Clinical trial NCT03949283: Cancer Stem Cell Assay Directed Chemotherapy in Recurrent Platinum Resistant Ovarian Cancer
Official title: Standard Chemotherapy Versus Cancer Stem Cell Assay Directed Chemotherapy in Recurrent Platinum Resistant Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Recurrent Ovarian Carcinoma
Platinum-resistant Ovarian Cancer
Keywords: Ovarian cancer
Platinum resistant
ChemoID
Cytotoxicity assay
Cancer Stem Cells
Lead sponsor: Cordgenics, LLC
Sponsor class: INDUSTRY
First posted: 2019-05-14
Enrollment: 150
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: TREATMENT

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

Population studied will be female participants experiencing a recurrent platinum-resistant ovarian cancer (no mucinous, low grade serous, or pure sarcoma types), with ≤ 5 prior treatments, and a performance status 0-1.

Detailed description: This study is designed as a parallel group randomized controlled clinical trial to determine if recurrent platinum resistant epithelial ovarian cancer (EOC) patients treated with chemotherapy predicted by the ChemoID assay will have better outcomes than patients treated with standard-of-care control therapy chosen by the physician.

Upon obtaining informed consent, all eligible participants affected by recurrent platinum-resistant ovarian cancer (no mucinous, low grade serous, or pure sarcoma types), with ≤ 5 prior treatments, and a performance status 0-1 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 (chemotherapy chosen by the Physician from a provided list), or to a study arm of 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 number of prior platinum treatments and BRCA status to ensure balance within these cells.

Eligibility criteria: Inclusion Criteria:

1. Informed consent obtained and signed.
2. Participant is willing and able to commit to study procedures including long-term follow-up visit(s);
3. Participant must be a female and at least 18 years of age at the time of enrollment.
4. Negative pregnancy test for women of childbearing potential.
5. Participant has been diagnosed with recurrent platinum resistant epithelial ovarian, peritoneal, or fallopian tube carcinoma.
6. Participants must have an evaluable disease - defined as one of the following:

1) RECIST 1.1 measurable disease (defined as one or more solid and/or cystic tumors on cross-sectional imaging that measures 1 cm or greater in long axis and/or lymph nodes measuring 1.5 cm or greater in short axis) 2) Evaluable disease (defined as solid and/or cystic tumors on radiographic imaging or physical exam that do not meet RECIST 1.1 definitions for target lesions) with elevated CA125 (GCIG recurrence and response criteria) by more than 2 times the upper limits of normal, confirmed in two successive samples, drawn at least one week apart).

7. Participant has agreed to provide a core biopsy of the primary site, a secondary metastatic site, or to undergo a paracentesis or thoracentesis for fluid collection.

8. An adequate fresh sample can be provided and submitted for ChemoID testing.

9. Participant has disease of one of the following histologic epithelial cell types: high-grade serous adenocarcinoma, endometrioid adenocarcinoma, undifferentiated carcinoma, transitional cell carcinoma, clear cell carcinoma, or adenocarcinoma, not otherwise specified (N.O.S.). Cytologic confirmation of diagnosis is acceptable for participants treated with neoadjuvant therapy who have not had a surgical procedure for a histologic confirmation. Patients with low-grade serous or mucinous adenocarcinoma are not eligible, nor are patients with pure ovarian sarcomas.

10. Participant has received ≤ 5 prior regimens including at least one platinum-based regimen for their ovarian, peritoneal, or fallopian tube carcinoma.

11. Participant must have an estimated life expectancy of greater than six months, as determined by the investigator.

12. Participant requires chemotherapy and the investigator plans to administer one of the regimens of interest as deemed by her physician.

13. Participant must have an ECOG Performance Status Score of ≤ 2, KPS≥70, or 0-2 GOG status.

14. Adequate laboratory values within 60 days of enrollment to study defined as follows:

1. ANC ≥ 1500/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.

Exclusion Criteria:

1. Use of Avastin planned to treat participant.
2. Participant has ovarian stromal, germ cell tumors or pure sarcomas.
3. Participant has borderline carcinoma (uncertain malignant potential), mutinous or low-grade serous carcinoma.
4. Participant is pregnant or lactating.
5. Participants of childbearing potential not employing adequate contraception.
6. Participants who are at risk of failure of compliance to the visit schedules and procedures including those with psychiatric disease that would substantially impact compliance or consent.
7. Estimated life expectancy of \<6 months, as estimated by the investigator in consultation with participating oncologists.
8. Participants with symptomatic cardiac conditions (i.e. NYHA class III/IV or uncompensated angina).
9. Enrollment in another clinical study that precludes allowing the oncologist to select chemotherapy regimens.
10. Previously participated in this study.
11. 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).
12. CA-125 only disease without RECIST 1.1 measurable or otherwise evaluable disease.
13. Patients with third space fluid (for example pleural effusions) as only site of disease.
14. Participant 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: Objective response rate
timeFrame: 24 months
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 24 months
measure: Duration of Response
timeFrame: 24 months
measure: CA125 levels
timeFrame: 24 months
measure: Health-Related Quality of Life (HRQOL)
timeFrame: 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Kaiser Permanente
state: California
city: Miami
country: United States
facility: Miami Cancer Institute/Baptist Health South Florida
state: Florida
city: New Orleans
country: United States
facility: LSU Health Sciences Center
state: Louisiana
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Institute
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Pittsburgh
country: United States
facility: West Penn Hospital, Allegheny Health Network
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston Area Medical Center (CAMC)
state: West Virginia
city: Huntington
country: United States
facility: Edwards Comprehensive Cancer Center - Cabell Huntington Hospital
state: West Virginia
Study officials:
affiliation: University of Cincinnati
name: Thomas Herzog, MD
role: STUDY_CHAIR
References:
citation: Howard CM, Zgheib NB, Bush S 2nd, DeEulis T, Cortese A, Mollo A, Lirette ST, Denning K, Valluri J, Claudio PP. Clinical relevance of cancer stem cell chemotherapeutic assay for recurrent ovarian cancer. Transl Oncol. 2020 Dec;13(12):100860. doi: 10.1016/j.tranon.2020.100860. Epub 2020 Aug 28.
citation: Howard CM, Bush S 2nd, Zgheib NB, Lirette ST, Cortese A, Mollo A, Valluri J, Claudio PP. Cancer Stem Cell Assay for the Treatment of Platinum-Resistant Recurrent Ovarian Cancer. HSOA J Stem Cells Res Dev Ther. 2021;7(3):076. doi: 10.24966/srdt-2060/100076. Epub 2021 Sep 9.