Clinical Trials

PRIMARY OBJECTIVES:

     I. To demonstrate the feasibility of conducting a 10-patient pilot study in asymptomatic ovarian cancer patients with cancer antigen (CA 125) elevation.

     SECONDARY OBJECTIVES:

     I. To explore whether oral gold therapy either stabilizes or lowers the CA 125 level and maintains patients in an asymptomatic state and to provide descriptive data on tumor response and duration of response.

     II. To acquire qualitative data on patients' perceptions of learning of CA 125 elevation.

     III. To explore whether immunohistochemical staining for PKC iota expression in resected tumor samples appears to be associated with clinical outcomes with auranofin.

     OUTLINE:

     Patients receive auranofin orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

     After completion of study treatment, patients are followed up every 6 months for 2 years.

PRIMARY OBJECTIVES: I. To assess the safety of administering a course of cyclophosphamide treatment followed by six subsequent monthly vaccinations with a peptide-based vaccine targeting folate receptor 1 (FR)-alpha (multi-epitope folate receptor alpha peptide vaccine). II. To assess the ability of this vaccination protocol to elicit an immune response as measured by activated FR-alpha-specific T lymphocytes or high-affinity antibodies. CORRELATIVE OBJECTIVES: I. To determine FR-alpha expression status of primary tumors when available as formalin-fixed, paraffin-embedded material and whether expression correlates with the ability to generate an immune response. II. To identify human lymphocyte antigen (HLA) class I binding peptides from FR-alpha that are recognized by lymphocytes from patients prior to and after vaccination. OUTLINE: Patients receive 100 mg cyclophosphamide orally daily for 1 week followed by a 1 week rest, and then another week of cyclophosphamide. Approximately 7-10 days after the last dose of cyclophosphamide, patients receive multi-epitope folate receptor alpha peptide vaccine intradermally (ID) on day 1. Vaccine treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 3, 6, and 12 months.

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose of the combination of ABT-888 (veliparib) and weekly topotecan (topotecan hydrochloride) in adult patients with advanced solid tumors. (Phase I) II. To identify any anti-tumor activity of this treatment combination, as assessed by objective response in patients with advanced solid tumors. (Phase I) III. To assess the confirmed response rate for patients with epithelial ovarian cancer or primary peritoneal carcinoma treated with the combination of ABT-888 and weekly topotecan. IV. To assess the toxicity of the combination of ABT-888 and weekly topotecan in patients with epithelial ovarian cancer or primary peritoneal carcinoma. (Phase II) SECONDARY OBJECTIVES: I. To identify any pharmacokinetic interactions between ABT-888 and topotecan. (Phase I and II) II. Phase I MTD: to provide preliminary view as to difference in response and toxicity based on BRCA mutation status. (Phase I) III. To determine whether topotecan stimulates adenosine diphosphate (ADP)-ribose polymer formation in circulating peripheral blood mononuclear cells. (Phase I) IV. To determine whether ABT-888 inhibits basal or topotecan-stimulated ADP-ribose polymer formation. (Phase I) V. To determine whether topotecan stimulates ADP-ribose polymer formation in circulating tumor cells and whether ABT-888 modulates this. (Phase II) VI. To assess differences in the toxicity and/or efficacy of this regimen based on BRCA 1/2 mutational status. (Phase II) VII. To determine whether pretreatment tumor cell levels of topoisomerase I, poly ADP-ribose polymerase (PARP), BRCA1, BRCA2, XRCC1, tyrosyl-deoxyribonucleic acid (DNA) phosphodiesterase 1 (TDP1), P-glycoprotein or breast cancer resistance protein (BCRP) predict response to this regimen. (Phase II) VIII. To identify, in an exploratory manner, any transcriptional profiles that may predict response to this regimen. (Phase II) OUTLINE: This is a phase I, dose escalation study of veliparib and topotecan hydrochloride followed by a phase II study. Patients receive veliparib orally (PO) on days 1-3, 8-10, and 15-17 (veliparib is omitted on days 1-3 of course 2) and topotecan hydrochloride intravenously (IV) over 30 minutes on days 2, 9, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 3 months (Phase I) or every 3 or 6 months for 5 years (Phase II).

PRIMARY OBJECTIVES: I. To estimate the progression-free survival hazard ratio of the combination of weekly paclitaxel with Reolysin (wild-type reovirus) to weekly paclitaxel alone in patients with persistent or recurrent ovarian, fallopian tube, or primary peritoneal cancer. II. To determine the frequency and severity of adverse events associated with treatment with weekly paclitaxel alone and weekly paclitaxel with REOLYSIN as assessed by CTCAE. SECONDARY OBJECTIVES: I. To estimate the progression-free survival and overall survival of patients treated with weekly paclitaxel alone and weekly paclitaxel with REOLYSIN. II. To estimate (and compare) the proportion of patients who respond to the regimen on each arm of the study (according to RECIST 1.1 with measurable patients and by CA-125 for those patients with detectible disease only). III. To characterize and compare progression-free survival and overall survival in patients with measurable disease (RECIST 1.1 criteria) and patients with detectable (non-measurable) disease. OUTLINE: This is a multicenter study. Patients are stratified according to their platinum-free interval (=< 182 days vs > 182 days) and measurable disease status (measurable vs non-measurable or detectable). Patients are randomized to 1 of 2 treatment arms ARM I: Patients receive paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15. ARM II: Patients receive paclitaxel as in arm I and wild-type reovirus IV over 1 hour on days 1-5. In both arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

This is a Phase 3 clinical trial to evaluate the efficacy and safety of the combination of EC145 and pegylated liposomal doxorubicin (PLD; available in the United States as Doxil® and outside the United States as Caelyx®) compared to PLD and placebo. Enrollment of 640 patients including approximately 500 that are folate receptor positive is planned.

     EC145 is a drug that is specifically designed to enter cancer cells via the folate vitamin receptor (FR) that is not generally found on normal cells. Experimental evidence shows that this target receptor is expressed on virtually all ovarian cancers. Early clinical evidence in a small number of Phase I participants, in a subset of participants in a completed single-arm Phase II study, and interim data from an ongoing randomized Phase 2 study (PRECEDENT) suggests that EC145 may have antitumor effect in women with platinum-resistant ovarian cancer and that EC145 alone and in combination with PLD is generally well-tolerated. This evidence suggests that EC145 may be useful as chemotherapy against platinum-resistant ovarian cancer.

     All participants will undergo imaging with the FR-targeting investigational diagnostic agent EC20 during the screening period to assess binding of the imaging agent EC20 to tumors. This non-invasive procedure will provide additional information on the utility of using EC20 imaging to identify subjects with the FR molecular "target" prior to treatment with EC145 therapy.

OBJECTIVES:

     Primary

       -  To determine whether the score on Instrumental Activities of Daily Living (IADL) obtained at time of registration is associated with the ability of patients to complete four courses of chemotherapy without dose reduction or a more than 7-day delay.

       -  To estimate by regimen the percentage of patients who are able to complete four courses of chemotherapy regardless of dose reductions and delays.

       -  To compare actual and calculated carboplatin area under the curve (AUC) in this patient population.

     Secondary

       -  To describe the percentage of patients who are entered after primary surgery versus those entered to receive primary or neoadjuvant chemotherapy, the percentage of patients who are treated with each allowed regimen, and the percentage of patients who eventually receive surgery in the primary chemotherapy group.

       -  To determine whether the need for assistance with IADLs at time of registration is associated with choice of chemotherapy regimen (in both primary chemotherapy and primary surgery patients).

       -  To explore whether age, baseline scores on the geriatric measures (functional status, nutritional status, or co-morbidity) and quality-of-life (QOL) are correlated with likelihood of completing four courses of chemotherapy without dose reduction or a more than 7-day delay.

       -  To explore reasons for and timing of dose reductions and delays.

       -  To describe toxicities, pre-/post-chemotherapy QOL, and pre-/post-chemotherapy scores on geriatric measures in this patient population.

     Tertiary

       -  To explore potential relationships of carboplatin AUC, paclitaxel clearance, and paclitaxel time above a plasma concentration of 0.05 mcM to nadir neutrophil and platelet counts during course 1 of treatment.

       -  To explore the association between baseline IADL and survival.

       -  To explore the association between IADL and the functional well-being (FWB) subscale in the Functional Assessment of Cancer Therapy - Ovary (FACT-O).

     OUTLINE: Patients receive chemotherapy comprising carboplatin, paclitaxel, and filgrastim (regimen 1) or carboplatin alone (regimen 2) every 21 days for 4 courses according to their physicians and/or patients' choice. Patients may undergo surgery and/or further chemotherapy at the discretion of treating physician.

     Patients undergo blood sample collection at baseline and periodically during course 1 for pharmacokinetic studies.

     Patients' quality of life is assessed by the Functional Assessment of Cancer Therapy - Ovary (FACT-O), the Functional Assessment of Cancer Treatment - Neurotoxicity (FACT-Ntx subscale), the Instrumental Activities of Daily Living (IADL), and the Ability to Complete Social Activity questionnaires at baseline, prior to courses 1 and 3, and then 3-6 weeks after completion of course 4. Nutritional status, such as body mass index and weight loss, and comorbidity and hearing impairment are also assessed.

This multicenter, open-label, dose-escalating study will assess the safety and efficacy of DMOT4039A in patients with unresectable pancreatic or platinum-resistant ovarian cancer. Cohorts of patients will receive multiple ascending intravenous doses of DMOT4039A. Anticipated time on study treatment is up to 1 year or until disease progression occurs.

This study is designed to determine whether an oral perioperative medication (alvimopan--a selective mu antagonist) improves bowel recovery over placebo after surgery for ovarian cancer.

The phase 1 dose escalation portion will establish the maximum tolerated dose (MTD) in patients with advanced solid tumors. Once the recommended phase 2 dose (RP2D) is established for both schedules, the phase 2 study will begin. Patients with relapsed/recurrent epithelial ovarian cancer will be randomized 1:1:1 to 3 treatment groups.