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.
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
Drug | Synonyms | Arms |
---|
Fadraciclib | CYC065 | Phase 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
Name | Type | Description | Interventions |
---|
Phase I Dose escalation | Experimental | Phase 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. | |
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
Last Updated
July 30, 2021