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

NCT03281681 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: DLM-17-001
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

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.

Conditions

Ovarian Cancer

Keywords

adenocarcinoma of the ovary; ovarian adenocarcinoma; ovarian cancer; cancer of the ovary; ovarian neoplasm; AO; ovarian carcinoma

Outcome Measures

Primary Outcomes (1)

• Estimate Overall Response Rate

  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)

  Every 8 weeks from Screening to achievement of either complete response (CR) or partial response (PR) for at least 6 months

Secondary Outcomes (13)

• Safety evaluation of VAL-083 for adverse events

  From Screening up to 28 days following last study treatment with VAL-083

• Efficacy evaluation of VAL-083 against CA-125 biomarker

  From Screening to achievement of either complete response (CR) or partial response (PR) for at least 6 months

• Progression-free Survival

  Every 30 days from Screening until disease progression or patient death, whichever occurs first, for at least 6 months

• Comparative Progression-free Survival

  Every 30 days from Screening until disease progression or patient death, whichever occurs first, for at least 6 months

• Duration of Response

  Every 8 weeks from Screening to achievement of either complete response (CR) or partial response (PR) for at least 6 months

Study Arms (1)

VAL-083, Dianhydrogalactitol

EXPERIMENTAL

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

Interventions

VAL-083, Dianhydrogalactitol DRUG

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.

VAL-083, Dianhydrogalactitol

Eligibility Criteria

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

You may qualify if:

• 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).
• Must be ≥18 years old.
• Histologically-confirmed initial diagnosis of adenocarcinoma of the ovary (AO), excluding clear cell, low grade serous, mucinous adenocarcinoma or carcinosarcoma.
• Subjects must have completed and failed a minimum of 2 previous lines of platinum-containing therapy (e.g., carboplatin, oxaliplatin, or cisplatin).
• Subjects may have failed up to 2 additional cytotoxic regimens that may have included platinum.
• Subjects must have had no more than 4 lines of prior drug therapy.
• If treated with bevazicumab, subjects should have completed and failed treatment.
• 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.
• 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.
• Formalin fixed, paraffin-embedded archival tumor available from the primary or recurrent cancer required.
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 and have been stable during wash-out period from prior therapy.
• 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.
• A minimum of 28 days between termination of the investigational drug and administration of VAL 083.
• Must have recovered from all prior treatment-related toxicities to Grade 1 or less.
• Laboratory values as follows at screening and within 3 days of planned first dose of therapy:

You may not qualify if:

• Subjects with clear cell, low grade serous or mucinous adenocarcinoma, or carcinosarcoma.
• 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.
• Persistent Grade ≥2 toxicity from prior cancer therapy.
• Subjects with declining ECOG performance status, defined by 1 point over a 28-day period, will be excluded.
• 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.
• 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
• Subjects with known active hepatic disease (i.e., hepatitis B or C).
• Subjects known to be HIV positive and not on stable medication or have an AIDS-related illness.
• Subjects with a known sensitivity to any of the products to be administered during treatment and assessments.

Sponsors & Collaborators

• DelMar Pharmaceuticals, Inc.: lead

Study Sites (3)

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Dianhydrogalactitol

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

Intervention Hierarchy (Ancestors)

Galactitol; Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates

Study Officials

• Bradley J Monk, M.D.

  St. Joseph's Hospital and Medical Center - Phoenix, Arizona

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 6, 2017
• First Posted: September 13, 2017
• Study Start: March 1, 2021
• Primary Completion: March 1, 2022
• Study Completion: September 1, 2022
• Last Updated: October 18, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)