Clinical Trials /

A Study to Investigate Fadraciclib (CYC065), in Subjects With Advanced Solid Tumors and Lymphoma

NCT04983810

Description:

This is a 2-part, phase 1/2, open-label, multicenter study designed to evaluate the safety, tolerability, PK, pharmacodynamics, PGx, and efficacy of fadraciclib administered orally BID. This study consists of Phase 1 and Phase 2 components in subjects with advanced solid tumors and lymphoma who have progressed despite having standard therapy or for which no standard therapy exists.

Related Conditions:
  • Biliary Tract Carcinoma
  • Breast Carcinoma
  • Cancer
  • Colorectal Carcinoma
  • Endometrial Carcinoma
  • Hepatocellular Carcinoma
  • Lymphoma
  • Ovarian Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study to Investigate Fadraciclib (CYC065), in Subjects With Advanced Solid Tumors and Lymphoma
  • Official Title: A Phase 1/2, Open-label, Multicenter Study to Investigate the Safety, Pharmacokinetics, and Efficacy of Fadraciclib (CYC065), an Oral CDK 2/9 Inhibitor, in Subjects With Advanced Solid Tumors and Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: CYC065-101
  • NCT ID: NCT04983810

Conditions

  • Solid Tumor, Adult
  • Lymphoma

Interventions

DrugSynonymsArms
FadraciclibCYC065Phase I Dose escalation

Purpose

This is a 2-part, phase 1/2, open-label, multicenter study designed to evaluate the safety, tolerability, PK, pharmacodynamics, PGx, and efficacy of fadraciclib administered orally BID. This study consists of Phase 1 and Phase 2 components in subjects with advanced solid tumors and lymphoma who have progressed despite having standard therapy or for which no standard therapy exists.

Detailed Description

      Phase 1 part of the study will consist of a dose-escalation and a dose-finding component .

      Phase 2 will enroll subjects with locally advanced, recurrent, or metastatic, histologically
      confirmed advanced solid tumors or lymphoma, who have failed all standard therapies or for
      whom standard therapy does not exist, into 8 groups:

      Group 1: Endometrial or Ovarian cancer

      Group 2: Biliary tract cancer

      Group 3: HCC

      Group 4: Breast cancer, meeting any of the following criteria:

        -  HER-2 refractory MBC

        -  HR positive, HER-2 negative, MBC post-CDK4/6 inhibitor

        -  Triple-negative breast cancer (TNBC)

      Group 5: B-cell lymphoma

      Group 6: T-cell lymphoma (CTCL and PTCL)

      Group 7: mCRC, including KRAS mutated mCRC

      Group 8: Basket cohort: Tumor types suspected to have a related mechanism of action such as
      MCL1, MYC or CCNE amplification/overexpression not included in previous groups.
    

Trial Arms

NameTypeDescriptionInterventions
Phase I Dose escalationExperimentalPhase I = Fadraciclib administered orally in escalating doses starting at 50mg bid MWF for 3 weeks of a 4 week cycle. Subsequent cohorts will escalate in dose and schedule until optimized phase 2 dose and schedule is achieved. Phase 2 = Recommended Fadraciclib phase 2 dose and schedule administered orally in 28 day cycles.
  • Fadraciclib

Eligibility Criteria

        Inclusion criteria

          1. Age ≥ 18 years

          2. Subjects with histological- or cytological-confirmed, advanced cancer who have
             progressed on (or not been able to tolerate) standard therapy or for whom no standard
             anticancer therapy exists

               1. For Phase 1, all tumor types may be enrolled

               2. For Phase 2, subjects will be enrolled as per the study design section above

          3. ECOG performance status of 0 or 1

          4. Women of childbearing potential (WOCBP) must have a negative pregnancy test (urine or
             serum) within 7 days prior to starting the study drug. Both males and females must
             agree to use effective birth control during the study (prior to the first dose and for
             6 months after the last dose) if conception is possible during this interval.

          5. Subjects must be able to swallow and retain orally administered medication and not
             have any clinically significant GI abnormalities that may alter the absorption, such
             as malabsorption syndrome or major resection of the stomach or bowels.

          6. Able to agree to and sign t he informed consent and to comply with the protocol.

        Exclusion criteria

          1. Subjects with a history of brain metastases or who have signs/symptoms attributable to
             brain metastases and have not been assessed with radiologic imaging to rule out the
             presence of brain metastases. Subjects with treated brain metastases that are
             asymptomatic and have been clinically stable for at least 4 weeks will be eligible.

          2. Subjects who have not received vaccines for SARS-COV-2 within last 3 months and have
             suspected signs and symptoms of COVID-19 or a recent history (within 14 days) of
             contact with any COVID-19 positive subject/isolation/quarantine or subjects with
             confirmed COVID-19.

          3. Subjects with a history of another primary malignancy, other than:

               1. Carcinomas in situ, e.g., breast, cervix, and prostate

               2. Locally excised nonmelanoma skin cancer

               3. No evidence of disease from another primary cancer for 2 or more years and has
                  not taken any anti-cancer treatment in 2 years.

          4. Any other clinically significant acute or chronic medical or psychiatric condition or
             any laboratory abnormality that may increase the risk associated with study drug
             administration or may interfere with the interpretation of study results.

          5. Diseases that significantly affect GI absorption of fadraciclib.

          6. Subjects who have impaired cardiac function or clinically significant cardiac disease.

          7. Presence of active chronic inflammatory bowel disease (ulcerative colitis, Crohn's
             disease) or GI perforation within 6 months of enrollment

          8. Presence of an active infection requiring intravenous antibiotics

          9. Presence of known history of human immunodeficiency virus-1/2 with uncontrolled viral
             load and on medications that may interfere with metabolism

         10. Presence of active hepatitis B virus (HBV) or hepatitis C virus (HCV).

         11. Chemotherapy, biologic therapy, targeted therapy, immunotherapy, extended-field
             radiotherapy, or investigational agents within 5 half-lives or 3 weeks (whichever is
             shorter) prior to administration of first dose of study drug on Day 1 or have not
             recovered from the side effects of such therapy.

         12. Major surgery/surgical therapy for any cause within 4 weeks of the first dose
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose
Time Frame:6 months
Safety Issue:
Description:The incidence rate of dose-limiting toxicities (first cycle only) at each dose level

Secondary Outcome Measures

Measure:Adverse events
Time Frame:24 months
Safety Issue:
Description:Type, frequency, and severity of adverse drug reactions
Measure:AUC
Time Frame:6 months
Safety Issue:
Description:Fadraciclib plasma concentrations
Measure:Cmax
Time Frame:6 months
Safety Issue:
Description:Fadraciclib plasma concentrations
Measure:Tmax
Time Frame:6 months
Safety Issue:
Description:Fadraciclib plasma concentrations
Measure:T1/2
Time Frame:6 months
Safety Issue:
Description:Fadraciclib plasma concentrations

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Cyclacel Pharmaceuticals, Inc.

Trial Keywords

  • Solid tumor
  • lymphoma

Last Updated

July 30, 2021