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

NCT02903771 | Completed Phase 1 Results DMC

• 1 other identifier: NVGN-002-101
• Study Type: interventional
• Target: 32
• Locations: 2 countries
• Sites: 6

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.

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms; Peritoneal Neoplasms

Keywords

Cantrixil; Intraperitoneal

Outcome Measures

Primary Outcomes (4)

• Determination of the Maximum Tolerated Dose (MTD)

  Determination of the MTD: At each dose level, the number and proportion of patients in the MTD population who experience a dose-limiting toxicity (DLT) during the DLT evaluation period (Cycle 1/Part A) of Cantrixil using standard safety monitoring assessments when administered as a monotherapy. The MDT was the dose level below the cohort in which 1 or more patients had experienced a DLT.

  During Cycle 1 (21 days)

• Pharmacokinetic Profile

  Mean plasma concentration

  Cycle 1, Day 1 (Monotherapy)

• Pharmacokinetic Profile

  Mean plasma concentration

  Cycle 3, Day 1 (Cantrixil plus chemotherapy)

• Pharmacokinetic Profile

  Mean plasma concentration

  Cycle 3, Day 8 (Cantrixil plus chemotherapy)

Secondary Outcomes (4)

• Disease Response

  Baseline to End of Study (maximum 36 weeks)

• Progression Free Survival

  Baseline to End of Study (maximum 36 weeks)

• Paracentesis Events

  Baseline to End of Study (maximum 36 weeks)

• CA-125 Level

  Baseline and End of Therapy (maximum 36 weeks)

Other Outcomes (4)

• Clonogenicity of Circulating Epithelial Tumour Cells (CETC)

  Baseline, End of Monotherapy (up to 6 weeks), End of Combination Therapy (up to 24 weeks)

• Enumeration of Circulating Epithelial Tumour Cells (CETC)

  Baseline, End of Monotherapy (up to 6 weeks), End of Combination Therapy (up to 24 weeks)

• Expression of Stem Cell Markers: Aldehyde Dehydrogenase (ALDH)

  Baseline, End of Monotherapy (up to 6 weeks)

Study Arms (1)

Part A and Part B

EXPERIMENTAL

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; Drug: Part B: Expansion Cohort of Cantrixil

Interventions

Part A: Dose Escalation of Cantrixil DRUG

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.

Also known as: TRX-E-002-1 in 20% SBECD

Part A and Part B

Part B: Expansion Cohort of Cantrixil DRUG

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.

Also known as: TRX-E-002-1 in 20% SBECD

Part A and Part B

Eligibility Criteria

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

You may qualify if:

• 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.
• Patients must be female and at least 18 years old.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

You may not qualify if:

• 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.
• Patients must not have had major surgery within 4 weeks prior to screening.
• 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.
• 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.
• 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
• 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.
• 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.
• Patients with a known history of hepatitis B or C.
• Patients known to have tested positive for human immunodeficiency virus (HIV)
• Patients with a known hypersensitivity to or serious reaction to benzopyrans are excluded.

Sponsors & Collaborators

• Kazia Therapeutics Limited: lead

Study Sites (6)

Peggy and Charles Stephenson Cancer Center, OU Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Lifespan Cancer Institute, Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Mary Crowley Cancer Research Center

Dallas, Texas, 75230, United States

Location

Westmead Adults Hospital

Westmead, New South Wales, 2145, Australia

Location

ICON Cancer Care

South Brisbane, Queensland, 4101, Australia

Location

Flinders Medical Centre

Adelaide, South Australia, Australia

Location

Related Publications (1)

• Coward JI, Barve MA, Kichenadasse G, Moore KN, Harnett PR, Berg D, Garner JS, Dizon DS. Maximum Tolerated Dose and Anti-Tumor Activity of Intraperitoneal Cantrixil (TRX-E-002-1) in Patients with Persistent or Recurrent Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer: Phase I Study Results. Cancers (Basel). 2021 Jun 26;13(13):3196. doi: 10.3390/cancers13133196.

  PMID: 34206826 RESULT

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms; Peritoneal Neoplasms

Interventions

4-(para-hydroxyphenyl)-7,4'-dihydroxy-3',5'-dimethoxy-8-methylisoflavan

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; Fallopian Tube Diseases; Abdominal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases

Limitations and Caveats

Small numbers of subjects analysed limit the data available for exploratory endpoints (circulating epithelial tumour cells, expression of stem cell markers, CD44 and aldehyde dehydrogenase).

Results Point of Contact

• Title: Jeremy Simpson
• Organization: Kazia Therapeutics Ltd

Jeremy.simpson@kaziatherapeutics.com

+61 400410974

Study Officials

• A/Prof Jermaine (Jim) Coward, MBBS FRACP PhD

  ICON Cancer Care, Queensland, Australia

  PRINCIPAL INVESTIGATOR

• Dr Don Dizon, MD, FACP

  Lifespan Cancer Institute, Rhode Island, USA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2016
• First Posted: September 16, 2016
• Study Start: December 5, 2016
• Primary Completion: March 24, 2020
• Study Completion: March 24, 2020
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); AU (3)