Trial Outcomes & Findings for A Phase 2 Clinical Trial of the Safety and Effects of IRX-2 in Treating Patients With Operable Head and Neck Cancer (NCT NCT00210470)

NCT ID: NCT00210470

Last Updated: 2020-12-11

Results Overview

The frequency of all Adverse Events (greater than 5%) is reported. All Serious Adverse Events were described.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 27 participants
• Primary outcome timeframe: Enrollment through 30 days post-surgery
• Results posted on: 2020-12-11

Participant Flow

The first subject was enrolled July 2005 and the last subject visit was August 2009.

Pathologically confirmed (by histology) squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. No prior surgery, radiation therapy, or chemotherapy of this tumor other than biopsy or emergency procedure required for supportive care. No medical contraindications to surgical resection and reconstruction required.

Participant milestones

Measure	IRX-2 Regimen The IRX-2 regimen is the combination of a 2-week course of IRX-2 itself, an initial dose of cyclophosphamide, and a 3-week course of indomethacin and zinc supplementation.
Overall Study STARTED	27
Overall Study COMPLETED	27
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase 2 Clinical Trial of the Safety and Effects of IRX-2 in Treating Patients With Operable Head and Neck Cancer

Baseline characteristics by cohort

Measure	IRX-2 Regimen n=27 Participants The IRX-2 regimen is the combination of a 2-week course of IRX-2 itself, an initial dose of cyclophosphamide, and a 3-week course of indomethacin and zinc supplementation.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	24 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants
Age, Continuous	57.4 years STANDARD_DEVIATION 9.4 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants
Region of Enrollment United States	26 participants n=5 Participants
Region of Enrollment Mexico	1 participants n=5 Participants

PRIMARY outcome

Timeframe: Enrollment through 30 days post-surgery

Population: 27 participants were entered into study and treated. All participants were included in the safety analysis.

The frequency of all Adverse Events (greater than 5%) is reported. All Serious Adverse Events were described.

Outcome measures

Measure	IRX-2 Regimen n=27 Participants A 2-week course of IRX-2, an initial low dose of cyclophosphamide, and a 3-week course of indomethacin and zinc supplementation	Low Lymphocyte Infiltration Participants with low lymphocyte infiltration after treatment with the IRX-2 regimen
Number of Participants With Adverse Events and Serious Adverse Events Adverse Event: Injection Site Pain	6 Participants	—
Number of Participants With Adverse Events and Serious Adverse Events Adverse Event: Headache	8 Participants	—
Number of Participants With Adverse Events and Serious Adverse Events Adverse Event: Nausea	6 Participants	—
Number of Participants With Adverse Events and Serious Adverse Events Adverse Event: Constipation	4 Participants	—
Number of Participants With Adverse Events and Serious Adverse Events Adverse Event: Dizziness	4 Participants	—
Number of Participants With Adverse Events and Serious Adverse Events Adverse Event: Fatigue	3 Participants	—
Number of Participants With Adverse Events and Serious Adverse Events Adverse Event: Pneumonia Aspiration	3 Participants	—
Number of Participants With Adverse Events and Serious Adverse Events Adverse Event: Anaemia	3 Participants	—
Number of Participants With Adverse Events and Serious Adverse Events Adverse Event: Injection Site Discomfort	3 Participants	—
Number of Participants With Adverse Events and Serious Adverse Events Adverse Event: Myalgia	2 Participants	—
Number of Participants With Adverse Events and Serious Adverse Events Adverse Event: Contusion	2 Participants	—
Number of Participants With Adverse Events and Serious Adverse Events Adverse Event: Dry Mouth	2 Participants	—
Number of Participants With Adverse Events and Serious Adverse Events Adverse Event: Vomiting	2 Participants	—
Number of Participants With Adverse Events and Serious Adverse Events Additional AE Categories w lower frequency	4 Participants	—
Number of Participants With Adverse Events and Serious Adverse Events Serious Adverse Events	7 Participants	—

SECONDARY outcome

Timeframe: On approximately Day 21 (last day of treatment) prior to undergoing post-treatment surgery

