Safety and Efficacy Study of Nuc-1031 and Carboplatin Combination to Treat Recurrent Ovarian Cancer
ProGem2
Phase 1B Open Label Study to Assess the Safety, Pharmacokinetics and Clinical Activity of Nuc-1031 Given on Days 1 & 8 With Carboplatin on Day 1, q3-weekly for 6 Cycles in Participants With Recurrent Ovarian Cancer.
2 other identifiers
interventional
25
1 country
1
Brief Summary
A first in human experimental treatment in which an experimental medicine,Nuc-1031, is used in combination with a standard cancer medicine, carboplatin, to treat ovarian cancer which reappear after standard cancer treatment. The aim of the trial is to determine safety, effectiveness, and clinical activity of this combination treatment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Nov 2014
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 10, 2014
CompletedStudy Start
First participant enrolled
November 1, 2014
CompletedFirst Posted
Study publicly available on registry
December 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 23, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
January 23, 2017
CompletedMay 18, 2021
May 1, 2021
2.2 years
October 10, 2014
May 17, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To determine the Recommended Phase II Dose (RP2D) of Nuc-1031 and carboplatin when administered in combination.
1 year
Secondary Outcomes (5)
To evaluate the safety and tolerability of Nuc-1031 administered in combination with carboplatin measured by adverse events (AE) and changes from baseline in vital signs, clinical laboratory parameters, and electrocardiography (ECG) assessments.
1 year
To evaluate the objective response rate (ORR) of Nuc-1031 administered in combination with carboplatin in participants with recurrent ovarian cancer.
1 year
To evaluate the clinical benefit rate (CBR) of Nuc-1031 administered in combination with carboplatin in participants with recurrent ovarian cancer.
1 year
To evaluate the progression free survival (PFS) of participants with recurrent ovarian cancer treated with Nuc-1031 in combination with carboplatin.
1 year
To evaluate Overall Best Response, utilising the evaluation criteria determined by the Gynecologic Cancer Intergroup (GCIG), combining the change in CA125 from baseline with RECIST 1.1 assessment
1 year
Study Arms (1)
Open label dose escalation
OTHERNuc-1031 IV injection on day 1 and day 8 repeated every 21 days Carboplatin IV infusion on day 1 repeated every 21 days. Dose escalation will be done using 3+3 dose escalation design
Interventions
Nuc-1031 IV injection on day 1 and day 8 repeated every 21 days Carboplatin IV infusion on day 1 repeated every 21 days (Total 6 cycles)
Eligibility Criteria
You may qualify if:
- Provision of signed written informed consent.
- Original diagnosis and/or histological confirmation of relapsed epithelial ovarian, fallopian tube or primary peritoneal cancer.
- Relapse ≤24 months from completion of platinum (carboplatin or cisplatin) or platinum-containing regimen.
- Age ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
- Measurable disease as defined by Response Evaluation Criteria In Solid Tumours (RECIST) criteria version 1.1; January 2009 and/or evaluable disease (evaluable: cytologically or radiologically detectable disease such as ascites, peritoneal deposits, or lesions which do not fulfill RECIST criteria version 1.1 for measurable disease) \[1,2\]. Participants for whom disease and response to therapy can be monitored by serum Cancer Antigen 125 (CA125) levels will also be eligible.
- Adequate bone marrow function as defined by: White Blood Cells of ≥ 3 x109/L, Absolute Neutrophil Count (ANC) of ≥ 2.0 x 109/L, platelet count of ≥ 100.0 x 109/L, and haemoglobin of ≥ 9 g/dL.
- Adequate liver function, as determined by: Serum total bilirubin ≤1.5 x Upper Limit of Normal \[(ULN), Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 x ULN, albumin ≥ 30g/L.
- Adequate renal function assessed as glomerular filtration rate(GFR) ≥ 60 mL/min using Cr51-ethylenediaminetetraacetic acid (EDTA) method.
- Ability to comply with protocol requirements.
- Participants must be postmenopausal (12 months of amenorrhea), surgically sterile or they must agree to use a physical method of contraception. Oral or injectable contraceptive agents cannot be the sole method of contraception. Participants of child-bearing potential must have a negative serum pregnancy test within seven days prior to the first study drug administration.
You may not qualify if:
- History of allergic reactions attributed to previous gemcitabine treatment.
- Previous treatment with Nuc-1031.
- History of allergic reactions attributed to previous carboplatin treatment.
- Symptomatic Central Nervous System (CNS) or leptomeningeal metastases.
- Prior chemotherapy, radiotherapy (other than short cycle of palliative radiotherapy for bone pain), or immunotherapy within 28 days of first receipt of study drug (within 6 weeks for nitrosoureas and mitomycin C). Hormone therapy within 14 days of first receipt of study drug.
- Prior toxicities from chemotherapy or radiotherapy which have not regressed to Grade ≤ 1 severity \[National Cancer Institute -Common Terminology Criteria for Adverse Events, (NCI-CTCAE) version 4.03\] except for neuropathy and alopecia.
- Another active cancer (excluding basal cell carcinoma) within the last 3 years.
- Participants with uncontrolled concomitant illness or active infection requiring IV antibiotics.
- Participants with serious illnesses, medical conditions, or other medical history, including laboratory results, which, in the investigator's opinion, would be likely to interfere with a their participation in the study, or with the interpretation of the results.
- Known Human Immunodeficiency Virus (HIV) or known active Hepatitis B or C.
- Any condition (e.g., known or suspected poor compliance, psychological instability, geographical location, etc.) that, in the judgment of the investigator, may affect the participant's ability to sign the informed consent and undergo study procedures.
- Currently pregnant, lactating or breastfeeding
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Garry Weston Cancer Centre, Hammersmith Hospital
London, W12 0HS, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Sarah Blagden, MBBS, MRCP
University of Oxford
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 10, 2014
First Posted
December 1, 2014
Study Start
November 1, 2014
Primary Completion
January 23, 2017
Study Completion
January 23, 2017
Last Updated
May 18, 2021
Record last verified: 2021-05