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Trial record 3 of 6 for:    val-083

A Multi-center Study of VAL-083 in Patients With Recurrent Platinum Resistant Ovarian Cancer (REPROVe)

This study is not yet open for participant recruitment.
Verified October 2017 by DelMar Pharmaceuticals, Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT03281681
First Posted: September 13, 2017
Last Update Posted: October 20, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
DelMar Pharmaceuticals, Inc.
  Purpose
This is an open label, multi-center, Phase 1/2 clinical trial in subjects with recurrent adenocarcinoma of the ovary who have been previously treated with a minimum of two courses of platinum-based chemotherapy, and up to two additional cytotoxic regimens that may also have included platinum (no more than four total lines of prior therapy), with or without bevacizumab, whose cancer has recurred within six months of the most recent platinum-based chemotherapy. All eligible subjects will receive VAL 083 i.v. in a once weekly cycle until disease progression, development of other unacceptable toxicity, death, withdrawal of consent, loss to follow-up, or Sponsor ending the study, whichever occurs first.

Condition Intervention Phase
Ovarian Cancer Drug: VAL-083, Dianhydrogalactitol Phase 1 Phase 2

Access to an investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2, Open Label, Multi-center Study of VAL-083 in Patients With Recurrent Platinum Resistant Ovarian Cancer

Resource links provided by NLM:


Further study details as provided by DelMar Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Estimate Overall Response Rate [ Time Frame: Every 8 weeks from Screening to achievement of either complete response (CR) or partial response (PR) for at least 6 months ]
    Overall number of tumor complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria or GCIG criteria using computed tomography (CT) or magnetic resonance imaging (MRI)


Secondary Outcome Measures:
  • Safety evaluation of VAL-083 for adverse events [ Time Frame: From Screening up to 28 days following last study treatment with VAL-083 ]
    Using NCI CTCAE version 4 criteria to assess frequency, severity and study drug relationship of clinically significant changes in vital signs, lab test results, EKGs or any other adverse events reported while patients are receiving treatment with VAL-083

  • Efficacy evaluation of VAL-083 against CA-125 biomarker [ Time Frame: From Screening to achievement of either complete response (CR) or partial response (PR) for at least 6 months ]
    To measure the changes in concentration of CA-125 antigen levels in blood

  • Progression-free Survival [ Time Frame: Every 30 days from Screening until disease progression or patient death, whichever occurs first, for at least 6 months ]
    Time from start of treatment until first occurrence of progression or patient death, whichever occurs first

  • Comparative Progression-free Survival [ Time Frame: Every 30 days from Screening until disease progression or patient death, whichever occurs first, for at least 6 months ]
    Progression-free Survival for VAL-083 compared to Progression-free Survival for patient's last treatment regimen received

  • Duration of Response [ Time Frame: Every 8 weeks from Screening to achievement of either complete response (CR) or partial response (PR) for at least 6 months ]
    Time from start of treatment to achievement of either complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria or GCIG criteria using computed tomography (CT) or magnetic resonance imaging (MRI)

  • Overall Survival [ Time Frame: Every 30 days from Screening until patient death or for at least 6 months, whichever occurs first ]
    Length of time from start of treatment until patient death

  • Cmax [ Time Frame: Treatment Day 1 pre-dose, then 15 ± 5 min, 30 ± 5 min, 60 ± 10 min, 120 ± 10 min, 240 ± 15 min, and 360 ± 15 min after the end of the of i.v. infusion of VAL-083 ]
    Maximum observed plasma concentration of VAL-083 in the first 10 study subjects receiving VAL-083

  • Tmax [ Time Frame: Treatment Day 1 pre-dose, then 15 ± 5 min, 30 ± 5 min, 60 ± 10 min, 120 ± 10 min, 240 ± 15 min, and 360 ± 15 min after the end of the of i.v. infusion of VAL-083 ]
    Time of maximum observed plasma concentration of VAL-083 in the first 10 study subjects receiving VAL-083

  • AUClast [ Time Frame: Treatment Day 1 pre-dose, then 15 ± 5 min, 30 ± 5 min, 60 ± 10 min, 120 ± 10 min, 240 ± 15 min, and 360 ± 15 min after the end of the of i.v. infusion of VAL-083 ]
    Area under the concentration-time curve from pre-dose (time 0) to the time of the last quantifiable concentration of VAL-083 in plasma for the first 10 study subjects receiving VAL-083

