Cancer of the Cervix, Cervical Neoplasms
Conditions
Brief summary
The purpose of this study is to determine the maximum tolerated dose of integrated boost radiation therapy when given with concurrent chemotherapy (cisplatin).
Interventions
RADIATIONBoost radiation
Many studies have utilized a sequential boost to deliver a total dose of 55 - 60 Gy to the pelvic sidewall (covering the lower pelvic lymph nodes), including 8-10 Gy that is usually delivered with brachytherapy (1-3). This study treatment plan will escalate the dose to pelvic and para-aortic nodal disease from 60 Gy in 2.4 Gy per fraction to 70Gy in 2.8 Gy per fraction in 3 dose cohorts, using an integrated boost technique utilizing the same number of fractions for all cohorts (25 fractions) while the elective volumes are held constant at 45Gy
Sponsors
Duke University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Biopsy confirmed malignancy of the gynecologic tract * Involved pelvic or para-aortic lymph nodes * Treatment plan to include delivery of concurrent chemoradiotherapy. * Good performance status * Negative pregnancy test in women of child-bearing potential * Signed study-specific informed consent * Lab results within study specific limits
Exclusion criteria
* Prior radiation to the abdomen or pelvis * A history of Scleroderma or Inflammatory bowel disease * Contraindication to chemotherapy or radiation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose of Integrated Boost Radiation Therapy, Administered With IMRT Technique With Concurrent Chemotherapy (Cisplatin). | During RT to 6 weeks post RT | Concurrent radiation therapy and chemotherapy is the standard of care for node positive cervical cancer. While there are several acceptable means to boost the disease in the low pelvis (i.e. brachytherapy, IMRT, or external beam), there is limited research into boosting gross disease in the pelvis or para-aortic region. This protocol is designed to determine the maximum tolerated dose of treating tumor bearing regions within the abdomen and pelvis, using an integrated boost technique and concurrent chemotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Distant Recurrence (TTDR) | 3 years after treatment | — |
| Disease Free Survival (DFS) | 3 years after treatment | — |
| Time to Local-regional Control With Integrated Boost Radiation Therapy (TTLR) | 3 years following treatment | Local-regional control is defined as local control without any nodal recurrence. |
| Number of Participants With Acute Dose Limiting Toxicities (DLT) | 6 weeks following treatment | Acute DLT will be defined based on the side effects inherent from radiation therapy for gynecologic cancers, including effects on bowel, bladder, and skin.Since integrated radiation dose escalation is unlikely to substantially affect the hematopoietic system, only non-hematologic, grade 3-4, acute toxicity will be considered the primary dose-limiting toxicity (acute DLT). Dose limiting toxicity will include any of the following during treatment or within 6 weeks of completion: Acute Grade 3-4 enteritis or proctitis, Acute Grade 3-4 bladder toxicity, Acute Grade 4 dermatologic toxicity. |
| Number of Participants With Late Dose Limiting Toxicities (DLT) | 3 years following treatment | Late DLTs will be defined at grade 3-4 GI or GU toxicity with onset after 6 weeks of treatment. |
| Overall Survival (OS) | 3 years after treatment | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Boost Radiation: Dose Level 1 2.4 Gy X 25 fractions = 60 Gy | 3 |
| Boost Radiation: Dose Level 2 2.6 Gy X 25 fractions = 65 Gy | 3 |
| Boost Radiation: Dose Level 3 2.8 Gy x 25 fractions = 70 Gy | 6 |
| Boost Radiation Dose Level 0 If the 2 dose limiting toxicities are documented at dose level 1, therapy will be de-escalated to Dose level 0 defined below.
Dose level 0: 2.2 Gy X 25 fractions = 55 Gy | 0 |
| Total | 12 |
Baseline characteristics
| Characteristic | Boost Radiation: Dose Level 1 | Boost Radiation: Dose Level 2 | Boost Radiation: Dose Level 3 | Boost Radiation Dose Level 0 | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 2 Participants | 6 Participants | 0 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 6 Participants | 0 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 3 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 6 Participants | 0 Participants | 9 Participants |
| Region of Enrollment United States | 3 Participants | 3 Participants | 6 Participants | — | 12 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants | 0 Participants | 12 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 1 / 3 | 1 / 6 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 6 / 6 |
| serious Total, serious adverse events | 2 / 3 | 0 / 3 | 1 / 6 |
Outcome results
Primary
Maximum Tolerated Dose of Integrated Boost Radiation Therapy, Administered With IMRT Technique With Concurrent Chemotherapy (Cisplatin).
Concurrent radiation therapy and chemotherapy is the standard of care for node positive cervical cancer. While there are several acceptable means to boost the disease in the low pelvis (i.e. brachytherapy, IMRT, or external beam), there is limited research into boosting gross disease in the pelvis or para-aortic region. This protocol is designed to determine the maximum tolerated dose of treating tumor bearing regions within the abdomen and pelvis, using an integrated boost technique and concurrent chemotherapy.
