LDFWART With Docetaxel in Patients With Platinum-Resistant Recurrent Ovarian Carcinoma

Study Overview
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Brief Summary
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The ultimate clinical aim of this proposed phase I trial is to evaluate the toxicity and determine the recommended phase II dose of combining the effect of LDFWART following administration of docetaxel for 6 cycles in patients with recurrent platinum-resistant ovarian cancer.

Official Title
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A Phase I Study Using Low-Dose Fractionated Whole Abdominal Radiation Therapy (LDFWART) As A Docetaxel Chemo-Potentiator for Patients With Platinum-Resistant Recurrent Ovarian Carcinoma

Conditions
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Ovarian Cancer, Ovarian Carcinoma, Recurrent Ovarian Cancer, Recurrent Ovarian Carcinoma

Intervention / Treatment
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* Radiation: Low Dose Fractionated Whole Abdominal Radiation Therapy
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Patients must have platinum-resistant disease relapsing within 6 months or less from the date of their last cycle of initial adjuvant chemotherapy recurrent adenocarcinoma from a primary ovarian, tubal, or peritoneal cancer following first-line chemotherapy for metastatic disease. There is no limit on prior number of chemotherapy regimens. Patients who have received prior systemic docetaxel and platinum-based chemotherapy are eligible 1.1 Patients must have ≥ 1cm measurable disease on imaging studies independent of patients having an optional surgical salvage procedure. 2. Patients must have a life expectancy of at least 6 months. 3. Patients must have Karnofsky performance status of ≥ 60 or Gynecology Oncology (GOG) performance status of ≤ 2 (see www.GOG.org website). 4. Age 18 - 80 years old 5. Patients must have an adequate bone marrow, renal, and hepatic function: 5.1 WBC: ≥ 3,000 /mcl 5.2 ANC: ≥ 1,500 /mcl 5.3 Platelets: ≥ 100,000 /mcl 5.4 Creatinine: < 2.0 mg/dcl 5.5 Bilirubin: < 1.5x institutional normal value 5.6 LDH, GGT, SGPT (ALT), SGOT (AST), and ALK Phos:< 3x institutional normal value. 6. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: 1. Patients who have received prior radiotherapy to the chest, whole abdomen, or lower extremities above the knees. 2. Patients who have received prior radiation therapy to the head, neck, or lower extremities below the knees if greater than 3 years prior to study entry. 3. Evidence of extra-abdominal extension of disease (such as groin nodes, lung, supraclavicular nodes, and pleural fluid). 4. Patients may not be receiving any other investigational agents within 4 weeks preceding the start of study treatment) or chemotherapy for at least 3 weeks preceding the start of study treatment. 5. Patients who have been diagnosed with another prior malignant tumor within 3 years of study entry, excluding non-melanoma skin cancer and carcinoma in situ of the cervix. 6. Patients with prior history of a severe hypersensitivity reaction to paclitaxel (polysorbate 80-Cremophor). 7. Patients with current history of uncontrolled hypertension, angina pectoris, heart failure, cardiac dysrhythmias, pericardial disease, cardiomyopathy, or active infection. 8. Presence of any medical condition that in the opinion of the investigator deems the patient unable to participate. 9. Females of child-bearing potential. It is expected that ovarian cancer patients would have had a hysterectomy and/or oophorectomy as part of the original standard of care. 10. Patients that are < 18 yrs. of age or > 80 yrs. of age.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LDFWART + Docetaxel<br>This study has 6 treatment cycles given at 3 weeks intervals ± 3 days. A cycle is defined as 1 treatment of morning Docetaxel and afternoon Low Dose Fractionated Whole Abdominal Radiation Therapy (LDFWART). The first day of the first treatment is designated study day 1. | Radiation: Low Dose Fractionated Whole Abdominal Radiation Therapy<br>* A single fraction of LDFWART will be given 6-8 hours after the start of morning administration of Docetaxel for 6 cycles (the time of the start Docetaxel will be counted as the frame of reference for when the LDFWART can be given).<br>* Other names: LDFWART;Drug: Docetaxel<br>* Chemotherapy will consist of 6 cycles of Docetaxel. Each cycle will follow standard of care and will be scheduled every 3 weeks ± 3 days. Chemotherapy should be administered in the morning to allow 6-8 hours before Radiation Therapy. On Day 1 of each cycle, chemotherapy will consist of Docetaxel 60 mg/m² infused intravenously over 30-60 minutes (with premedication of dexamethasone 10 mg given IV 30-60 minutes prior to docetaxel administration).<br>* Other names: Taxotere;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Experiencing Adverse Events as a Measure of Safety and Tolerability | Number of subjects experiencing adverse events after receiving protocol therapy. | 3 years | 
| Recommended Phase II Dose of LDFWART | The recommended phase II dose of low-dose whole abdominal radiation therapy (LDFWART) when used in conjunction with 6 cycles of docetaxel chemotherapy. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Experiencing Complete or Partial Response to Protocol Therapy | Number of subjects experiencing complete response (CR) or partial response (PR) according to RECIST Criteria Version 1.1 | Up to 5 years | 
| The rate of Overall Survival in subjects receiving protocol therapy | Observed length of life from start of treatment to cause of death | Up to 5 years | 
| The rate of Progression-Free Survival in subjects receiving protocol therapy. | Length of time from start of treatment to the time of documented disease progression in study subjects | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low Dose Fractionated Whole Abdominal Radiation Therapy, LDFWART, Docetaxel, Ovarian Cancer, Ovarian Carcinoma, Platinum-Resistant