Advanced Cervical Adenocarcinoma, Advanced Cervical Adenosquamous Carcinoma, Advanced Cervical Squamous Cell Carcinoma, Advanced Vaginal Adenocarcinoma, Advanced Vaginal Adenosquamous Carcinoma, Advanced Vaginal Squamous Cell Carcinoma, Stage IB2 Cervical Cancer AJCC v6 and v7, Stage II Cervical Cancer AJCC v7, Stage II Vaginal Cancer AJCC v6 and v7, Stage III Vaginal Cancer AJCC v6 and v7, Stage IIIB Cervical Cancer AJCC v6 and v7, Stage IVA Cervical Cancer AJCC v6 and v7, Stage IVA Vaginal Cancer AJCC v6 and v7
Conditions
Brief summary
This phase I trial studies the side effects and best dose of triapine when given with radiation therapy and cisplatin in treating patients with stage IB2-IVA cervical or vaginal cancer. Triapine may stop the growth of cancer cells by blocking an enzyme needed for cell growth. Cisplatin is a drug used in chemotherapy that kills cancer cells by damaging their deoxyribonucleic acid (DNA) and stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Adding triapine to standard treatment with cisplatin and radiation therapy may kill more cancer cells.
Detailed description
PRIMARY OBJECTIVES: I. To determine the maximum tolerable dose (MTD) and recommended phase II dose (RP2D) of oral triapine when used in combination with cisplatin plus radiation therapy. II. To determine the oral bioavailability of triapine. III. To describe the pharmacokinetics (PK) of oral and intravenous triapine. SECONDARY OBJECTIVES: I. To determine whether the metabolic complete response (mCR) rate of oral triapine in combination with cisplatin chemoradiation using fludeoxyglucose F 18 (18F-FDG)-positron emission tomography (PET)/computed tomography (CT) at post-therapy (3-month) is at least 70%. II. To determine clinical overall response rate, progression-free survival, and overall survival. III. To determine the correlation of methemoglobin proportion (%) and triapine pharmacokinetic exposure. EXPLORATORY OBJECTIVE: I. To determine whether active human immunodeficiency virus (HIV) antiretroviral therapy impacts the antitumor activity of triapine. OUTLINE: This is a dose-escalation study of triapine. Patients undergo pelvic external beam radiation therapy (EBRT) or intensity modulated radiation therapy (IMRT) 5 days per week for 5 weeks (25 fractions) with a 3-day boost in week 6, and 1 or 2 applications of low dose rate (LDR) brachytherapy in week 6 or 5 fractions of high dose rate (HDR) brachytherapy at week 4 or 5. Patients also receive triapine intravenously (IV) over 120 minutes on day 1 and orally (PO) on days 2-5, 8-12, 15-19, 22-26, and 29-33 within 90 minutes after pelvic irradiation, and cisplatin IV over 60-120 minutes once weekly for 5 weeks (days 2, 9, 16, 23, and 30). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients may receive a 6th cycle of cisplatin IV during the parametrial boost or any make-up radiation treatment in a sixth week of external beam radiotherapy. Patients undergo the collection of blood samples on study and undergo magnetic resonance imaging (MRI) and FDG-PET/CT during follow-up.