Population: A total of 23 subjects who received the IRX-2 regimen were evaluated for tumor response based on the RECIST criteria

Number of participants with the specified percent change in size of target lesion is presented

Outcome measures

Measure	IRX-2 Regimen n=23 Participants A 2-week course of IRX-2, an initial low dose of cyclophosphamide, and a 3-week course of indomethacin and zinc supplementation	Low Lymphocyte Infiltration Participants with low lymphocyte infiltration after treatment with the IRX-2 regimen
Clinical and Histological Tumor Responses -20% to < -10%	4 Participants	—
Clinical and Histological Tumor Responses -10% to < 0%	7 Participants	—
Clinical and Histological Tumor Responses 0% to < 10%	9 Participants	—
Clinical and Histological Tumor Responses 10% to < 20%	1 Participants	—
Clinical and Histological Tumor Responses 20% to < 30%	0 Participants	—
Clinical and Histological Tumor Responses >= 30%	2 Participants	—

SECONDARY outcome

Timeframe: Following surgery and post-operative therapy (up to 39 days post surgery)

Population: Following surgery the median days spent in the hospital, intensive care unit and step down unit was determined for 26 subjects

Patient Tolerance of Surgery and Post-operative Adjuvant Therapy as measured by median days spent in the hospital, intensive care unit, and step down unit.

Outcome measures

Measure	IRX-2 Regimen n=26 Participants A 2-week course of IRX-2, an initial low dose of cyclophosphamide, and a 3-week course of indomethacin and zinc supplementation	Low Lymphocyte Infiltration Participants with low lymphocyte infiltration after treatment with the IRX-2 regimen
Patient Tolerance of Surgery and Post-operative Adjuvant Therapy; Median Days in hospital	8.5 days Interval 1.0 to 39.0	—
Patient Tolerance of Surgery and Post-operative Adjuvant Therapy; Median Days in intensive care unit	0.5 days Interval 0.0 to 17.0	—
Patient Tolerance of Surgery and Post-operative Adjuvant Therapy; Median Days in step-down unit	0.5 days Interval 0.0 to 22.0	—

SECONDARY outcome

Timeframe: At approx. 21 days, prior to surgery

Population: Skin response (erythema) was evaluated at Baseline and Day 21 on 26 subjects treated with IRX-2 Regimen

To assess measures of immune competence following administration of the IRX-2 regimen, including skin test reactivity.

Outcome measures

Measure	IRX-2 Regimen n=26 Participants A 2-week course of IRX-2, an initial low dose of cyclophosphamide, and a 3-week course of indomethacin and zinc supplementation	Low Lymphocyte Infiltration Participants with low lymphocyte infiltration after treatment with the IRX-2 regimen
Immune Competence as Measured by Skin Test Reactivity Positive at both Baseline and at Day 21 (%)	12 Participants	—
Immune Competence as Measured by Skin Test Reactivity Negative at both Baseline and Day 21 (%)	6 Participants	—
Immune Competence as Measured by Skin Test Reactivity Positive at Baseline and Negative Day 21 (%)	6 Participants	—
Immune Competence as Measured by Skin Test Reactivity Negative at Baseline and Positive at Day 21	2 Participants	—
Immune Competence as Measured by Skin Test Reactivity Induration at Day 21	3 Participants	—

SECONDARY outcome

Timeframe: Time from surgery to death or clinically apparent, biopsy confirmed recurrent or progressive disease after the completion of initial therapy, assessed up to 3 years; margins of resection positive for tumor will not be considered disease recurrence

Estimate disease-free survival (DFS) (time from surgery to death or clinically apparent, biopsy confirmed recurrent or progressive disease after the completion of initial therapy, assessed up to 3 years; margins of resection positive for tumor will not be considered disease recurrence).

