Clinical Trial - NCT03428958

A Safety Study of NUC-3373 in Combination With Standard Agents Used in Colorectal Cancer Treatment

Recruiting

Sponsor: NuCana plc

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03428958

Protocol Info

Short Description: NUC-3373 IN COLORECTAL CANCER
Long Description: A Phase Ib open label study to assess the safety and pharmacokinetics of NUC-3373, a nucleotide analogue, given in combination with standard agents used in colorectal cancer treatment
MGH Status: IRB Open/MGH Pending
Sponsor: NuCana plc
Disease Program: GI

Next Steps


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Purpose

This is a two-part study of NUC-3373 administered every 2 weeks as an intravenous infusion, in separate combinations with leucovorin, oxaliplatin, oxaliplatin + bevacizumab, oxaliplatin + panitumumab, irinotecan, and irinotecan + cetuximab. The primary objective is to identify a recommended dose for NUC-3373 when combined with these agents.
Condition Title Intervention Phase
Colorectal Cancer Colorectal Neoplasms Colorectal Carcinoma Colorectal Tumors Neoplasms, Colorectal NUC-3373 + leucovorin NUC-3373 NUC-3373 + oxaliplatin NUC-3373 + oxaliplatin + bevacizumab NUC-3373 + oxaliplatin + panitumumab NUC-3373 + irinotecan NUC-3373 + irinotecan + cetuximab Phase 1
Study Type Interventional
Official Title A Phase Ib Open Label Study to Assess the Safety and Pharmacokinetics of NUC-3373, a Nucleotide Analogue, Given in Combination With Standard Agents Used in Colorectal Cancer Treatment

Primary Outcome Measures

Number of patients reporting treatment-emergent adverse events [Time Frame: 28 days] [Designated as safety issue: ]

Number of patients with treatment-emergent clinically significant changes in laboratory parameters, ECG changes, or changes in physical examinations [Time Frame: 28 days] [Designated as safety issue: ]


Secondary Outcome Measures

Tolerability of NUC-3373 in each combination cohort measured by dose intensity in Cycle 1 [Time Frame: 28 days] [Designated as safety issue: ]

Estimated Enrollment: 62
Study Start Date: October 2018
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: October 2019
Arms Assigned Interventions

Experimental:NUC-3373+ leucovorin

Cohort 1a: NUC-3373 administered intravenously (IV) followed by a 2-week washout period. Then, LV 400 mg/m2 IV over 2 hours prior to each NUC-3373 infusion and NUC-3373 administered IV every 2 weeks.
Drug:NUC-3373 + leucovorin
NUC-3373 + leucovorin

Experimental:NUC-3373

Cohort 1b: LV 400 mg/m2 administered IV over 2 hours prior to NUC-3373 infusion followed by a 2-week washout period. Then, NUC-3373 administered IV every 2 weeks.
Drug:NUC-3373
NUC-3373

Experimental:NUC-3373 + oxaliplatin

Cohort 2a: NUC-3373 administered every 2 weeks in combination with oxaliplatin (85 mg/m2). Leucovorin may also be administered with this combination, depending on data from Part 1.
Drug:NUC-3373 + oxaliplatin
NUC-3373 + oxaliplatin

Experimental:NUC-3373 + oxaliplatin + bevacizumab

Cohort 2b: NUC-3373 administered every 2 weeks in combination with oxaliplatin (85 mg/m2) and bevacizumab (5 mg/kg). Leucovorin may also be administered with this combination, depending on data from Part 1.
Drug:NUC-3373 + oxaliplatin + bevacizumab
NUC-3373 + oxaliplatin + bevacizumab

Experimental:NUC-3373 + oxaliplatin + panitumumab

Cohort 2c: NUC-3373 administered every 2 weeks in combination with oxaliplatin (85 mg/m2) and panitumumab (6 mg/kg). Leucovorin may also be administered with this combination, depending on data from Part 1.
Drug:NUC-3373 + oxaliplatin + panitumumab
NUC-3373 + oxaliplatin + panitumumab