  • AUCinf [ Time Frame: Treatment Day 1 pre-dose, then 15 ± 5 min, 30 ± 5 min, 60 ± 10 min, 120 ± 10 min, 240 ± 15 min, and 360 ± 15 min after the end of the of i.v. infusion of VAL-083 ]
    Area under the concentration-time curve extrapolated to infinity for VAL-083 in plasma of the first 10 study subjects receiving VAL-083

  • Lambda z [ Time Frame: Treatment Day 1 pre-dose, then 15 ± 5 min, 30 ± 5 min, 60 ± 10 min, 120 ± 10 min, 240 ± 15 min, and 360 ± 15 min after the end of the of i.v. infusion of VAL-083 ]
    Terminal elimination rate constant determined by selection of at least 3 decreasing data points on the terminal phase of the concentration-time curve for VAL-083 in plasma of the first 10 study subjects receiving VAL-083

  • T 1/2 [ Time Frame: Treatment Day 1 pre-dose, then 15 ± 5 min, 30 ± 5 min, 60 ± 10 min, 120 ± 10 min, 240 ± 15 min, and 360 ± 15 min after the end of the of i.v. infusion of VAL-083 ]
    Terminal elimination half-life of VAL-083 in plasma of the first 10 study subjects receiving VAL-083

  • Quality of Life [ Time Frame: Every 4 weeks from Screening until disease progression, for at least 6 months ]
    Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI)


Estimated Enrollment: 80
Anticipated Study Start Date: January 2018
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: VAL-083, Dianhydrogalactitol
VAL-083 given by intravenous infusion with a starting dose of 60 mg/m2 once weekly. If this regimen is well tolerated for at least three sequential weekly treatments the patient's dose may be escalated to 67 mg/m2 i.v. If the 67 mg/m2 dose is well tolerated for at least three sequential weekly treatments the patient's dose may be escalated to 75 mg/m2 i.v. once weekly for the remainder of the study. Dosing will be conducted once per week for a total of 16 weeks.
Drug: VAL-083, Dianhydrogalactitol
VAL-083 given by intravenous infusion with a starting dose of 60 mg/m2 once weekly. If this regimen is well tolerated for at least three sequential weekly treatments the patient's dose may be escalated to 67 mg/m2 i.v. If the 67 mg/m2 dose is well tolerated for at least three sequential weekly treatments the patient's dose may be escalated to 75 mg/m2 i.v. once weekly for the remainder of the study. Dosing will be conducted once per week for a total of 16 weeks.

  Show Detailed Description

  Eligibility

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient must willingly provide written consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts. (Human protection committee approval of this protocol and consent form is required).
  2. Must be ≥18 years old.
  3. Histologically-confirmed initial diagnosis of adenocarcinoma of the ovary (AO), excluding clear cell, low grade serous, mucinous adenocarcinoma or carcinosarcoma.
  4. Subjects must have completed and failed a minimum of 2 previous lines of platinum-containing therapy (e.g., carboplatin, oxaliplatin, or cisplatin).
  5. Subjects may have failed up to 2 additional cytotoxic regimens that may have included platinum.
  6. Subjects must have had no more than 4 lines of prior drug therapy.
  7. If treated with bevazicumab, subjects should have completed and failed treatment.
  8. Subjects with BRCA mutation (positive) should have completed and failed treatment with a PARP inhibitor, or have been ineligible for treatment with a PARP inhibitor.
  9. Patient must have had documented best response, disease recurrence, and date of progression based on RECIST v1.1 or CGIG criteria within 6 months from the start of last prior platinum-based therapy.
  10. Formalin fixed, paraffin-embedded archival tumor available from the primary or recurrent cancer required.
  11. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 and have been stable during wash-out period from prior therapy.
  12. Adequate recovery from all recent surgery is required; at least 1 week must have elapsed from the time of a minor surgery; at least 21 days must have elapsed from the time of a major surgery. Must have recovered from all surgery-related toxicities to Grade 1 or less.
  13. A minimum of 28 days between termination of the investigational drug and administration of VAL 083.
  14. Must have recovered from all prior treatment-related toxicities to Grade 1 or less.
  15. Laboratory values as follows at screening and within 3 days of planned first dose of therapy:

    1. Absolute neutrophil count (ANC) ≥ 1500/μL
    2. Hemoglobin (HgB) ≥ 9 g/dL
    3. Platelets ≥ 100,000/μL ( > 150,000/μL if prior nitrosureas)
    4. Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance > 60 mL/min (measured or calculated by the Cockcroft-Gault formula) (Cockcroft & Gault, 1976)
    5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be < 2 × ULN unless liver metastases are present, in which case they must be ≤ 5 × ULN.
    6. Total bilirubin < 1.5 × the institutional ULN, unless the patient has documented conjugated bilirubin disorder such as Gilbert's syndrome. Subjects with known Gilbert's disease who have serum bilirubin ≤ 3 × ULN (NCI CTCAE v4.03 Grade 2) may be enrolled.
    7. International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN
  16. Heart-rate corrected QT interval (QTc) < 450 msec on screening EKG.
  17. No clinically significant cardiac conduction disorder on screening.
  18. Subjects must be willing and able to comply with scheduled visits, treatment plan, and laboratory tests and be accessible for follow-up.

Exclusion Criteria:

  1. Subjects with clear cell, low grade serous or mucinous adenocarcinoma, or carcinosarcoma.
  2. Current history of neoplasm other than the entry diagnosis. Subjects with previous cancers treated and cured with local therapy alone may be considered with approval of the Medical Monitor.
  3. Persistent Grade ≥2 toxicity from prior cancer therapy.
  4. Subjects with declining ECOG performance status, defined by 1 point over a 28-day period, will be excluded.
  5. Concurrent severe, intercurrent illness including, but not limited to unstable systemic disease, including ongoing or active infection, uncontrolled hypertension, serious cardiac arrhythmia requiring medication, or psychiatric illness/social situations that would limit compliance with study requirements.
  6. Any of the following cardiac conditions:

    1. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, and/or stenting up to 12 weeks before initiation of treatment with VAL-083
    2. Class III or IV heart failure as defined by the New York Heart Association functional classification system up to 6 months before initiation of treatment with VAL-083
  7. Subjects with known active hepatic disease (i.e., hepatitis B or C).
  8. Subjects known to be HIV positive and not on stable medication or have an AIDS-related illness.
  9. Subjects with a known sensitivity to any of the products to be administered during treatment and assessments.
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT03281681


Contacts
Contact: Lorena M Lopez, B.S. 925-292-8360 llopez@solsentinel.com
Contact: John Langlands, Ph.D. 604-629-5989 jlanglands@delmarpharma.com

Locations
United States, Arizona
St. Joseph's Hospital and Medical Center Not yet recruiting
Phoenix, Arizona, United States, 85013
Contact: Bradley J Monk, M.D.    602-406-7730    bradley.monk@chw.edu   
United States, Michigan
Henry Ford Hospital Not yet recruiting
Detroit, Michigan, United States, 48202
Contact: Ding Wang, M.D., Ph.D.    800-436-7936      
United States, Tennessee
Sarah Cannon Research Institute Not yet recruiting
Nashville, Tennessee, United States, 37203
Contact: Howard A Burris, M.D.    615-320-5090      
Sponsors and Collaborators
DelMar Pharmaceuticals, Inc.
Investigators
Principal Investigator: Bradley J Monk, M.D. St. Joseph's Hospital and Medical Center - Phoenix, Arizona
  More Information

Responsible Party: DelMar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03281681     History of Changes
Other Study ID Numbers: DLM-17-001
First Submitted: September 6, 2017
First Posted: September 13, 2017
Last Update Posted: October 20, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: The Clinical Study Report for this trial will be prepared and provided to the U.S. FDA as required by applicable regulatory requirement(s). Each participating trial investigator will be provided a copy of their patient data captured in the database for this trial.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by DelMar Pharmaceuticals, Inc.:
adenocarcinoma of the ovary
ovarian adenocarcinoma
ovarian cancer
cancer of the ovary
ovarian neoplasm
AO
ovarian carcinoma

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Dianhydrogalactitol
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents