Oral Mucositis
Conditions
Brief summary
To evaluate the safety and efficacy of SGX942 in patients receiving chemoradiation treatment for the treatment of head and neck cancer.
Interventions
DRUGSGX942
DRUGPlacebo
Sponsors
Soligenix
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Biopsy-proven non-metastatic squamous cell carcinoma of the mouth or oropharynx and is planned to receive a standard course of concomitant CRT. * Patients who have received surgery are eligible if surgery is performed within 6 weeks prior to study initiation. * Planned to receive standard cisplatin chemotherapy administered either weekly or every third week. * Must be able to read and understand informed consent * Adequate birth control methods for the duration of the study
Exclusion criteria
* Current mucositis. * Prior radiation to the head and neck. * Chemotherapy treatment within the previous 12 months. * Tumors of the lips, sinuses, salivary glands or nasopharynx. * Unknown primary tumor. * Stage 4c metastases. * Evidence of significant hepatic, hematologic, or immunologic disease. * Women who are pregnant or breast-feeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Severe Oral Mucositis (SOM) | 4 weeks after end of therapy | Duration of SOM was defined as the number of days from the onset of SOM until resolution of SOM. If the patient did not meet the requirements for resolution of SOM by the 1-month follow up visit, he/she was considered censored at the 1-month follow-up visit (or point of discontinuation of the study, if the patient had discontinued prior to the end of planned treatment). Patients who did not experience SOM were assigned a duration of 0.01. OM was evaluated using the published World Health Organization (WHO) OM grading scale that uses a scale of 0 to 4. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival | 12 months after end of therapy | — |
| Residual Severe Oral Mucositis (SOM) | 4 weeks after end of therapy | OM was evaluated using the published World Health Organization (WHO) OM grading scale that uses a scale of 0 to 4. SOM is defined as a WHO score of greater than or equal to 3. |
| Duration of Severe Oral Mucositis (SOM) | 4 weeks after end of therapy | OM was evaluated using the published World Health Organization (WHO) OM grading scale that uses a scale of 0 to 4. SOM is defined as a WHO score of greater than or equal to 3. |
| Incidence of Severe Oral Mucositis (SOM) in Patients Receiving Every 3rd Week Cisplatin | 4 weeks after end of therapy | — |
| Percent of Patients With RECIST 1.1 Classification of Complete Response | 4 weeks after end of therapy | The RECIST 1.1 scoring system evaluates both the defined (target) tumor, the non-target lesions, and the appearance of new lesions on radiologic scans as follows: Target Lesion : Complete Response (CR): All target lesions gone Partial Response (PR): \>30% decrease from Baseline Progressive Disease (PD): \>20% increase from smallest sum of longest diameter recorded since treatment started (best response) Stable Disease (SD): Neither PD nor PR Non-Target Lesion: Complete Response (CR): All non-target lesions gone,Tumor markers gone Stable Disease (SD): Persistence of ≥1 non-target lesion, Tumor marker level elevated Progressive Disease: Enlargement of non-target lesions |
| Duration of Severe Oral Mucositis (SOM) in Patients Receiving Every 3rd Week Cisplatin | 4 weeks after end of therapy | — |
| Incidence of Clinically Reported, Non-fungal Infections | 4 weeks after end of therapy | — |
Countries
United States
Participant flow
Pre-assignment details
Two patients were randomized but never received study drug and are excluded from the analyses
Participants by arm
| Arm | Count |
|---|---|
| Placebo | 42 |
| 1.5 mg/kg | 41 |
| 3.0 mg/kg | 3 |
| 6.0 mg/kg | 23 |
| Total | 109 |
Baseline characteristics
| Characteristic | Placebo | 1.5 mg/kg | 3.0 mg/kg | 6.0 mg/kg | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 10 Participants | 1 Participants | 3 Participants | 25 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 31 Participants | 2 Participants | 20 Participants | 84 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 0 Participants | 3 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 38 Participants | 3 Participants | 20 Participants | 101 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 5 Participants | 0 Participants | 2 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 38 Participants | 36 Participants | 3 Participants | 20 Participants | 97 Participants |
| Region of Enrollment United States | 42 participants | 41 participants | 3 participants | 23 participants | 109 participants |
| Sex: Female, Male Female | 9 Participants | 9 Participants | 2 Participants | 3 Participants | 23 Participants |
| Sex: Female, Male Male | 33 Participants | 32 Participants | 1 Participants | 20 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 8 / 43 | 3 / 41 | 0 / 3 | 4 / 24 |
| other Total, other adverse events | 41 / 41 | 42 / 42 | 3 / 3 | 23 / 23 |
| serious Total, serious adverse events | 25 / 41 | 25 / 42 | 1 / 3 | 16 / 23 |
Outcome results
Primary
Duration of Severe Oral Mucositis (SOM)
Duration of SOM was defined as the number of days from the onset of SOM until resolution of SOM. If the patient did not meet the requirements for resolution of SOM by the 1-month follow up visit, he/she was considered censored at the 1-month follow-up visit (or point of discontinuation of the study, if the patient had discontinued prior to the end of planned treatment). Patients who did not experience SOM were assigned a duration of 0.01. OM was evaluated using the published World Health Organization (WHO) OM grading scale that uses a scale of 0 to 4.