Interventions
PROCEDUREBiospecimen Collection
Undergo collection of blood samples
RADIATIONBrachytherapy
Undergo LDR brachytherapy
DRUGCisplatin
Given IV
PROCEDUREComputed Tomography
Undergo FDG-PET/CT
RADIATIONExternal Beam Radiation Therapy
Undergo pelvic EBRT
OTHERFludeoxyglucose F-18
Undergo FDG-PET/CT
RADIATIONHigh-Dose Rate Brachytherapy
Undergo HDR brachytherapy
RADIATIONIntensity-Modulated Radiation Therapy
Undergo IMRT
PROCEDUREMagnetic Resonance Imaging
Undergo MRI
OTHERPharmacological Study
Correlative studies
PROCEDUREPositron Emission Tomography
Undergo FDG-PET/CT
DRUGTriapine
Given IV and PO
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient has a new, untreated histologic diagnosis of stage IB2 (\> 5 cm), II, IIIB, IIIC or IVA squamous, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix or stage II-IVA squamous, adenocarcinoma, or adenosquamous carcinoma of the vagina not amenable to curative surgical resection alone; the presence or absence of lymph node metastasis will be based on pre-therapy 18F-FDG PET/CT; the patient must be able to tolerate imaging requirements of an 18F-FDG PET/CT scan * Age \>= 18 years old * Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 * Life expectancy greater than 6 months * Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L * Platelets \>= 100 x 10\^9/L * Hemoglobin (Hgb) \>= 10.0 g/dL (blood transfusions to reach this amount are allowed) * Serum creatinine =\< 1.5 mg/dL to receive weekly cisplatin * If serum creatinine is between 1.5 and 1.9 mg/dL, patients are eligible for cisplatin if the estimated creatinine clearance (CCr) is \> 30 ml/min (for the purpose of estimating the CCr, the formula of Cockcroft and Gault for females should be used) * Total serum bilirubin =\< 1.5 x upper limit of normal (ULN) (in patients with known Gilbert syndrome, a total bilirubin =\< 3.0 x ULN, with direct bilirubin =\< 1.5 x ULN) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN * Able to take oral medication * Not pregnant and not breastfeeding; the effects of triapine on the developing human fetus are unknown; for this reason as well as because heterocyclic carboxaldehydethiosemicarbazones and radiation are known to be teratogenic, women of child-bearing potential and men must agree to use two forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; patient must have documented negative urine pregnancy test must be resulted within 7 days before initiating protocol therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with triapine, breastfeeding should be discontinued if the mother is treated with triapine; these potential risks may also apply to other agents used in this study * For HIV and hepatitis B/C (HEPB/C): * HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for the dose escalation portion of this trial; for those patients who are enrolled in the HIV positive (+) expansion cohort, they must be HIV infected and be on retroviral therapy with an undetectable viral load within 6 months of enrollment * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured; for patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load * Able to understand and willingness to sign a written informed consent document
Exclusion criteria
* Patient has had a prior invasive malignancy diagnosed within the last three years (except \[1\] non-melanoma skin cancer or \[2\] prior in situ carcinoma of the cervix) * Patients are excluded if they have received prior pelvic radiotherapy for any reason that would contribute radiation dose that would exceed tolerance of normal tissues at the discretion of the treating physician * Patients receiving any other investigational agents * Patients with known glucose-6-phosphate dehydrogenase deficiency (G6PD) are excluded due to an inability to administer the antidote for methemoglobinemia, methylene blue; pre-registration testing for G6PD is at the investigator's discretion and is not required for study enrollment * Patients who are taking any medication associated with methemoglobinemia; medication must be discontinued and must have a washout period of 4 halflives or 4 weeks, whichever is shorter * History of allergic reactions attributed to compounds of similar chemical or biologic composition to triapine or cisplatin * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection; symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia; known inadequately controlled hypertension; significant pulmonary disease including dyspnea at rest, patients requiring supplemental oxygen, or poor pulmonary reserve; or psychiatric illness/social situations that would limit compliance with study requirements * Patients with uncontrolled diabetes mellitus (fasting blood glucose controlled by medication, =\< 200 mg/dL allowed) * Patients who have had a hysterectomy or are planning to have an adjuvant hysterectomy following radiation as part of their cervical cancer treatment are ineligible * Patients scheduled to be