Experimental:NUC-3373 + irinotecan

Cohort 3a: NUC-3373 administered every 2 weeks in combination with irinotecan (180 mg/m2). Leucovorin may also be administered with this combination, depending on data from Part 1.
Drug:NUC-3373 + irinotecan
NUC-3373 + irinotecan

Experimental:NUC-3373 + irinotecan + cetuximab

Cohort 3b: NUC-3373 administered every 2 weeks in combination with irinotecan (180 mg/m2) and cetuximab 400 mg/m2 (first dose) and 250 mg/m2 (subsequent doses). Cetuximab is administered weekly. Leucovorin may also be administered with this combination, depending on data from Part 1.
Drug:NUC-3373 + irinotecan + cetuximab
NUC-3373 + irinotecan + cetuximab

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Inclusion Criteria:

1. Provision of signed written informed consent.

2. Have histological confirmation of locally advanced/unresectable or metastatic colorectal cancer, with evidence of disease recurrence.

3. Have relapsed on or after at least at least two prior lines of therapy for locally advanced/unresectable or metastatic colorectal cancer. One prior line of therapy must be an oxaliplatin + 5-FU containing regimen and one prior line of therapy must be an irinotecan + 5-FU containing regimen.

4. Age ≥18 years.

5. ECOG Performance status 0 or 1.

6. Measurable disease as defined by RECIST.

Exclusion Criteria:

1. Prior history of hypersensitivity or current contraindications to 5-FU or capecitabine or the combination agent to be used.

2. History of allergic reactions attributed to the components of the diluents used with NUC-3373.

3. Symptomatic CNS or leptomeningeal metastases.

4. Prior chemotherapy, radiotherapy (other than short cycle of palliative radiotherapy for bone pain), treatment with a VEGF inhibitor, EGF inhibitor or immunotherapy within 21 days of first receipt of study drug.

5. Residual toxicities from chemotherapy or radiotherapy, which have not regressed to Grade ≤1 severity (CTCAE v4.03), except for alopecia. In Cohorts 1a, 1b, 3a, and 3b, residual Grade 2 neuropathy is allowed.

6. History of another malignancy diagnosed within the past 5 years, with the exception of adequately treated non-melanoma skin cancer curatively treated carcinoma in situ of the cervix or ductal carcinoma in situ (DCIS) of the breast. Patients with previous invasive cancers are eligible if treatment was completed more than 5 years prior to initiating the current study treatment, and the patient has had no evidence of recurrence since then.

7. Presence of active bacterial or viral infection including Herpes Zoster or chicken pox.

8. Presence of any serious uncontrolled concomitant illness, serious illness, medical condition, or other medical history, including laboratory results, which, in the Investigator's opinion, would be likely to interfere with their participation in the study, or with the interpretation of the results.

9. Known HIV positive or known active hepatitis B or C.

10. Any condition (e.g. known or suspected poor compliance, psychological instability, geographical location, etc.) that, in the judgment of the Investigator, may affect the patient's ability to sign the informed consent and undergo study procedures.

11. Currently pregnant, lactating or breastfeeding.

12. QTc interval >450 milliseconds for males and >470 milliseconds for females.

13. Concomitant use of drugs known to prolong QT/QTc interval.

14. Have received a live vaccination within four weeks of first planned dose of study medication.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03428958

Locations

  • United States, Tennessee
    • Vanderbilt University Nashville, Tennessee, United States, 37232
  • United States, Washington
    • Seattle Cancer Center Seattle, Washington, United States, 98109-1023
  • United Kingdom,
    • The Beatson West of Scotland Cancer Centre Glasgow, , United Kingdom, G12 0YN
    • University of Oxford Oxford, , United Kingdom, OX3 7LE

Sponsors and Collaborators

NuCana plc

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03428958
Other Study ID Numbers: 2017-002062-53
Study First Received:
Last Updated:
Health Authority:

Keywords provided by NuCana plc:

Relapsed metastatic adenocarcinoma of colon/rectum

Additional relevant MeSH terms:

Colorectal Neoplasms

Neoplasms

Leucovorin

Bevacizumab

Cetuximab

Panitumumab

Oxaliplatin

Irinotecan

Levoleucovorin

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on September 03, 2020