Time frame: 4 weeks after end of therapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Duration of Severe Oral Mucositis (SOM) | 18 days |
| 1.5 mg/kg | Duration of Severe Oral Mucositis (SOM) | 9 days |
| 3.0 mg/kg | Duration of Severe Oral Mucositis (SOM) | 14 days |
| 6.0 mg/kg | Duration of Severe Oral Mucositis (SOM) | 22 days |
Secondary
Duration of Severe Oral Mucositis (SOM)
OM was evaluated using the published World Health Organization (WHO) OM grading scale that uses a scale of 0 to 4. SOM is defined as a WHO score of greater than or equal to 3.
Time frame: 4 weeks after end of therapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Duration of Severe Oral Mucositis (SOM) | 35.5 WHO score * days |
| 1.5 mg/kg | Duration of Severe Oral Mucositis (SOM) | 21.8 WHO score * days |
| 3.0 mg/kg | Duration of Severe Oral Mucositis (SOM) | 33.0 WHO score * days |
| 6.0 mg/kg | Duration of Severe Oral Mucositis (SOM) | 46.5 WHO score * days |
Secondary
Duration of Severe Oral Mucositis (SOM) in Patients Receiving Every 3rd Week Cisplatin
Time frame: 4 weeks after end of therapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Duration of Severe Oral Mucositis (SOM) in Patients Receiving Every 3rd Week Cisplatin | 30 days |
| 1.5 mg/kg | Duration of Severe Oral Mucositis (SOM) in Patients Receiving Every 3rd Week Cisplatin | 10 days |
| 3.0 mg/kg | Duration of Severe Oral Mucositis (SOM) in Patients Receiving Every 3rd Week Cisplatin | 14 days |
| 6.0 mg/kg | Duration of Severe Oral Mucositis (SOM) in Patients Receiving Every 3rd Week Cisplatin | 17 days |
Secondary
Incidence of Clinically Reported, Non-fungal Infections
Time frame: 4 weeks after end of therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Incidence of Clinically Reported, Non-fungal Infections | 45 percentage of participants |
| 1.5 mg/kg | Incidence of Clinically Reported, Non-fungal Infections | 28 percentage of participants |
| 3.0 mg/kg | Incidence of Clinically Reported, Non-fungal Infections | 0 percentage of participants |
| 6.0 mg/kg | Incidence of Clinically Reported, Non-fungal Infections | 21 percentage of participants |
Secondary
Incidence of Severe Oral Mucositis (SOM) in Patients Receiving Every 3rd Week Cisplatin
Time frame: 4 weeks after end of therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Incidence of Severe Oral Mucositis (SOM) in Patients Receiving Every 3rd Week Cisplatin | 82 percentage of participants |
| 1.5 mg/kg | Incidence of Severe Oral Mucositis (SOM) in Patients Receiving Every 3rd Week Cisplatin | 67 percentage of participants |
| 3.0 mg/kg | Incidence of Severe Oral Mucositis (SOM) in Patients Receiving Every 3rd Week Cisplatin | 67 percentage of participants |
| 6.0 mg/kg | Incidence of Severe Oral Mucositis (SOM) in Patients Receiving Every 3rd Week Cisplatin | 80 percentage of participants |
Secondary
Percent of Patients With RECIST 1.1 Classification of Complete Response
The RECIST 1.1 scoring system evaluates both the defined (target) tumor, the non-target lesions, and the appearance of new lesions on radiologic scans as follows: Target Lesion : Complete Response (CR): All target lesions gone Partial Response (PR): \>30% decrease from Baseline Progressive Disease (PD): \>20% increase from smallest sum of longest diameter recorded since treatment started (best response) Stable Disease (SD): Neither PD nor PR Non-Target Lesion: Complete Response (CR): All non-target lesions gone,Tumor markers gone Stable Disease (SD): Persistence of ≥1 non-target lesion, Tumor marker level elevated Progressive Disease: Enlargement of non-target lesions
