Stereotactic Body Radiation With Nelfinavir for Oligometastases

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Completed
• CT.gov ID: NCT01728779
• Collaborator: (none)
• Enrollment: 38
• Location: 1
• Arm: 1
• Actual Duration (Months): 82.8
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Patients with metastatic lesions of the lung, liver, or bone will be candidates for treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment.

Condition or Disease	Intervention/Treatment	Phase
Oligometastases	Drug: Nelfinavir; Radiation: Stereotactic Body Radiation (SBRT)	Phase 2

Detailed Description

The use of radiation therapy to treat metastatic tumors is well established and promising data are emerging with the use of SBRT for metastatic disease. However, the use of a single large fraction concurrent with a radiosensitizer as is being proposed is not of proven benefit. This investigation aims to confirm the safety and efficacy for SBRT used concurrently with a radiosensitizer in the setting of oligometastatic disease. The dose selected has been chosen with the belief that it is safe and effective based on prior experience with SBRT of lung cancer, pancreatic cancer and brain radiosurgery. All patients will be treated with a single fraction (per lesion site), targeted to the lesion concurrently with the radiosensitizer Nelfinavir.

On the basis of this preclinical evidence, we propose a phase II study of Nelfinavir combined with SBRT in patients with oligometastatic disease. Because the standard dose of Nelfinavir for HIV patients is known to be safe and does inhibit the phosphorylation of Akt and decrease tumor hypoxia, we propose to study this in conjunction with a 15 Gy dose of SBRT. Experience with single-fraction pulmonary and pancreas SBRT provides a useful dose for this trial. With published data establishing the relative safety of large single-fraction SBRT to the lungs and pancreas, we have decided to proceed to determine the safety of 15 Gy SBRT concurrently with the radiosensitizer Nelfinavir. Once this is established, we propose to continue to enroll more patients to the study at this dose to determine the efficacy of this type of therapy.

The proposed study represents an informed estimate based on current knowledge of SBRT doses and those administered in currently approved image-guided protocols (brain, base of skull, cervico-thoracic spine, pancreas and liver). This study will refine the current understanding of single fraction radiation tolerance for normal tissues, thereby making it possible to treat future patients more safely and aggressively.

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Single-Arm Phase II Study of Stereotactic Body Radiation Therapy Concurrent With Nelfinavir for Oligometastases
• Actual Study Start Date: Jan 8, 2014
• Actual Primary Completion Date: Mar 1, 2020
• Actual Study Completion Date: Dec 1, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT) Patients with metastatic lesions of the lung, liver, or bone will be candidates for treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment.

Drug: Nelfinavir; Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days.; Other Names: Viracept ; Radiation: Stereotactic Body Radiation (SBRT); 15 Gy dose (per lesion site) of SBRT will be administered; Other Names: Stereotactic Body Radiation SBRT

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Freedom From Local Progression (FFLP) [6 months]

   To determine the 6-month Freedom From Local Progression rate (measured as a percentage of participants) in participants treated with radiosensitizer nelfinavir used concurrently with 15 Gy of stereotactic body radiation therapy (SBRT) delivered in 1 fraction in patients with oligometastatic disease. FFLP is defined as the percent of participants who were free from progression at the 6 month time point.

Secondary Outcome Measures

1. Total Number of Adverse Events Experienced by Participants [1 year]

   To assess the toxicity of the radiosensitizer Nelfinavir used concurrently with 15 Gy of stereotactic body radiation therapy (SBRT) delivered in 1 fraction (per lesion site) in patients with oligometastatic disease. Toxicity is assessed by the total number of adverse events based on Common Terminology Criteria for Adverse Events (CTCAE).

2. Percent of Lesions With Local Control at 6 Months Post-treatment [6 months]

   To determine percent of lesions with local control at 6-months after SBRT delivered to a dose of 15 Gy in 1 fraction (per lesion site) combined with nelfinavir in patients with oligometastatic disease.

3. Participants' Clinical Progress While in Follow-up in Terms of Survival [18 months]

   To assess the long-term clinical outcomes of this patient population after completion of SBRT in combination with Nelfinavir by determining the percentage of participants with Overall Survival (OS), Freedom From Distant Metastasis (FFDM) and the Progression-Free Survival (PFS).

4. Quality of Life After Completion of Treatment [3 years]

   To assess quality of life following completion of SBRT in combination with nelfinavir

5. Phospho/ Akt Levels With Respect to Lesion Response [3 months]

   Assess phospho-Akt protein in study participants to determine whether there is a correlation between the level protein and improved lesion response rate.

Eligibility Criteria

Criteria

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

Inclusion Criteria

• Patient's tumor(s) to be treated is(are) ≤ 5.0 cm or ≤250 cm3

• Patient must have metastasis at one or more of the following sites: bone, liver, lymph node and/or lung. No more than five lesions will be treated.

• Histological confirmation of malignancy (primary or metastatic tumor).

• Patient may have any prior therapy allowed aside from having had prior radiotherapy to the treatment site (see exclusion criteria 5.2.3).

• Patient must be ≥ 18 years of age.

• Patient must have a life expectancy ≥ 9 months.

• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

• Patient must have normal organ and marrow function.

• Patient must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study

• Patients receiving any other investigational agents

• Patient who has had any prior radiotherapy to the treatment site(s)

• Patients taking drugs that are contraindicated with nelfinavir, including any of the following:

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

• Women of child bearing potential who refuse to take a pregnancy test prior to treatment

• Participation in another concurrent treatment protocol while being treated on this protocol and through to 3 months after treatment on this protocol has ended

• Pregnant women

• Inability to understand the informed consent document

• Inability to sign the informed consent document

• Poor liver function suggestive of cirrhosis or steatohepatitis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Investigators

• Principal Investigator: Phuoc Tran, M.D., The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 19, 2020

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT01728779
• Other Study ID Numbers: J12137; NA_00069585
• First Posted: Nov 20, 2012
• Last Update Posted: Jul 12, 2021
• Last Verified: Jun 1, 2021

• Additional relevant MeSH terms: Nelfinavir

Study Results

Participant Flow

Recruitment Details	A total of 38 patients were accrued between January 2014 and December 2015 with one who withdrew consent and 37 were included in the analysis.

Arm/Group Title	Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	Patients with metastatic lesions of the lung, liver, or bone will be candidates for treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment. Nelfinavir: Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days. Stereotactic Body Radiation (SBRT): 15 Gy dose (per lesion site) of SBRT will be administered
Period Title: Overall Study
STARTED	38
COMPLETED	37
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	Patients with metastatic lesions of the lung, liver, or bone will be candidates for treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment. Nelfinavir: Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days. Stereotactic Body Radiation (SBRT): 15 Gy dose (per lesion site) of SBRT will be administered
Overall Participants	37
Age, Customized (years) [Median (Full Range) ]
Median (Full Range) [years]	65
Sex: Female, Male (Count of Participants)
Female	14 37.8%
Male	23 62.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 5.4%
Not Hispanic or Latino	35 94.6%
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	5 13.5%
White	32 86.5%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	37 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Freedom From Local Progression (FFLP)
Description	To determine the 6-month Freedom From Local Progression rate (measured as a percentage of participants) in participants treated with radiosensitizer nelfinavir used concurrently with 15 Gy of stereotactic body radiation therapy (SBRT) delivered in 1 fraction in patients with oligometastatic disease. FFLP is defined as the percent of participants who were free from progression at the 6 month time point.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	Patients with metastatic lesions of the lung, liver, or bone will be candidates for treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment. Nelfinavir: Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days. Stereotactic Body Radiation (SBRT): 15 Gy dose (per lesion site) of SBRT will be administered
Measure Participants	37
Number (95% Confidence Interval) [percentage of participants]	78.4 211.9%

2. Secondary Outcome

Title	Total Number of Adverse Events Experienced by Participants
Description	To assess the toxicity of the radiosensitizer Nelfinavir used concurrently with 15 Gy of stereotactic body radiation therapy (SBRT) delivered in 1 fraction (per lesion site) in patients with oligometastatic disease. Toxicity is assessed by the total number of adverse events based on Common Terminology Criteria for Adverse Events (CTCAE).
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	Patients with metastatic lesions of the lung, liver, or bone will be candidates for treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment. Nelfinavir: Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days. Stereotactic Body Radiation (SBRT): 15 Gy dose (per lesion site) of SBRT will be administered
Measure Participants	37
Anorexia	20
Anxiety	17
Cough	25
Agitation	3
Alanine Amino Trans increased	3
Alkaline Phosphatase increased	4
Alopecia	8
ALT Increase	3
Anemia	23
Apnea	3
Aspartate Amino Trans increased	2
Ataxia	1
Bilirubin Increased	3
Bloating	6
Bronchial Infection	1
Bruising	7
Chills	6
Colonic obstruction	1
Concentration Impairment	7
Conjunctivitis	2
Constipation	18
Creatinine increased	1
Cytokine Release Syndrome	1
Dehydration	4
Depression	15
Dermatitis	1
Diarrhea	31
Dizziness	11
Dry Mouth	14
Dyspepsia	13
Dyspnea	25
Edema	21
Esophageal pain	3
Esophagitis	5
Fatigue	32
Fecal Incontinence	4
Fever	1
Gastritis	3
Headache	12
Hearing Loss	1
Hematuria	3
Hemaglobin Increased	3
Hemorrhoids	12
Hiccups	2
Hot Flashes	4
Hyperglycemia	32
Hyperkalemia	4
Hypernatremia	1
Hypertension	1
Hypoglycemia	2
Hypokalemia	2
Hyponatremia	1
Hypoxia	1
Insomnia	1
Lymphocyte absolute decreased	22
Malaise	2
Nausea	23
Neuralgia	12
White blood cells decreased	22
Weight Loss	10
Weight Gain	15
Vomitting	10
Urticaria	2
Urinary Incontinence	25
Urinary Frequency	2
Tremor	3
Toothache	2
Stomatitis	2
Stomach Pain	11
Oral mucositis	3
Perineal Pain	1
Periodontal Disease	1
Platelet count decreased	13
Proctitis	2
Pruritis	9
Radiation Recall Rctn	3
Rash	2
Skin Infection	1
Short term memory impairment	1

3. Secondary Outcome

Title	Percent of Lesions With Local Control at 6 Months Post-treatment
Description	To determine percent of lesions with local control at 6-months after SBRT delivered to a dose of 15 Gy in 1 fraction (per lesion site) combined with nelfinavir in patients with oligometastatic disease.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	Patients with metastatic lesions of the lung, liver, or bone will be candidates for treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment. Nelfinavir: Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days. Stereotactic Body Radiation (SBRT): 15 Gy dose (per lesion site) of SBRT will be administered
Measure Participants	37
Measure Lesions	68
Number (95% Confidence Interval) [percentage of lesions]	76.5

4. Secondary Outcome

Title	Participants' Clinical Progress While in Follow-up in Terms of Survival
Description	To assess the long-term clinical outcomes of this patient population after completion of SBRT in combination with Nelfinavir by determining the percentage of participants with Overall Survival (OS), Freedom From Distant Metastasis (FFDM) and the Progression-Free Survival (PFS).
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	Patients with metastatic lesions of the lung, liver, or bone will be candidates for treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment. Nelfinavir: Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days. Stereotactic Body Radiation (SBRT): 15 Gy dose (per lesion site) of SBRT will be administered
Measure Participants	37
Overall Survival	90.7 245.1%
Freedom From Distant Metastasis	62.4 168.6%
Progression-Free Survival	57.6 155.7%

5. Secondary Outcome

Title	Quality of Life After Completion of Treatment
Description	To assess quality of life following completion of SBRT in combination with nelfinavir
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome measure.

Arm/Group Title	Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	Patients with metastatic lesions of the lung, liver, or bone will be candidates for treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment. Nelfinavir: Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days. Stereotactic Body Radiation (SBRT): 15 Gy dose (per lesion site) of SBRT will be administered
Measure Participants	0

6. Secondary Outcome

Title	Phospho/ Akt Levels With Respect to Lesion Response
Description	Assess phospho-Akt protein in study participants to determine whether there is a correlation between the level protein and improved lesion response rate.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome measure.

Arm/Group Title	Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	Patients with metastatic lesions of the lung, liver, or bone will be candidates for treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment. Nelfinavir: Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days. Stereotactic Body Radiation (SBRT): 15 Gy dose (per lesion site) of SBRT will be administered
Measure Participants	0

Adverse Events

Time Frame	Up to 36 months.
Adverse Event Reporting Description	All AEs were recorded throughout the study, however there were only 5 grade 3 adverse events in three patients as defined by CTCAE.
Arm/Group Title	Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)
Arm/Group Description	Patients with metastatic lesions of the lung, liver, or bone will be candidates for treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment. Nelfinavir: Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days. Stereotactic Body Radiation (SBRT): 15 Gy dose (per lesion site) of SBRT will be administered
All Cause Mortality
	Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)
	Affected / at Risk (%)	# Events
Total	3/37 (8.1%)
Serious Adverse Events
	Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)
	Affected / at Risk (%)	# Events
Total	3/37 (8.1%)
Gastrointestinal disorders
Nausea	1/37 (2.7%)	1
Anorexia	1/37 (2.7%)	1
Weight Loss	1/37 (2.7%)	1
Psychiatric disorders
Anxiety	1/37 (2.7%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/37 (2.7%)	1
Other (Not Including Serious) Adverse Events
	Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)
	Affected / at Risk (%)	# Events
Total	37/37 (100%)
Blood and lymphatic system disorders
Anemia	22/37 (59.5%)	22
Hyperkalemia	4/37 (10.8%)	4
Lymphocyte Absolute Increase	37/37 (100%)	37
WBC Decrease	22/37 (59.5%)	22
Platelet Count Decrease	13/37 (35.1%)	13
Endocrine disorders
Hot Flashes	4/37 (10.8%)	4
Hyperglycemia	32/37 (86.5%)	32
Gastrointestinal disorders
Bloating	6/37 (16.2%)	6
Constipation	18/37 (48.6%)	18
Diarrhea	36/37 (97.3%)	36
Dyspepsia	13/37 (35.1%)	13
Fecal Incontinence	4/37 (10.8%)	4
Hemmorhoids	12/37 (32.4%)	12
Nausea	22/37 (59.5%)	22
Vomitting	10/37 (27%)	10
General disorders
Alopecia	8/37 (21.6%)	8
Bruising	7/37 (18.9%)	7
Chills	6/37 (16.2%)	6
Dehydration	4/37 (10.8%)	4
Dry mouth	14/37 (37.8%)	14
Dyspenea	25/37 (67.6%)	25
Edema	21/37 (56.8%)	21
Fatigue	37/37 (100%)	37
Weight Loss	9/37 (24.3%)	9
Weight Increase	15/37 (40.5%)	15
Stomach Pain	11/37 (29.7%)	11
Pruritis	9/37 (24.3%)	9
Nervous system disorders
Concentration impairment	7/37 (18.9%)	7
Dizziness	11/37 (29.7%)	11
Headache	12/37 (32.4%)	12
Neuralgia	12/37 (32.4%)	12
Psychiatric disorders
Anorexia	19/37 (51.4%)	19
Anxiety	16/37 (43.2%)	16
Depression	15/37 (40.5%)	15
Renal and urinary disorders
Bilirubin	9/37 (24.3%)	9
Urinary Incontinence	25/37 (67.6%)	25
Respiratory, thoracic and mediastinal disorders
cough	24/37 (64.9%)	24
Esophogitis	5/37 (13.5%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.