Integrated Dose Escalation for Advanced, Localized Gynecologic Cancer (The IDEAL - GYN Trial)

Study Overview
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Brief Summary
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The purpose of this study is to determine the maximum tolerated dose of integrated boost radiation therapy when given with concurrent chemotherapy (cisplatin).

Official Title
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Integrated Dose Escalation for Advanced, Localized Gynecologic Cancer (The IDEAL - GYN Trial)

Conditions
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Cancer of the Cervix, Cervical Neoplasms

Intervention / Treatment
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* Radiation: Boost radiation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Boost Radiation: Dose Level 1<br>2.4 Gy X 25 fractions = 60 Gy | Radiation: Boost radiation<br>* 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<br>|
| Experimental: Boost Radiation: Dose level 2<br>2.6 Gy X 25 fractions = 65 Gy | Radiation: Boost radiation<br>* 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<br>|
| Experimental: Boost Radiation: Dose level 3<br>2.8 Gy x 25 fractions = 70 Gy | Radiation: Boost radiation<br>* 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<br>|
| Experimental: Experimental: Boost Radiation Dose Level 0<br>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 | Radiation: Boost radiation<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | During RT to 6 weeks post RT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Local-regional Control With Integrated Boost Radiation Therapy (TTLR) | Local-regional control is defined as local control without any nodal recurrence. | 3 years following treatment | 
| Time to Distant Recurrence (TTDR) |  | 3 years after treatment | 
| Disease Free Survival (DFS) |  | 3 years after treatment | 
| Overall Survival (OS) |  | 3 years after treatment | 
| 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. | 6 weeks following treatment | 
| 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. | 3 years following treatment |