Phase I Study of Cantrixil in Patients With Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer.

Summary

The main purpose of this study is to determine the safety and feasibility of weekly intra-peritoneal administration of Cantrixil to women with persistent or recurrent ovarian cancer, Fallopian tube cancer or primary peritoneal cancer. The study also aims to determine the maximum tolerated dose of Cantrixil in these patients when administered as a monotherapy or a combination therapy.

Key Facts

Interventions

Conditions

Eligibility

Inclusion Criteria:

1. Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer. The original diagnosis must be verified by a histology report. All histological sub-types and all grades of disease are eligible to participate; grade, histological sub-type and breast cancer susceptibility gene (BRCA) status must be recorded at study entry.
2. Patients must be female and at least 18 years old.
3. Patients with malignant ascites are eligible to participate; paracentesis will be conducted before the administration of Cantrixil. Drainage of the maximum volume of ascites necessary for symptomatic relief should be performed according to local standard operating procedures before administration of Cantrixil.
4. Patients must have completed at least two (2) or more prior therapies (including adjuvant therapy) for their ovarian, Fallopian tube or primary peritoneal cancer prior to participation in the current study; all prior therapies must be recorded at baseline. Patients that have received prior intraperitoneal therapy are eligible for this study.
5. Patients must have platinum-resistant relapsed disease, platinum refractory disease, or have documented intolerance to platinum therapy. Patients will not be eligible based on rising CA-125 levels alone, patients must have other clinical symptoms (such as malignant ascites) or radiological tumour measurements that support disease recurrence or progression.
6. At least 4 weeks must have passed from any previous therapy and any toxicities from prior therapies (6 weeks for bevacizumab, nitrosoureas or mitomycin C treatment) must have resolved to less than or equal to Common Terminology Criteria for Adverse Events (CTCAE version 4.03) Grade 1 with the exception of alopecia, Grade 2 prior platinum-therapy related neuropathy and Grade 2 anaemia.
7. Patients must have a performance status of Eastern Cooperative Oncology Group (ECOG) 0 to 2 and, in the Investigator's opinion, be able to complete at least a major part of the study.
8. Patients must be willing and able to undergo insertion of a port or catheter for intraperitoneal access; the type of port or catheter used will be recorded.
9. Patients may have measurable or non-measurable disease; disease response and progression will be measured and assessed according to RECIST version 1.1 criteria using contrast CT, MRI and CA 125 measurements.
10. Patients must have acceptable hepatic and marrow function as defined below:

    * Absolute neutrophil count \>1.5 x 109/L
    * Platelets \>100 x 109/L
    * Total bilirubin; \<2.5 times the institutional upper limit of normal (ULN)
    * Haemoglobin (Hb) of \>10 g/dL; patients with Hb \>9g/dL will be considered for this study if they have not received a transfusion or other bone marrow support. Patients with Hb \>10 g/dL that have received a recent transfusion will only be eligible if there has been a wash-out period of 7 days for rhesus factor and 10 days for platelet transfusions, respectively.
    * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) ≤2.5 x institutional ULN.
    * Serum creatinine \<1.5 x ULN
    * Prothrombin time (PT) or international normalised ratio (INR) ≤1.5 x ULN and activated partial thromboplastin time (aPTT) ≤1.5 x ULN if not on anticoagulation treatments.
11. Patients must be willing and able to comply with all study requirements, including treatment timing and/or nature of required assessments and treatment at designated study centre.
12. Each participant must be adequately informed about the purpose of the study; potential benefits and risks; their right to refuse participation or to withdraw consent at any time; institutional affiliation and potential competing interests of the researcher; and sources of study funding and have signed and dated a written informed consent form.

Exclusion Criteria:

1. Patients who have had chemotherapy, biologic therapy, immunotherapy, or radiotherapy within 4 weeks (6 weeks for bevacizumab, nitrosoureas or mitomycin C) prior to entering the study.
2. Patients must not have had major surgery within 4 weeks prior to screening.
3. Patients may not have received any other investigational medicinal products (IMPs) or participated in any other interventional clinical research studies within 3 months of the first Cantrixil administration.
4. Patients receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450 (CYP)1A2, CYP2B6 and CYP3A4 or those substances with narrow therapeutic index are not to be enrolled. These compounds are prohibited from screening until completion of end of therapy or first post-treatment follow-up visit. For a list of prohibited medications see the University of Indiana Clinical Pharmacology Department's P450 Drug Interaction Table (http://medicine.iupui.edu/clinpharm/ddis/main-table/). Note: the use of paclitaxel is allowed, but only 24 hours after Cantrixil administration.
5. Patients at high risk of bowel perforation are excluded, including but not limited to any one or more of the following;

   * Patients with a recent history (previous 12 months) of bowel obstruction prior to study entry
   * Patients with CT scans that suggest invasion of bowel by tumour
   * Patients with symptoms to suggest impending bowel obstruction
   * Patients with prior whole abdominal radiotherapy
   * Patients with chronic inflammatory bowel diseases such as Crohn's disease or ulcerative colitis
6. Patients may not have uncontrolled or severe systemic diseases or psychiatric conditions, which in the treating physician's opinion makes it unsafe for the patient to participate in the study or would hinder compliance with the protocol. Screening for chronic conditions is not required.
7. Patients that are pregnant, lactating, or unable to adopt adequate contraception are excluded. Women of childbearing potential must have a negative pregnancy test within 7 days prior to screening.
8. Patients with a known history of hepatitis B or C.
9. Patients known to have tested positive for human immunodeficiency virus (HIV)
10. Patients with a known hypersensitivity to or serious reaction to benzopyrans are excluded.

Outcome Measures

Locations

Linked Diseases