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

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

Trial Summary

Official Title

A Phase 1/2, Open Label, Multi-center Study of VAL-083 in Patients With Recurrent Platinum Resistant Ovarian Cancer

Status

Not yet recruiting

Condition

Ovarian Cancer

Actual Start Date

January 2018

Estimated Primary Completion Date

June 2019

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

We’re initiating a Phase 1/2, open label, multi-center study of VAL-083 in patients with recurrent platinum resistant ovarian cancer.

Detailed Info

Brief Summary

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.

Study Phase

Phase 1/Phase 2

Estimated Enrollment

80

Estimated Primary Completion Date

June 2019

Study Type

Interventional

Interventions
  • Drug: VAL-083, Dianhydrogalactitol
Sponsor

DelMar Pharmaceuticals, Inc.

Eligibility

Gender

Male & Female

18+

Age

18 years and older

≤ 2

ECOG

Performance Status

Inclusion Criteria

  1. Last dose of chemotherapy: At least 4 weeks
  2. 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).
  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:
    • Absolute neutrophil count (ANC) ≥ 1500/μL
    • Hemoglobin (HgB) ≥ 9 g/dL
    • Platelets ≥ 100,000/μL ( > 150,000/μL if prior nitrosureas)
    • 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)
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be < 2 × ULN unless liver metastases are present, in which case they must be ≤ 5 × ULN.
    • 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.
    • 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:
    • 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
    • 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.

Location

The following cities have clinical trial sites. Please check back often as locations will be updated.

Enrollment

For more information on enrollment into the current VAL-083 trial, please contact us or visit clinicaltrials.gov for location information.

Frequently Asked Questions

A Clinical Trial is a type of research study that examines how well a potential therapy works in humans.

This clinical trial was done to determine the safety and the maximal tolerated dose (MTD) of VAL-083 in patients with recurrent malignant glioma. Pharmacokinetic (PK) properties will be explored and tumor responses to treatment will be evaluated.

This clinical trial has certain criteria that a person has to meet to determine if they can participate. After you have discussed the trial with your doctor, specific tests will be done to see if you qualify for this study.

The Eastern Cooperative Oncology Group (ECOG) performance status allows patients to be classified by how their disease is progressing, how the disease affects their daily living abilities, and determine appropriate treatment and prognosis. Scores run from 0 to 5; the higher the ECOG score, the worse the survival rate for most serious illnesses.

DelMar Pharmaceuticals, Inc.is sponsoring this clinical trial.

The total number of patients enrolled in this clinical trial will be 55 subjects. This trial utilized a standard 3 + 3 dose escalation design, until the MTD or the maximum specified dose was been reached. In Phase 2, additional patients with GBM were treated at the MTD (or other selected optimum Phase 2 dose) to measure tumor responses to treatment.

Have your physician complete the contact form.

The safety and efficacy of the investigational use of this product has not been determined. There is no guarantee that the investigational use listed will be filed with and/or approved for marketing by a regulatory agency.

The safety and efficacy of the investigational use of this product has not been determined. There is no guarantee that the investigational use listed will be filed with and/or approved for marketing by a regulatory agency.