Safety and Efficacy Study of Nuc-1031 and Carboplatin Combination to Treat Recurrent Ovarian Cancer (ProGem2)

• ClinicalTrials.gov Identifier: NCT02303912
• Recruitment Status: Completed
• First Posted: December 1, 2014
• Last Update Posted: May 18, 2021
• Sponsor: Imperial College Healthcare NHS Trust
• Information provided by (Responsible Party): Imperial College Healthcare NHS Trust

Tracking Information

• First Submitted Date: October 10, 2014
• First Posted Date: December 1, 2014
• Last Update Posted Date: May 18, 2021
• Study Start Date: November 2014
• Actual Primary Completion Date: January 23, 2017 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 25, 2014): To determine the Recommended Phase II Dose (RP2D) of Nuc-1031 and carboplatin when administered in combination. [ Time Frame: 1 year ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 25, 2014)

• 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. [ Time Frame: 1 year ]
• To evaluate the objective response rate (ORR) of Nuc-1031 administered in combination with carboplatin in participants with recurrent ovarian cancer. [ Time Frame: 1 year ]
• To evaluate the clinical benefit rate (CBR) of Nuc-1031 administered in combination with carboplatin in participants with recurrent ovarian cancer. [ Time Frame: 1 year ]
• To evaluate the progression free survival (PFS) of participants with recurrent ovarian cancer treated with Nuc-1031 in combination with carboplatin. [ Time Frame: 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 [ Time Frame: 1 year ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy Study of Nuc-1031 and Carboplatin Combination to Treat Recurrent Ovarian Cancer
• Official Title: 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.
• 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.

Detailed Description

Nuc-1031 and carboplatin combination is a new experimental treatment for ovarian cancer which reappear after standard chemotherapy. Chemotherapy is the name for drug treatments to kill or control the growth of cancer cells. Although there is some evidence from laboratory and clinical studies that Nuc-1031 is effective in the treatment of ovarian cancer, it has not yet been tested in combination with another chemotherapy drug. So this combination treatment is classed as a first in human study(Phase1B). The aim of the study is to investigate whether adding Nuc-1031 to carboplatin can improve the benefits of chemotherapy.

Other purposes are to find out whether Nuc-1031 is safe to give with carboplatin, to identify the correct dose of Nuc-1031 when given with carboplatin and establish how effective the combination is at treating ovarian cancer. This study is also designed to enable us to find out whether Nuc-1031 adds further benefit, over and above that achieved by carboplatin alone, when treating ovarian cancer. and carboplatin combination will be given in six cycles. Each cycle is 3 weeks long. On first day of first week of each cycle (day1), selected study participants will receive one dose of both Nuc-1031 and Carboplatin chemotherapy. Following this, the study participant will receive a second dose of Nuc-1031 alone on first day of second week (day 8). This schedule will be repeated every 3 weeks for 6 cycles.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Recurrent Ovarian Cancer

Intervention

Drug: Nuc-1031 and Carboplatin

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)

Study Arms

Open label dose escalation

Nuc-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

Intervention: Drug: Nuc-1031 and Carboplatin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 9, 2019): 25
• Original Estimated Enrollment (submitted: November 25, 2014): 36
• Actual Study Completion Date: January 23, 2017
• Actual Primary Completion Date: January 23, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT02303912
• Other Study ID Numbers: PRO-002; 2014-002006-21 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Imperial College Healthcare NHS Trust
• Study Sponsor: Imperial College Healthcare NHS Trust
• Collaborators: Not Provided

Investigators

• Study Director: Sarah Blagden, MBBS, MRCP; University of Oxford

• PRS Account: Imperial College Healthcare NHS Trust
• Verification Date: May 2021