%)
Gastrointestinal disorders
Dysphagia	1/7 (14.3%)
Esophagitis	1/7 (14.3%)
Vomiting	1/7 (14.3%)
General disorders
Fever	1/7 (14.3%)
Infections and infestations
Lung infection	1/7 (14.3%)
Sepsis	1/7 (14.3%)
Investigations
Lymphocyte count decreased	2/7 (28.6%)
Platelet count decreased	1/7 (14.3%)
White blood cell decreased	1/7 (14.3%)
Metabolism and nutrition disorders
Dehydration	1/7 (14.3%)
Renal and urinary disorders
Renal failure	1/7 (14.3%)
Respiratory, thoracic and mediastinal disorders
Aspiration	2/7 (28.6%)
Bronchial fistula	1/7 (14.3%)
Pneumothorax	1/7 (14.3%)
Respiratory failure	1/7 (14.3%)
Other (Not Including Serious) Adverse Events
	Proton RT and Nelfinavir
	Affected / at Risk (%)	# Events
Total	6/7 (85.7%)
Blood and lymphatic system disorders
Anemia	5/7 (71.4%)
Cardiac disorders
Hypotension	1/7 (14.3%)
Ear and labyrinth disorders
Other Ear and labyrinth disorders	1/7 (14.3%)
Gastrointestinal disorders
Constipation	2/7 (28.6%)
Diarrhea	3/7 (42.9%)
Dyspepsia	2/7 (28.6%)
Dysphagia	4/7 (57.1%)
Esophageal pain	2/7 (28.6%)
Esophagitis	4/7 (57.1%)
Gastroparesis	1/7 (14.3%)
Nausea	4/7 (57.1%)
Oral dysesthesia	1/7 (14.3%)
Vomiting	3/7 (42.9%)
General disorders
Fatigue	5/7 (71.4%)
Fever	1/7 (14.3%)
Non-cardiac chest pain	1/7 (14.3%)
Pharyngolaryngeal pain	1/7 (14.3%)
Immune system disorders
Alopecia	1/7 (14.3%)
Infections and infestations
Esophageal infection	1/7 (14.3%)
Lung infection	3/7 (42.9%)
Mucosal infection	1/7 (14.3%)
Injury, poisoning and procedural complications
Dermatitis radiation	4/7 (57.1%)
Fall	2/7 (28.6%)
Investigations
Alanine aminotransferase increased	1/7 (14.3%)
Alkaline phosphatase increased	1/7 (14.3%)
Aspartate aminotransferase increased	2/7 (28.6%)
Blood bilirubin increased	2/7 (28.6%)
Creatinine increased	2/7 (28.6%)
Lymphocyte count decreased	4/7 (57.1%)
Neutrophil count decreased	2/7 (28.6%)
Platelet count decreased	3/7 (42.9%)
Weight gain	1/7 (14.3%)
Weight loss	2/7 (28.6%)
White blood cell decreased	5/7 (71.4%)
Metabolism and nutrition disorders
Anorexia	2/7 (28.6%)
Dehydration	4/7 (57.1%)
Hyperglycemia	4/7 (57.1%)
Hyperkalemia	1/7 (14.3%)
Hypermagnesemia	1/7 (14.3%)
Hypernatremia	1/7 (14.3%)
Hypoalbuminemia	4/7 (57.1%)
Hypocalcemia	4/7 (57.1%)
Hypoglycemia	2/7 (28.6%)
Hypokalemia	4/7 (57.1%)
Hypomagnesemia	4/7 (57.1%)
Hyponatremia	4/7 (57.1%)
Musculoskeletal and connective tissue disorders
Myalgia	1/7 (14.3%)
Nervous system disorders
Dizziness	1/7 (14.3%)
Headache	1/7 (14.3%)
Peripheral motor neuropathy	1/7 (14.3%)
Somnolence	1/7 (14.3%)
Psychiatric disorders
Anxiety	1/7 (14.3%)
Depression	1/7 (14.3%)
Insomnia	2/7 (28.6%)
Suicidal ideation	1/7 (14.3%)
Renal and urinary disorders
Urinary tract pain	1/7 (14.3%)
Reproductive system and breast disorders
Epistaxis	2/7 (28.6%)
Respiratory, thoracic and mediastinal disorders
Cough	1/7 (14.3%)
Dyspnea	3/7 (42.9%)
Hiccups	2/7 (28.6%)
Hoarseness	3/7 (42.9%)
Pleuritic pain	1/7 (14.3%)
Pneumonitis	1/7 (14.3%)
Sore throat	1/7 (14.3%)
Skin and subcutaneous tissue disorders
Pruritus	1/7 (14.3%)

Limitations/Caveats

[Not Specified]

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.