Clinical trial NCT03632798: Avastin Plus Chemotherapy vs. Avastin Plus Chemotherapy Guided by Cancer Stem Cell Test in Recurrent Ovarian Cancer
Official title: Avastin Plus Chemotherapy vs. Avastin Plus Chemotherapy Chosen by Cancer Stem Cell Chemosensitivity Testing in the Management of Patients With Recurrent Platinum-Resistant or -Sensitive Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Recurrent Ovarian Cancer
Keywords: ChemoID
cancer stem cells
drug response assay
ovarian cancer
Lead sponsor: Cordgenics, LLC
Sponsor class: INDUSTRY
First posted: 2018-08-15
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: parallel group randomized controlled clinical trial
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this randomized clinical study is to confirm the utility of chemosensitivity (ChemoID) tumor testing on cancer stem cells as a predictor of clinical response in recurrent epithelial ovarian cancer (EOC), fallopian tube, or primary peritoneal cancer, regardless of platinum sensitivity.

Population studied will be female participants experiencing a 1st, 2nd, or 3rd recurrence of any stage epithelial ovarian cancer.

Detailed description: This study is designed as a parallel group randomized controlled clinical trial to determine if recurrent Epithelial Ovarian Cancer (EOC) patients treated with Bevacizumab plus drugs predicted by the ChemoID assay will have better outcomes than patients treated with standard-of-care control therapy (Bevacizumab plus chemotherapy chosen by the Physician).

Upon obtaining informed consent, all eligible participants affected by 1st, 2nd, or 3rd relapse of EOC regardless of platinum sensitivity (both platinum sensitive and resistant) will have a tumor biopsy or a cancer-positive fluid collection sample to undergo ChemoID drug response testing with multiple FDA-approved chemotherapeutic agents.

Eligible participants will be randomized to a standard treatment arm with control treatment (Bevacizumab plus chemotherapy chosen by the Physician from the provided list), or to a study arm of Bevacizumab plus FDA-approved drugs selected by the ChemoID drug response assay.

A stratified randomization approach for treatment arm assignment will be used with strata based on relapse number, platinum sensitivity, and study site to ensure balance within these cells.

Eligibility criteria: Inclusion Criteria:

* 1. Informed consent obtained and signed;
* 2. Willing and able to commit to study procedures including long-term follow-up visit(s);
* 3. At least 18 years old at the time of enrollment;
* 4. Negative pregnancy test for women of childbearing potential
* 5. Experiencing 1st, 2nd, or 3rd recurrent epithelial ovarian cancer of any stage regardless of platinum sensitivity, (platinum-sensitive, -resistant, or -refractory);
* 6. Histopathological or cytological confirmation of recurrent epithelial ovarian carcinoma, peritoneal cancer or fallopian tube cancer.
* 7. Evaluable disease - defined as RECIST 1.1 measurable disease OR not measurable disease (defined as solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions OR ascites and/or pleural effusion that has been pathologically demonstrated to be disease-related in the setting of a CA125 \> 2x ULN).
* 8. At least 30 days post-cytotoxic chemotherapy and/or monoclonal antibody therapy prior to enrollment;
* 9. Toxicities of prior therapy (excepting alopecia) should be resolved to less than or equal to Grade 1 as per CTCAE v4.0 (http://ctep.cancer.gov/protocol development/electronic_applications/ctc.htm). Patients with long-standing stable grade 2 neuropathy may be considered after discussion with the Study Chair.
* 10. ECOG Performance Status Score of ≤ 2, KPS≥70, or 0-1 GOG status
* 11. Adequate laboratory values within 60 days of enrollment to study defined as follows:

  1. WBC ≥ 3000/mm3
  2. Hgb ≥ 10 mg/dl
  3. Hct ≥ 28%
  4. Platelet count ≥ 100,000/μL
  5. Serum creatinine ≤ 2.0 mg/dl
  6. Total bilirubin ≤ 2.5 mg/dl
  7. AST/SGOT ≤ 3 times ULN. If intrahepatic liver metastases are present, AST and ALT must be ≤ 5 times institutional ULN.
  8. Random urine protein/creatinine ratio ≤ 1 or 24 hour urine protein \< 0.1 gram.
* 12. Appropriate for tissue sampling either by tumor biopsy or peritoneal or pleural fluid collection.

Exclusion Criteria:

* 1. Estimated life expectancy of \<6 months, as estimated by the investigator in consultation with participating oncologists;
* 2. Ovarian cancer of a low grade serous, mucinous, or clear cell histology;
* 3. Uncontrolled diabetes;
* 4. Patients with clinically significant proteinuria; urine protein should be screened by urine protein-creatinine ratio (UPCR); the UPCR has been found to correlate directly with the amount of protein excreted in a 24 hour urine collection; specifically, a UPCR of 1.0 is equivalent to 1.0 gram of protein in a 24-hour urine collection; obtain at least 4 ml of a random urine sample in a sterile container (does not have to be a 24-hour urine); send sample to lab with request for urine protein and creatinine levels (separate requests); the lab will measure protein concentration (mg/dL) and creatinine concentration (mg/dL); the UPCR is derived as follows: protein concentration (mg/dL)/creatinine (mg/dL); patients must have a UPCR ≤ 1.0 to allow participation in the study;
* 5. Symptomatic cardiac conditions;
* 6. Contraindications to bevacizumab including uncontrolled hypertension, known arterial or venous thromboembolism, known nephrotic syndrome, history of abdominal fistula, GIP, or intra-abdominal abscess; clinical signs or symptoms of GI obstruction and/or requirement for parenteral hydration or nutrition; nonhealing wound, ulcer, or bone fracture; bleeding diathesis or significant coagulopathy; known CNS disease, clinically significant cardiovascular disease; and a major surgical procedure within 28 days of enrollment or anticipated to occur while participating in study;
* 7. Enrollment in another clinical study that precludes allowing the oncologist to select chemotherapy regimens;
* 8. Previously participated in this study;
* 9. Any condition that would, in the opinion of the investigator, place the participant at an unacceptable risk, or render the participant unable to meet the requirements of the protocol (including long-term study follow-up).
* 10. Documented history of ovarian cancer of a low malignant potential phenotype or unclear cell histology.
* 11. CA-125 only disease without RECIST 1.1 measurable or otherwise evaluable disease
* 12. Patients may not use any complementary or alternative medicines including natural herbal products or folk remedies as they may interfere with the effectiveness of the study treatments.

Primary outcomes:
measure: Progression free survival (PFS)
timeFrame: 36 months
Secondary outcomes:
measure: Median Overall Survival (OS)
timeFrame: 36 months
measure: Objective Tumor Response
timeFrame: 36 months
measure: HRQOL
timeFrame: 36 months
Other outcomes:
Locations:
city: Jackson
country: United States
facility: Univeristy of Mississippi Medical Center
state: Mississippi
city: Charleston
country: United States
facility: Charleston Area Medical Center
state: West Virginia
city: Huntington
country: United States
facility: Edwards Comprehensive Cancer Center - Cabell Huntington Hospital
state: West Virginia
Study officials:
affiliation: University of Mississippi Medical Center
name: Kelly J Wilkinson, MD
role: PRINCIPAL_INVESTIGATOR
References: