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

NCT02520115 | Completed Phase 1 DMC

• 4 other identifiers: 2015-024NCI-2015-010391504013983P30CA022453
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Outcome Measures

Primary Outcomes (4)

• 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.

  Up to 14 days after induction

• 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.

  Up to 14 days after surgery

• 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.

  Up to 14 days after induction

• 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.

  Up to 14 days after surgery

Secondary Outcomes (3)

• 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.

  Up to day 14

• 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.

  Up to day 14

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

  Up to day 14

Study Arms (2)

Arm I (induction)

EXPERIMENTAL

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.

Drug: Dexamethasone; Other: Laboratory Biomarker Analysis; Drug: Valproic Acid

Arm II (surveillance and recurrence)

EXPERIMENTAL

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.

Drug: Dexamethasone; Other: Laboratory Biomarker Analysis; Drug: Valproic Acid

Interventions

Dexamethasone DRUG

Given PO

Also known as: 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

Arm I (induction); Arm II (surveillance and recurrence)

Laboratory Biomarker Analysis OTHER

Analysis of serum and tissue samples

Arm I (induction); Arm II (surveillance and recurrence)

Valproic Acid DRUG

Given PO

Also known as: Depakene, Stavzor, Valproate

Arm I (induction); Arm II (surveillance and recurrence)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Barbara Ann Karmanos Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Karmanos Cancer Institute at McLaren Bay Region, Bay City

Bay City, Michigan, 48706, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Valproic Acid

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Ira Winer

  Barbara Ann Karmanos Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 30, 2015
• First Posted: August 11, 2015
• Study Start: August 1, 2015
• Primary Completion: September 1, 2018
• Study Completion: November 1, 2018
• Last Updated: August 14, 2019

Record last verified: 2019-08

Locations

US (2)