treated with adjuvant consolidation chemotherapy at the conclusion of their standard chemoradiation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Experienced a DLT | Up to 5 weeks | Number of patients that experienced a DLT, evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. DLTs are defined as the following adverse events if considered at least possibly related to a component of the study therapy and which occur from the start of treatment until completion of EBRT, prior to initiation of brachytherapy (i.e. the first 5 weeks if no treatments are missed): Any nausea, vomiting, diarrhea and elevation of serum creatinine level Grade 3 toxicity not resolved with maximal intervention to Grade 0-2 over 7 days (except alopecia and fatigue); Any nausea, vomiting, diarrhea and elevation of serum creatinine level Grade 4 toxicity; Any other non-hematologic toxicity ≥Grade 3; Any hematologic toxicity of ≥ Grade 4; Grade ≥3 dyspnea; Inability to deliver at least 20 of the scheduled 25 administrations of triapine at the planned dose, allowing for 2 weeks to make up missed radiation days. Inability to deliver |
| Tmax | Up to 24 hours after dosing | Time to maximum concentration, |
| AUC | Up to 24 hours after dosing | Area Under the Concentration-Time Curve (AUC 0-last) |
| Elimination Half-life (t 1/2) | Up to 24 hours after dosing | — |
| Maximum Tolerated Dose (MTD) | Up to 5 weeks | The MTD was determined following a standard 3+3 design is as follows: Escalation at 0/3 DLTs, dose-reduction if \>1/3 DLT, and expansion to 6 if 1/3 DLTs. DLT is defined as the severe toxicity event that leads to the termination of the treatment as defined in section 5.5. The highest dose level where \<2/6 DLTs are observed will be declared MTD |
| Bioavailability of Triapine | Up to 2 weeks | The oral bioavailability of the oral form of the triapine will be measured as a numeric value using mass spectrophotometry. |
| Cmax | Up to 24 hours after dosing | Maximum concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Overall Response Rate | 3 months post-treatment | Clinical response at the recommended phase 2 dose per RECIST v1.1 Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. |
| Progression Free Survival (PFS) | Up to 4 years and 2 months from start of treatment | Median number of months that patients survive without disease progression from end of treatment. Per RECIST v1.1, Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). |
| Overall Survival (OS) | Up to 4 years and 2 months from start of treatment | Median number of months that patients remain alive after end of treatment. |
| Fludeoxyglucose F18-Positron Emission Tomography Computed Tomography Metabolic Complete Response (mCR) Rate | At 3 months post-treatment | The mCR rate at recommended phase 2 dose, defined as a metabolic complete response on PET/CT will be defined as greater than -66% reduction in tumor FDG uptake at sites of abnormal tumor FDG uptake noted on pre-treatment FDG-PET study (considering normal cardiac or liver blood pool). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Triapine (100mg) + Chemoradiation) Patients undergo pelvic EBRT or IMRT 5 days per week for 5 weeks (25 fractions) with a 3-day boost in week 6, and 1 or 2 applications of LDR brachytherapy in week 6 or 5 fractions of HDR brachytherapy at week 4 or 5. Patients also receive triapine IV over 120 minutes on day 1 and PO on days 2-5, 8-12, 15-19, 22-26, and 29-33 within 90 minutes after pelvic irradiation, and cisplatin IV over 60-120 minutes once weekly for 5 weeks (days 2, 9, 16, 23, and 30). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients may receive a 6th cycle of cisplatin IV during the parametrial boost or any make-up radiation treatment in a sixth week of external beam radiotherapy. Patients undergo the collection of blood samples on study and undergo MRI and FDG-PET/CT during follow-up.
Biospecimen Collection: Undergo collection of blood samples
Brachytherapy: Undergo LDR brachytherapy
Cisplatin: Given IV
Computed Tomography: Undergo FDG-PET/CT
External Beam Radiation Therapy: Undergo pelvic EBRT
Fludeoxyglucose F-18: Undergo FDG-PET/CT
High-Dose Rate Brachytherapy: Undergo HDR brachytherapy
Intensity-Modulated Radiation Therapy: Undergo IMRT
Magnetic Resonance Imaging: Undergo MRI
Pharmacological Study: Correlative studies
Positron Emission Tomography: Undergo FDG-PET/CT
Triapine: Given IV and PO | 17 |
| Triapine (150mg) + Chemoradiation) Patients undergo pelvic EBRT or IMRT 5 days per week for 5 weeks (25 fractions) with a 3-day boost in week 6, and 1 or 2 applications of LDR brachytherapy in week 6 or 5 fractions of HDR brachytherapy at week 4 or 5. Patients also receive triapine IV over 120 minutes on day 1 and PO on days 2-5, 8-12, 15-19, 22-26, and 29-33 within 90 minutes after pelvic irradiation, and cisplatin IV over 60-120 minutes once weekly for 5 weeks (days 2, 9, 16, 23, and 30). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients may receive a 6th cycle of cisplatin IV during the parametrial boost or any make-up radiation treatment in a sixth week of external beam radiotherapy. Patients undergo the collection of blood samples on study and undergo MRI and FDG-PET/CT during follow-up. | 4 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Expansion Cohort | Did not complete treatment regimen | 1 | 0 |
Baseline characteristics
| Characteristic | Triapine (100mg) + Chemoradiation) | Total | Triapine (150mg) + Chemoradiation) |
|---|---|---|---|
| Age, Continuous | 51.0 years | 51.0 years | 46.5 years |
| ECOG ECOG = 0 | 12 Participants | 15 Participants | 3 Participants |
| ECOG ECOG = 1 | 5 Participants | 6 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 19 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Histology adenocarcinoma | 3 Participants | 5 Participants | 2 Participants |
| Histology adenosquamous | 1 Participants | 1 Participants | 0 Participants |
| Histology squamous cell carcinoma | 13 Participants | 15 Participants | 2 Participants |
| Primary Site Cervix | 15 Participants | 19 Participants | 4 Participants |
| Primary Site Vagina | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 19 Participants | 4 Participants |
| Sex: Female, Male Female | 17 Participants | 21 Participants | 4 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Smoking History No | 12 Participants | 14 Participants | 2 Participants |
| Smoking History Unknown | 0 Participants | 1 Participants | 1 Participants |
| Smoking History Yes | 5 Participants | 6 Participants | 1 Participants |
| Stage Stage l | 1 Participants | 2 Participants | 1 Participants |
| Stage Stage ll | 5 Participants | 6 Participants | 1 Participants |
| Stage Stage lll | 9 Participants | 11 Participants | 2 Participants |
| Stage Stage lV | 2 Participants | 2 Participants | 0 Participants |
| Stage at Diagnosis Stage IB | 1 Participants | 2 Participants | 1 Participants |
| Stage at Diagnosis Stage II | 1 Participants | 2 Participants | 1 Participants |
| Stage at Diagnosis Stage IIA | 1 Participants | 1 Participants | 0 Participants |
| Stage at Diagnosis Stage IIB | 3 Participants | 3 Participants | 0 Participants |
| Stage at Diagnosis Stage III | 1 Participants | 2 Participants | 1 Participants |
| Stage at Diagnosis Stage IIIB | 1 Participants | 1 Participants | 0 Participants |
| Stage at Diagnosis Stage IIIC | 7 Participants | 8 Participants | 1 Participants |
| Stage at Diagnosis Stage IVA | 2 Participants | 2 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 4 |
| other Total, other adverse events | 17 / 17 | 4 / 4 |
| serious Total, serious adverse events | 8 / 17 | 2 / 4 |
Outcome results
Primary
AUC
Area Under the Concentration-Time Curve (AUC 0-last)
Time frame: Up to 24 hours after dosing
Population: Treated patients for whom samples were able to be collected
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| All Participants | AUC | 990 ug/L x h | Standard Deviation 2.09 |
| Triapine (150mg) + Chemoradiation) | AUC | 990 ug/L x h | Standard Deviation 1.42 |
Primary
Bioavailability of Triapine
The oral bioavailability of the oral form of the triapine will be measured as a numeric value using mass spectrophotometry.
Time frame: Up to 2 weeks
Population: Patients that had both PO and IV triapine PK samples
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| All Participants | Bioavailability of Triapine | 60 percentage |
| Triapine (150mg) + Chemoradiation) | Bioavailability of Triapine | 54 percentage |
Primary
Cmax
Maximum concentration
Time frame: Up to 24 hours after dosing
Population: Treated patients for whom PK samples were able to be collected
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Cmax | 476 ug/L | Standard Deviation 1.9 |
| Triapine (150mg) + Chemoradiation) | Cmax | 344 ug/L | Standard Deviation 1.91 |
Primary
Elimination Half-life (t 1/2)
Time frame: Up to 24 hours after dosing
Population: Treated patients for whom PK samples were able to be collected
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Elimination Half-life (t 1/2) | 1.5 hours | Standard Deviation 1.3 |
| Triapine (150mg) + Chemoradiation) | Elimination Half-life (t 1/2) | 1.5 hours | Standard Deviation 1.3 |
Primary
Maximum Tolerated Dose (MTD)
The MTD was determined following a standard 3+3 design is as follows: Escalation at 0/3 DLTs, dose-reduction if \>1/3 DLT, and expansion to 6 if 1/3 DLTs. DLT is defined as the severe toxicity event that leads to the termination of the treatment as defined in section 5.5. The highest dose level where \<2/6 DLTs are observed will be declared MTD
Time frame: Up to 5 weeks
Population: All treated patients evaluable for DLTs
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Maximum Tolerated Dose (MTD) | 100 mg |
Primary
Number of Patients Who Experienced a DLT
Number of patients that experienced a DLT, evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. DLTs are defined as the following adverse events if considered at least possibly related to a component of the study therapy and which occur from the start of treatment until completion of EBRT, prior to initiation of brachytherapy (i.e. the first 5 weeks if no treatments are missed): Any nausea, vomiting, diarrhea and elevation of serum creatinine level Grade 3 toxicity not resolved with maximal intervention to Grade 0-2 over 7 days (except alopecia and fatigue); Any nausea, vomiting, diarrhea and elevation of serum creatinine level Grade 4 toxicity; Any other non-hematologic toxicity ≥Grade 3; Any hematologic toxicity of ≥ Grade 4; Grade ≥3 dyspnea; Inability to deliver at least 20 of the scheduled 25 administrations of triapine at the planned dose, allowing for 2 weeks to make up missed radiation days. Inability to deliver
Time frame: Up to 5 weeks
Population: All treated patients evaluable for DLTs
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants | Number of Patients Who Experienced a DLT | 1 Participants |
| Triapine (150mg) + Chemoradiation) | Number of Patients Who Experienced a DLT | 2 Participants |
Primary
Tmax
Time to maximum concentration,
Time frame: Up to 24 hours after dosing
Population: Treated patients for whom samples were able to be collected
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Tmax | 0.9 hours | Standard Deviation 3 |
| Triapine (150mg) + Chemoradiation) | Tmax | 1.5 hours | Standard Deviation 1.5 |
Secondary
Clinical Overall Response Rate
Clinical response at the recommended phase 2 dose per RECIST v1.1 Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time frame: 3 months post-treatment
Population: Patients who received at least 3 weeks of therapy (cisplatin + triapine) and have had their disease re-evaluated (with a 3 month post treatment PET-CT) will be considered evaluable for response. (Note: Patients who exhibit objective disease progression prior to the end of cycle 1 will also be considered evaluable.)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | Clinical Overall Response Rate | Complete Response | 62 percentage response evaluable patient |
| All Participants | Clinical Overall Response Rate | Stable Disease | 15 percentage response evaluable patient |
| All Participants | Clinical Overall Response Rate | Partial Response | 15 percentage response evaluable patient |
| All Participants | Clinical Overall Response Rate | Progressive Disease | 8 percentage response evaluable patient |
| Triapine (150mg) + Chemoradiation) | Clinical Overall Response Rate | Partial Response | 0 percentage response evaluable patient |
| Triapine (150mg) + Chemoradiation) | Clinical Overall Response Rate | Complete Response | 100 percentage response evaluable patient |
| Triapine (150mg) + Chemoradiation) | Clinical Overall Response Rate | Progressive Disease | 0 percentage response evaluable patient |
| Triapine (150mg) + Chemoradiation) | Clinical Overall Response Rate | Stable Disease | 0 percentage response evaluable patient |
Secondary
Fludeoxyglucose F18-Positron Emission Tomography Computed Tomography Metabolic Complete Response (mCR) Rate
The mCR rate at recommended phase 2 dose, defined as a metabolic complete response on PET/CT will be defined as greater than -66% reduction in tumor FDG uptake at sites of abnormal tumor FDG uptake noted on pre-treatment FDG-PET study (considering normal cardiac or liver blood pool).
Time frame: At 3 months post-treatment
Population: Patients who received at least 3 weeks of therapy (cisplatin + triapine), and had their disease re-evaluated with a 3-month post treatment 18F-FDG-PET/CT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Fludeoxyglucose F18-Positron Emission Tomography Computed Tomography Metabolic Complete Response (mCR) Rate | 62 percentage response-evaluable patients |
| Triapine (150mg) + Chemoradiation) | Fludeoxyglucose F18-Positron Emission Tomography Computed Tomography Metabolic Complete Response (mCR) Rate | 100 percentage response-evaluable patients |
Secondary
Overall Survival (OS)
Median number of months that patients remain alive after end of treatment.
Time frame: Up to 4 years and 2 months from start of treatment
Population: Zero treated patients experienced the event of death.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Participants | Overall Survival (OS) | NA months |
| Triapine (150mg) + Chemoradiation) | Overall Survival (OS) | NA months |
Secondary
Progression Free Survival (PFS)
Median number of months that patients survive without disease progression from end of treatment. Per RECIST v1.1, Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time frame: Up to 4 years and 2 months from start of treatment
Population: Treated patients evaluable for clinical response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Participants | Progression Free Survival (PFS) | NA months |
| Triapine (150mg) + Chemoradiation) | Progression Free Survival (PFS) | NA months |