Time frame: 12 months after end of therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Patients With RECIST 1.1 Classification of Complete Response | 53 percentage of participants |
| 1.5 mg/kg | Percent of Patients With RECIST 1.1 Classification of Complete Response | 53 percentage of participants |
| 3.0 mg/kg | Percent of Patients With RECIST 1.1 Classification of Complete Response | 33 percentage of participants |
| 6.0 mg/kg | Percent of Patients With RECIST 1.1 Classification of Complete Response | 53 percentage of participants |
Secondary
Percent of Patients With RECIST 1.1 Classification of Complete Response
The RECIST 1.1 scoring system evaluates both the defined (target) tumor, the non-target lesions, and the appearance of new lesions on radiologic scans as follows: Target Lesion : Complete Response (CR): All target lesions gone Partial Response (PR): \>30% decrease from Baseline Progressive Disease (PD): \>20% increase from smallest sum of longest diameter recorded since treatment started (best response) Stable Disease (SD): Neither PD nor PR Non-Target Lesion: Complete Response (CR): All non-target lesions gone,Tumor markers gone Stable Disease (SD): Persistence of ≥1 non-target lesion, Tumor marker level elevated Progressive Disease: Enlargement of non-target lesions
Time frame: 4 weeks after end of therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Patients With RECIST 1.1 Classification of Complete Response | 39 percentage of participants |
| 1.5 mg/kg | Percent of Patients With RECIST 1.1 Classification of Complete Response | 47 percentage of participants |
| 3.0 mg/kg | Percent of Patients With RECIST 1.1 Classification of Complete Response | 33 percentage of participants |
| 6.0 mg/kg | Percent of Patients With RECIST 1.1 Classification of Complete Response | 21 percentage of participants |
Secondary
Residual Severe Oral Mucositis (SOM)
OM was evaluated using the published World Health Organization (WHO) OM grading scale that uses a scale of 0 to 4. SOM is defined as a WHO score of greater than or equal to 3.
Time frame: 4 weeks after end of therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Residual Severe Oral Mucositis (SOM) | 21 percentage of participants |
| 1.5 mg/kg | Residual Severe Oral Mucositis (SOM) | 6 percentage of participants |
| 3.0 mg/kg | Residual Severe Oral Mucositis (SOM) | 33 percentage of participants |
| 6.0 mg/kg | Residual Severe Oral Mucositis (SOM) | 16 percentage of participants |
Secondary
Survival
Time frame: 12 months after end of therapy
Population: Safety Population: all patients randomized who received at least 1 dose of study drug and were included in the dose group of the drug that they actually received instead of the drug dose they were randomized. 2 patients were randomized but never received drug and are excluded. 1 patient was randomized to placebo but received 1.5 mg/kg SGX942.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Survival | 81 percentage of participants |
| 1.5 mg/kg | Survival | 93 percentage of participants |
| 3.0 mg/kg | Survival | 100 percentage of participants |
| 6.0 mg/kg | Survival | 83 percentage of participants |