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Folate Receptor in Diagnosing Ovarian Cancer Using Serum Samples From Patients With Newly Diagnosed Pelvic Mass or Previously Diagnosed Ovarian Cancer

Primary Purpose

Adnexal Mass, Borderline Ovarian Epithelial Tumor, Ovarian Clear Cell Tumor

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Dexamethasone

Laboratory Biomarker Analysis

Valproic Acid

About this trial

This is an interventional treatment trial for Adnexal Mass

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

For study Arm 1, female subjects of childbearing potential or less than 2 years postmenopausal agree to use an acceptable form of contraception from the time of signing informed consent until 30 days after study completion unless total hysterectomy performed at the time of original operation
Able to provide informed consent
Performance status Eastern Cooperative Oncology Group (ECOG) 0-2
Study Arm 1: primary diagnosis of a pelvic or adnexal mass of presumed gynecologic origin who is scheduled for operative resection
Study Arm 2: previously diagnosed with a non-mucinous epithelial ovarian carcinoma (including serous, clear cell, and endometrioid histologies as well as borderline ovarian tumors) currently undergoing routine surveillance for recurrence, having been diagnosed with recurrence but prior to initiation of chemotherapy. . Patients from Study Arm 1 will automatically be included in Study Arm 2 as well unless they withdraw consent. Finally, patients who have been diagnosed with an ovarian cancer of acceptable histology but not yet initiated adjuvant chemotherapy are eligible for Study Arm 2.

Exclusion Criteria:

Known sarcomatous histologies
Current usage of VPA or Dex, if patient has been on these medications in the past but is not currently taking them she is still a candidate for the study. Prior use must be greater than one month for VPA. There is no "wash out" period required for DEX.
Any contraindication to dexamethasone or valproic acid such as known allergies or sensitivity
Unable to give informed consent
Pregnancy
Greater than 3 x the upper limit of normal (ULN) for alanine aminotransferase (ALT), aspartate aminotransferase (AST)
Greater than 3 x the ULN for total bilirubin (except for known cases of Gilbert's syndrome, where the levels of conjugated bilirubin must be less than 3 x the ULN)
Greater than 1.5 x the ULN for blood urea nitrogen (BUN)
Greater than 1.5 x the ULN for creatinine
Chronic or acute pancreatitis as evidenced by clinical or pathologic diagnosis
Significant acute or chronic medical, neurologic, or psychiatric illness in the subject that, in the judgment of the Investigator, could compromise subject safety, limit the subject's ability to complete the study, and/or compromise the objectives of the study
For study Arm 2, patients that are currently undergoing chemotherapy for recurrence; maintenance chemotherapy is not considered an exclusion criteria. Additionally, as noted above if a patient has not yet begun chemotherapy for recurrence or adjuvant chemotherapy for initial diagnosis they are still a candidate to be enrolled on this Study arm.

Sites / Locations

Karmanos Cancer Institute at McLaren Bay Region, Bay City
Wayne State University/Karmanos Cancer Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm I (induction)

Arm II (surveillance and recurrence)

Arm Description

Patients receive valproic acid PO BID on days -7 to -3 and QD on day -2 and dexamethasone PO QD on days -5 and -2 and BID on days -4 and -3. Patients undergo collection of serum and tissue samples for analysis via PCR and IHC at baseline, time of surgery, and 7-14 days after surgery.

Patients receive valproic acid PO BID on days -7 to -3 and QD on day -2 and dexamethasone PO QD on days -5 and -2 and BID on days -4 and -3. Patients undergo collection of serum samples for analysis via PCR and IHC at the time of clinically suspected recurrence, 2 days after completion of induction, and 7-14 days after induction.

Outcomes

Primary Outcome Measures

Arm I: To evaluate the ability to increase serum Folate Receptor (FR) levels in patients with newly diagnosed adnexal masses or ovarian cancer utilizing Dexamethasone (DEX) and Valproic Acid (VA).

FR will be measured in the serum of patients utilizing a standardized tritiated folate/charcoal binding assay pre- and post-drug administration. This will be measured to the femto-molar level. Two sided t-tests will be utilized as a baseline statistical analysis to determine the efficacy of induction in this setting.

Arm I: To evaluate the utility of serum FR to distinguish between patients with benign masses or malignancy.

Folate receptor levels in patients with benign and malignant conditions will be compared utilizing receiver operator curves for both pre- and post-induction levels to determine if soluble folate receptor can be utilized as a tumor marker in newly diagnosed adnexal masses and/or ovarian cancer. Both two-sided t tests and ROC curve analysis will be utilized in this portion of the analysis.

Arm II: To evaluate the use of the serum soluble FR as a marker for earlier detection of recurrent disease.

Patients are to be followed during surveillance period for a history of know ovarian carcinoma with serum FR in addition to CA-125. FR will again be measured in the serum of patients utilizing a standardized tritiated folate/charcoal binding assay. This will be measured to the femto-molar level. ROC curve analysis will be performed to evaluate the efficacy of baseline Folate Receptor in early detection of relapse and compared to standard tumor markers such as CA-125.

Arm II: To evaluate the ability to increase serum FR levels with DEX and VA in the setting of recurrent disease.

If recurrence is suspected, this portion of Arm 2 is meant to determine if serum levels of FR can be artificially increased in the recurrent setting utilizing DEX and VA above baseline recurrent levels. FR will be measured in the serum of patients utilizing a standardized tritiated folate/charcoal binding assay pre- and post-drug administration. This will be measured to the femto-molar level. Two side t-tests will be utilized to determine the efficacy of induction in this setting.

Secondary Outcome Measures

Arm I: To evaluate expression of FR via immunohistochemistry in primary vs. metastatic tumor sites in patients with ovarian malignancy undergoing DEX & VA induction and determine if this correlates with other known markers associated with malignancy.

Two sided independent t-tests will be performed to compare the expression of FR in primary vs metastatic tumor sites. Pearson's correlation coefficients will be calculated to evaluate the associations between serum FR and existing markers such as Ki67 and CA-125.

Arm I: To examine downstream targets of GR and FR induction in patient samples undergoing treatment with DEX and VA via global mRNA analysis and proteomic modalities.

Achieved by utilizing such techniques (but not limited to) as transcriptome analysis and whole genome Chip analysis.

Arm I: To analyze the correlation between GR level as noted by immunohistochemistry and serum FR induction efficacy with DEX and VA.

Pearson's correlation coefficients will be calculated to evaluate the associations between serum Folate receptor levels and tissue based glucocorticoid receptors.

Full Information

NCT ID

NCT02520115

First Posted

July 30, 2015

Last Updated

August 12, 2019

Sponsor

Barbara Ann Karmanos Cancer Institute

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT02520115

Brief Title

Folate Receptor in Diagnosing Ovarian Cancer Using Serum Samples From Patients With Newly Diagnosed Pelvic Mass or Previously Diagnosed Ovarian Cancer

Official Title

Study of Serum Measured Folate Receptor and Its Induction as a Biomarker in the Diagnosis and Surveillance of Ovarian Carcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

August 2019

Overall Recruitment Status

Completed

Study Start Date

August 2015 (undefined)

Primary Completion Date

September 2018 (Actual)

Study Completion Date

November 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Barbara Ann Karmanos Cancer Institute

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This pilot research trial studies folate receptor in diagnosing ovarian cancer using serum samples from patients with a newly diagnosed pelvic mass or previously diagnosed ovarian cancer. Studying samples of serum from patients with ovarian cancer in the laboratory may help understand the use of folate receptor induction as a clinical tool in initial diagnosis, surveillance, and recurrence.

Detailed Description

PRIMARY OBJECTIVES: I. To evaluate the pre- and post-induction correlation between soluble folate receptor and tumor-based receptor levels as a marker of malignancy in patients with newly diagnosed adnexal masses. (Arm I) II. To evaluate the ability to induce serum folate receptor (FR) with dexamethasone (Dex) and valproic acid (VPA) treatment in patients with newly diagnosed adnexal masses. (Arm I) III. To evaluate the use of the serum soluble FR as a marker for earlier detection of recurrent disease. (Arm II) IV. To evaluate the ability to induce FR with Dex and VPA in the setting of recurrent disease. (Arm II) SECONDARY OBJECTIVES: I. To evaluate the expression of FR in primary versus (vs.) metastatic tumor sites in patients with ovarian malignancy undergoing Dex and VPA induction and correlate expression with other markers associated with malignancy (marker of proliferation Ki-67 [Ki67], cancer antigen [CA]-125, etc.). II. To analyze the correlation between gluco-corticoid receptor (GR) levels and serum FR induction efficacy. III. To examine global, downstream targets of GR and FR induction in patient samples undergoing treatment with Dex and VPA. OUTLINE: Patients are assigned to 1 of 2 arms. ARM I (INDUCTION): Patients receive valproic acid orally (PO) twice daily (BID) on days -7 to -3 and once daily (QD) on day -2 and dexamethasone PO QD on days -5 and -2 and BID on days -4 and -3. Patients undergo collection of serum and tissue samples for analysis via polymerase chain reaction (PCR) and immunohistochemistry (IHC) at baseline, time of surgery, and 7-14 days after surgery. ARM II (SURVEILLANCE AND RECURRENCE): Patients receive valproic acid PO BID on days -7 to -3 and QD on day -2 and dexamethasone PO QD on days -5 and -2 and BID on days -4 and -3. Patients undergo collection of serum and tissue samples for analysis via PCR and IHC at the time of clinically suspected recurrence, 2 days after completion of induction, and 7-14 days after induction.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Adnexal Mass, Borderline Ovarian Epithelial Tumor, Ovarian Clear Cell Tumor, Ovarian Endometrioid Tumor, Ovarian Neoplasm, Ovarian Serous Tumor, Recurrent Ovarian Carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

50 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm I (induction)

Arm Type

Experimental

Arm Description

Arm Title

Arm II (surveillance and recurrence)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Dexamethasone

Other Intervention Name(s)

Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, Visumetazone

Intervention Description

Given PO

Intervention Type

Other

Intervention Name(s)

Laboratory Biomarker Analysis

Intervention Description

Analysis of serum and tissue samples

Intervention Type

Drug

Intervention Name(s)

Valproic Acid

Other Intervention Name(s)

Depakene, Stavzor, Valproate

Intervention Description

Given PO

Primary Outcome Measure Information:

Title

Arm I: To evaluate the ability to increase serum Folate Receptor (FR) levels in patients with newly diagnosed adnexal masses or ovarian cancer utilizing Dexamethasone (DEX) and Valproic Acid (VA).

Description

Time Frame

Up to 14 days after induction

Title

Arm I: To evaluate the utility of serum FR to distinguish between patients with benign masses or malignancy.

Description

Time Frame

Up to 14 days after surgery

Title

Arm II: To evaluate the use of the serum soluble FR as a marker for earlier detection of recurrent disease.

Description

Time Frame

Up to 14 days after induction

Title

Arm II: To evaluate the ability to increase serum FR levels with DEX and VA in the setting of recurrent disease.

Description

Time Frame

Up to 14 days after surgery

Secondary Outcome Measure Information:

Title

Description

Time Frame

Up to day 14

Title

Arm I: To examine downstream targets of GR and FR induction in patient samples undergoing treatment with DEX and VA via global mRNA analysis and proteomic modalities.

Description

Achieved by utilizing such techniques (but not limited to) as transcriptome analysis and whole genome Chip analysis.

Time Frame

Up to day 14

Title

Arm I: To analyze the correlation between GR level as noted by immunohistochemistry and serum FR induction efficacy with DEX and VA.

Description

Pearson's correlation coefficients will be calculated to evaluate the associations between serum Folate receptor levels and tissue based glucocorticoid receptors.

Time Frame

Up to day 14

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: For study Arm 1, female subjects of childbearing potential or less than 2 years postmenopausal agree to use an acceptable form of contraception from the time of signing informed consent until 30 days after study completion unless total hysterectomy performed at the time of original operation Able to provide informed consent Performance status Eastern Cooperative Oncology Group (ECOG) 0-2 Study Arm 1: primary diagnosis of a pelvic or adnexal mass of presumed gynecologic origin who is scheduled for operative resection Study Arm 2: previously diagnosed with a non-mucinous epithelial ovarian carcinoma (including serous, clear cell, and endometrioid histologies as well as borderline ovarian tumors) currently undergoing routine surveillance for recurrence, having been diagnosed with recurrence but prior to initiation of chemotherapy. . Patients from Study Arm 1 will automatically be included in Study Arm 2 as well unless they withdraw consent. Finally, patients who have been diagnosed with an ovarian cancer of acceptable histology but not yet initiated adjuvant chemotherapy are eligible for Study Arm 2. Exclusion Criteria: Known sarcomatous histologies Current usage of VPA or Dex, if patient has been on these medications in the past but is not currently taking them she is still a candidate for the study. Prior use must be greater than one month for VPA. There is no "wash out" period required for DEX. Any contraindication to dexamethasone or valproic acid such as known allergies or sensitivity Unable to give informed consent Pregnancy Greater than 3 x the upper limit of normal (ULN) for alanine aminotransferase (ALT), aspartate aminotransferase (AST) Greater than 3 x the ULN for total bilirubin (except for known cases of Gilbert's syndrome, where the levels of conjugated bilirubin must be less than 3 x the ULN) Greater than 1.5 x the ULN for blood urea nitrogen (BUN) Greater than 1.5 x the ULN for creatinine Chronic or acute pancreatitis as evidenced by clinical or pathologic diagnosis Significant acute or chronic medical, neurologic, or psychiatric illness in the subject that, in the judgment of the Investigator, could compromise subject safety, limit the subject's ability to complete the study, and/or compromise the objectives of the study For study Arm 2, patients that are currently undergoing chemotherapy for recurrence; maintenance chemotherapy is not considered an exclusion criteria. Additionally, as noted above if a patient has not yet begun chemotherapy for recurrence or adjuvant chemotherapy for initial diagnosis they are still a candidate to be enrolled on this Study arm.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ira Winer

Organizational Affiliation

Barbara Ann Karmanos Cancer Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Karmanos Cancer Institute at McLaren Bay Region, Bay City

City

Bay City

State/Province

Michigan

ZIP/Postal Code

48706

Country

United States

Facility Name

Wayne State University/Karmanos Cancer Institute

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48201

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Folate Receptor in Diagnosing Ovarian Cancer Using Serum Samples From Patients With Newly Diagnosed Pelvic Mass or Previously Diagnosed Ovarian Cancer

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