Overview

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

Status:
Withdrawn
Trial end date:
2022-09-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
DelMar Pharmaceuticals, Inc.
Treatments:
Dianhydrogalactitol
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.