Time frame: During RT to 6 weeks post RT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Arm | Maximum Tolerated Dose of Integrated Boost Radiation Therapy, Administered With IMRT Technique With Concurrent Chemotherapy (Cisplatin). | 70 Gray (Gy) |
Secondary
Disease Free Survival (DFS)
Time frame: 3 years after treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm | Disease Free Survival (DFS) | 1.3 years | Standard Deviation 0.1 |
| Boost Radiation: Dose Level 1 (60 Gy) | Disease Free Survival (DFS) | 0.85 years | — |
| Boost Radiation: Dose Level 2 (65) | Disease Free Survival (DFS) | 1.05 years | Standard Deviation 0.23 |
| Boost Radiation: Dose Level 3 (70Gy) | Disease Free Survival (DFS) | 1.34 years | Standard Deviation 0.2 |
Secondary
Number of Participants With Acute Dose Limiting Toxicities (DLT)
Acute DLT will be defined based on the side effects inherent from radiation therapy for gynecologic cancers, including effects on bowel, bladder, and skin.Since integrated radiation dose escalation is unlikely to substantially affect the hematopoietic system, only non-hematologic, grade 3-4, acute toxicity will be considered the primary dose-limiting toxicity (acute DLT). Dose limiting toxicity will include any of the following during treatment or within 6 weeks of completion: Acute Grade 3-4 enteritis or proctitis, Acute Grade 3-4 bladder toxicity, Acute Grade 4 dermatologic toxicity.
Time frame: 6 weeks following treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Arm | Number of Participants With Acute Dose Limiting Toxicities (DLT) | 1 Participants |
| Boost Radiation: Dose Level 1 (60 Gy) | Number of Participants With Acute Dose Limiting Toxicities (DLT) | 0 Participants |
| Boost Radiation: Dose Level 2 (65) | Number of Participants With Acute Dose Limiting Toxicities (DLT) | 0 Participants |
| Boost Radiation: Dose Level 3 (70Gy) | Number of Participants With Acute Dose Limiting Toxicities (DLT) | 1 Participants |
Secondary
Number of Participants With Late Dose Limiting Toxicities (DLT)
Late DLTs will be defined at grade 3-4 GI or GU toxicity with onset after 6 weeks of treatment.
Time frame: 3 years following treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Arm | Number of Participants With Late Dose Limiting Toxicities (DLT) | 1 Participants |
| Boost Radiation: Dose Level 1 (60 Gy) | Number of Participants With Late Dose Limiting Toxicities (DLT) | 0 Participants |
| Boost Radiation: Dose Level 2 (65) | Number of Participants With Late Dose Limiting Toxicities (DLT) | 0 Participants |
| Boost Radiation: Dose Level 3 (70Gy) | Number of Participants With Late Dose Limiting Toxicities (DLT) | 1 Participants |
Secondary
Overall Survival (OS)
Time frame: 3 years after treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm | Overall Survival (OS) | 1.6 years | Standard Deviation 0.1 |
| Boost Radiation: Dose Level 1 (60 Gy) | Overall Survival (OS) | 0.85 years | — |
| Boost Radiation: Dose Level 2 (65) | Overall Survival (OS) | 1.08 years | — |
| Boost Radiation: Dose Level 3 (70Gy) | Overall Survival (OS) | 1.7 years | — |
Secondary
Time to Distant Recurrence (TTDR)
Time frame: 3 years after treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm | Time to Distant Recurrence (TTDR) | 1.4 years | Standard Deviation 0.1 |
| Boost Radiation: Dose Level 1 (60 Gy) | Time to Distant Recurrence (TTDR) | NA years | — |
| Boost Radiation: Dose Level 2 (65) | Time to Distant Recurrence (TTDR) | 1.2 years | — |
| Boost Radiation: Dose Level 3 (70Gy) | Time to Distant Recurrence (TTDR) | 1.29 years | Standard Deviation 0.22 |
Secondary
Time to Local-regional Control With Integrated Boost Radiation Therapy (TTLR)
Local-regional control is defined as local control without any nodal recurrence.
Time frame: 3 years following treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm | Time to Local-regional Control With Integrated Boost Radiation Therapy (TTLR) | 1.5 years | Standard Deviation 0.1 |
| Boost Radiation: Dose Level 1 (60 Gy) | Time to Local-regional Control With Integrated Boost Radiation Therapy (TTLR) | NA years | — |
| Boost Radiation: Dose Level 2 (65) | Time to Local-regional Control With Integrated Boost Radiation Therapy (TTLR) | 0.65 years | — |
| Boost Radiation: Dose Level 3 (70Gy) | Time to Local-regional Control With Integrated Boost Radiation Therapy (TTLR) | 1.52 years | Standard Deviation 0.04 |