Outcome measures

Measure	IRX-2 Regimen n=26 Participants A 2-week course of IRX-2, an initial low dose of cyclophosphamide, and a 3-week course of indomethacin and zinc supplementation	Low Lymphocyte Infiltration Participants with low lymphocyte infiltration after treatment with the IRX-2 regimen
Disease-free Survival 1-year disease free survival probability	0.721 DFS Probability	—
Disease-free Survival 2-year disease free survival probability	0.641 DFS Probability	—
Disease-free Survival 3-year disease free survival probability	0.620 DFS Probability	—

SECONDARY outcome

Timeframe: Time from surgery to death or confirmed recurrent or progressive disease, assessed up to 3 years

Estimate overall survival (OS) in patients receiving the IRX-2 regimen. IRX-2 is currently being studied in an on-going Phase 2b clinical trial in patients with newly diagnosed Stage II, III, and IVA squamous cell carcinoma of the oral cavity (INSPIRE)

Outcome measures

Measure	IRX-2 Regimen n=26 Participants A 2-week course of IRX-2, an initial low dose of cyclophosphamide, and a 3-week course of indomethacin and zinc supplementation	Low Lymphocyte Infiltration Participants with low lymphocyte infiltration after treatment with the IRX-2 regimen
Overall Survival Second Year (%)	73 percentage of subjects	—
Overall Survival First Year (%)	92 percentage of subjects	—
Overall Survival Third Year (%)	69 percentage of subjects	—

SECONDARY outcome

Timeframe: On approximately Day 21 (last day of treatment) prior to undergoing post-treatment surgery

Population: Number of patients with high lymphocyte infiltration (LI).

Immunologic response features were extracted and quantified using a VAS of 0-100 mm to provide for a more continuous variable than the 0-4+ scale that is often used to assess histological responses. The scoring was such that 100 represented the maximum for any sample and 0 represented the lack of any parameter of interest.

See publication of Berinstein, et al., 2012 for complete details.

Outcome measures

Measure	IRX-2 Regimen n=25 Participants A 2-week course of IRX-2, an initial low dose of cyclophosphamide, and a 3-week course of indomethacin and zinc supplementation	Low Lymphocyte Infiltration Participants with low lymphocyte infiltration after treatment with the IRX-2 regimen
Number of Participants With High Lymphocyte Infiltration (LI) According to the Visual Analog Scale (VAS)	18 participants with high LI (>34 mm) VAS	—

SECONDARY outcome

Timeframe: At time of surgery, after treatment with IRX-2 Regimen, assessed up to 5 years

After participants completed the IRX-2 regimen and the tumor resection was performed, tumor pathology was evaluated from tissue specimens obtained at tumor resection. Formalin-fixed, paraffin-embedded blocks, or unstained slides from the primary tumor were submitted to an independent pathology laboratory for hematoxylin and eosin staining, and evaluation of lymphocyte infiltration (LI). Participants were grouped into a "low LI" and "high LI" group based on the change in lymphocyte infiltration from the pretreatment tumor biopsy to the post-treatment tumor surgical resection. 5-year overall survival probabilities were then estimated (Kaplan-Meier) between the "low LI" and "high LI" groups

Outcome measures

Measure	IRX-2 Regimen n=13 Participants A 2-week course of IRX-2, an initial low dose of cyclophosphamide, and a 3-week course of indomethacin and zinc supplementation	Low Lymphocyte Infiltration n=12 Participants Participants with low lymphocyte infiltration after treatment with the IRX-2 regimen
Relationship Between Overall Survival (OS) and Immune Competence (Lymphocyte Infiltration, LI) in Participants With High LI and Low LI	0.80 5-Year OS Probability	0.50 5-Year OS Probability

Adverse Events

IRX-2 Regimen

Serious events: 7 serious events

Other events: 23 other events

Deaths: 10 deaths

Serious adverse events

Measure	IRX-2 Regimen n=27 participants at risk The IRX-2 regimen is the combination of a 2-week course of IRX-2 itself, an initial dose of cyclophosphamide, and a 3-week course of indomethacin and zinc supplementation.
Infections and infestations ASPIRATION PNEUMONIA	11.1% 3/27 • Number of events 3 • Primarily from the administration of cyclophosphamide to the time of surgery, except for Serious Adverse Events (reported up to 30 days after last dose of study medication)
Respiratory, thoracic and mediastinal disorders RESPIRATORY INFECTION	3.7% 1/27 • Number of events 2 • Primarily from the administration of cyclophosphamide to the time of surgery, except for Serious Adverse Events (reported up to 30 days after last dose of study medication)
Infections and infestations NECK ABSCESS	3.7% 1/27 • Number of events 1 • Primarily from the administration of cyclophosphamide to the time of surgery, except for Serious Adverse Events (reported up to 30 days after last dose of study medication)
Infections and infestations POSTOPERATIVE INFECTION	3.7% 1/27 • Number of events 1 • Primarily from the administration of cyclophosphamide to the time of surgery, except for Serious Adverse Events (reported up to 30 days after last dose of study medication)
General disorders ALCOHOL WITHDRAWAL	3.7% 1/27 • Number of events 1 • Primarily from the administration of cyclophosphamide to the time of surgery, except for Serious Adverse Events (reported up to 30 days after last dose of study medication)

Other adverse events

Measure	IRX-2 Regimen n=27 participants at risk The IRX-2 regimen is the combination of a 2-week course of IRX-2 itself, an initial dose of cyclophosphamide, and a 3-week course of indomethacin and zinc supplementation.
Gastrointestinal disorders CONSTIPATION	14.8% 4/27 • Number of events 4 • Primarily from the administration of cyclophosphamide to the time of surgery, except for Serious Adverse Events (reported up to 30 days after last dose of study medication)
General disorders DIZZINESS	14.8% 4/27 • Number of events 4 • Primarily from the administration of cyclophosphamide to the time of surgery, except for Serious Adverse Events (reported up to 30 days after last dose of study medication)
General disorders FATIGUE	11.1% 3/27 • Number of events 3 • Primarily from the administration of cyclophosphamide to the time of surgery, except for Serious Adverse Events (reported up to 30 days after last dose of study medication)
General disorders HEADACHE	29.6% 8/27 • Number of events 8 • Primarily from the administration of cyclophosphamide to the time of surgery, except for Serious Adverse Events (reported up to 30 days after last dose of study medication)
General disorders INJECTION SITE PAIN	22.2% 6/27 • Number of events 6 • Primarily from the administration of cyclophosphamide to the time of surgery, except for Serious Adverse Events (reported up to 30 days after last dose of study medication)
General disorders NAUSEA	22.2% 6/27 • Number of events 6 • Primarily from the administration of cyclophosphamide to the time of surgery, except for Serious Adverse Events (reported up to 30 days after last dose of study medication)
Respiratory, thoracic and mediastinal disorders PNEUMONIA ASPIRATION	11.1% 3/27 • Number of events 3 • Primarily from the administration of cyclophosphamide to the time of surgery, except for Serious Adverse Events (reported up to 30 days after last dose of study medication)
Gastrointestinal disorders DRY MOUTH	7.4% 2/27 • Number of events 2 • Primarily from the administration of cyclophosphamide to the time of surgery, except for Serious Adverse Events (reported up to 30 days after last dose of study medication)
Gastrointestinal disorders VOMITING	7.4% 2/27 • Number of events 2 • Primarily from the administration of cyclophosphamide to the time of surgery, except for Serious Adverse Events (reported up to 30 days after last dose of study medication)
Musculoskeletal and connective tissue disorders MYALGIA	7.4% 2/27 • Number of events 2 • Primarily from the administration of cyclophosphamide to the time of surgery, except for Serious Adverse Events (reported up to 30 days after last dose of study medication)
Injury, poisoning and procedural complications CONTUSION	7.4% 2/27 • Number of events 2 • Primarily from the administration of cyclophosphamide to the time of surgery, except for Serious Adverse Events (reported up to 30 days after last dose of study medication)
Blood and lymphatic system disorders ANAEMIA	11.1% 3/27 • Number of events 3 • Primarily from the administration of cyclophosphamide to the time of surgery, except for Serious Adverse Events (reported up to 30 days after last dose of study medication)
General disorders INJECTION SITE DISCOMFORT	7.4% 2/27 • Number of events 2 • Primarily from the administration of cyclophosphamide to the time of surgery, except for Serious Adverse Events (reported up to 30 days after last dose of study medication)

Additional Information

Gregory T. Wolf

University of Michigan Hospital

Email: gregwolf@umich.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60