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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02903771
Recruitment Status : Completed
First Posted : September 16, 2016
Last Update Posted : April 20, 2020
Information provided by (Responsible Party):
Kazia Therapeutics Limited

Brief 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.

Condition or disease Intervention/treatment Phase
Ovarian Neoplasms Fallopian Tube Neoplasms Peritoneal Neoplasms Drug: Part A: Dose Escalation of Cantrixil Drug: Part B: Expansion Cohort of Cantrixil Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Intra-peritoneal Cantrixil in Patients With Persistent or Recurrent Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer.
Study Start Date : November 2016
Actual Primary Completion Date : March 24, 2020
Actual Study Completion Date : March 24, 2020

Arm Intervention/treatment
Experimental: Part A and Part B

Part A (Dose Escalation):

Part A is a Dose Escalation study to determine the Maximum Tolerated Dose of Cantrixil as a monotherapy.

The tolerance of Cantrixil in combination with standard chemotherapy agents will also be examined.

Part B (Expansion Cohort):

An expansion cohort of an additional 12 patients will be recruited at the MTD.

Drug: Part A: Dose Escalation of Cantrixil

Cantrixil will be administered via the intraperitoneal route only. The dose of study drug that each participant will receive will depend on how far the study has progressed when the participant enrols. There are 9 potential doses of Cantrixil, they are 0.06, 0.12, 0.24 (starting dose), 0.6, 1.25, 2.5, 5, 10, or 20 mg/kg. The dose each participant receives will remain the same during the study, unless it needs to be reduced for safety reasons. The dose will not be increased.

Each participant will receive the study drug once a week during the first two cycles; each cycle is 21-days (three weeks); the MTD will be determined during Cycle 1 only. If after two cycles of monotherapy, the patient tolerates Cantrixil adequately, they may continue to receive Cantrixil once a week and will also begin combination chemotherapy for another 6 cycles. Participants will receive no more than 8 cycles of study drug.

Other Name: TRX-E-002-1 in 20% SBECD

Drug: Part B: Expansion Cohort of Cantrixil
Once the MTD has been established, an expansion cohort will be recruited at the MTD. An additional 12 patients will be recruited in this cohort on top of those recruited in Part A at the MTD. These patients will be subjected to the same intervention described in Part A with 2 cycles of monotherapy followed by up to 6 cycles of combination therapy.
Other Name: TRX-E-002-1 in 20% SBECD

Primary Outcome Measures :
  1. Determination of the Maximum Tolerated Dose (MTD) [ Time Frame: During Cycle 1 (21 days) ]
    Determination of the MTD of Cantrixil using standard safety monitoring assessments when administered as a monotherapy.

  2. Pharmacokinetic (PK) profile of Cantrixil after intra-peritoneal (IP) administration [ Time Frame: 0-24 hours after administration ]
    Description of the PK of Cantrixil when administered as a monotherapy and in combination with standard chemotherapy agent(s)

Secondary Outcome Measures :
  1. Time to Progression (TTP) [ Time Frame: Baseline to End of Study (maximum 36 weeks) ]
    TTP will be measured as the time from treatment start until objective tumour disease progression as defined by RECIST version 1.1 and/or GCIG criteria, but does not include deaths.

  2. Time to Paracentesis [ Time Frame: Baseline to End of Study (maximum 36 weeks) ]
    The time to paracentesis will be measured as the time from treatment initiation until the next paracentesis event for ascites.

  3. Volume of Malignant Ascites [ Time Frame: Baseline to End of Study (maximum 36 weeks) ]
    The volume of abdominal fluid will be measured by estimating the volume of malignant ascites drained at each paracentesis event.

  4. Disease Response [ Time Frame: Baseline to End of Study (maximum 36 weeks) ]
    Disease response will be measured using RECIST version 1.1 criteria; during Follow-up, response may be also assessed using the Gynecological Cancer Intergroup (GCIG) response criteria that incorporates CA-125 measurements

  5. CA-125 level [ Time Frame: Baseline to End of Study (maximum 36 weeks) ]
    Concentration of CA-125 in peripheral blood will be assayed in local laboratories using locally validated assays at baseline and then weekly during treatment, at the End of Therapy and during Follow-up.

Other Outcome Measures:
  1. Tolerance of Increased Dose Frequency [ Time Frame: Baseline to End of Study (maximum 36 weeks) ]
    Determination of the optimum dose and administration schedule (i.e. weekly vs twice weekly administration) using standard safety monitoring assessments, PK measurements and tolerability of delivery in the study centre.

  2. Enumeration of Circulating Epithelial Tumour Cells (CETC) [ Time Frame: Baseline, End of Monotherapy (up to 6 weeks), End of Combination Therapy (up to 24 weeks) ]
    Enumeration of CETC in peripheral blood and malignant ascites (if present) will be assayed using the MAINTRAC® CETC Count method by Genostics or similar methodology.

  3. Clonogenicity of Circulating Epithelial Tumour Cells (CETC) [ Time Frame: Baseline, End of Monotherapy (up to 6 weeks), End of Combination Therapy (up to 24 weeks) ]
    Clonogenicity of CETCs in peripheral blood and malignant ascites (if present) will be measured using the MAINTRAC® Tumour Sphere Units assay by Genostics or similar methodology.

  4. Expression of Stem Cell Markers [ Time Frame: Baseline, End of Monotherapy (up to 6 weeks), End of Combination Therapy (up to 24 weeks) ]
    Expression of stem cell markers CD44 and ALDH1 in the isolated colonies will be measured using fluorescein isothiocyanate-labelled (FITC-labelled) or alternatively labelled antibodies and scanning fluorescent microscopy techniques.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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 ( 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02903771

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United States, Oklahoma
Peggy and Charles Stephenson Cancer Center, OU Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Rhode Island
Lifespan Cancer Institute, Rhode Island Hospital
Providence, Rhode Island, United States, 02903
United States, Texas
Mary Crowley Cancer Research Center
Dallas, Texas, United States, 75230
Australia, New South Wales
Westmead Adults Hospital
Westmead, New South Wales, Australia, 2145
Australia, Queensland
ICON Cancer Care
South Brisbane, Queensland, Australia, 4101
Australia, South Australia
Flinders Medical Centre
Adelaide, South Australia, Australia
Sponsors and Collaborators
Kazia Therapeutics Limited
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Principal Investigator: A/Prof Jermaine (Jim) Coward, BSc, MBBS, PhD, MRCP, FRACP ICON Cancer Care, Queensland, Australia
Principal Investigator: Dr Don Dizon, MD, FACP Lifespan Cancer Institute, Rhode Island, USA
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Responsible Party: Kazia Therapeutics Limited Identifier: NCT02903771    
Other Study ID Numbers: NVGN-002-101
First Posted: September 16, 2016    Key Record Dates
Last Update Posted: April 20, 2020
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Kazia Therapeutics Limited:
Additional relevant MeSH terms:
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Ovarian Neoplasms
Fallopian Tube Neoplasms
Peritoneal Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
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
Fallopian Tube Diseases
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases