Advanced Solid TumorsPhase 1NCT03134638
A Study of SY-1365 in Adult Patients With Advanced Solid Tumors
A Phase 1 study testing SY-1365 (Part 1), Carboplatin and Fulvestrant in people with Advanced Solid Tumors and Ovarian Cancer, run by Syros Pharmaceuticals at 20 sites in 3 countries.
Trial summary
This study consists of two parts. Part 1 is a dose-escalation/safety evaluation to provisionally identify a dose and regimen of SY-1365 for further evaluation in Part 2. Following the identification of a recommended dose and regimen from Part 1, the study entered Part 2 to further evaluate safety and the antitumor… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors, Ovarian Cancer, Breast Cancer
- What is being tested?
- SY-1365 (Part 1), Carboplatin and Fulvestrant
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 107 participants
- Where
- 20 sitesin 3 countries
- Study dates
- 12 May 2017to 24 Jun 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years of age or older
- Disease status
- Part 1: any histologically-confirmed metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective
- Part 2, Cohorts 1 and 2, all patients must have a histologically-confirmed diagnosis of high grade serous ovarian cancer (including fallopian tube cancer and/or primary peritoneal cancer)
- Part 2, Cohort 1, patients must have received ≥ 3 prior treatment regimens for ovarian cancer including a platinum-based regimen. Patients whose ovarian cancer harbors a mutation in breast cancer gene (BRCA), either germline or somatic, must have been previously treated with a poly(ADP ribose) polymerase (PARP) inhibitor, or be considered unwilling or ineligible for treatment with a PARP inhibitor
- Part 2, Cohort 2, patients must have received ≥ 1 prior treatment regimen for ovarian cancer, at least 1 of which is a platinum-based regimen
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- Part 2,Cohort 3, all patients must have a histologically-confirmed diagnosis of clear cell ovarian cancer and must have received ≥ 1 prior treatment regimen for clear cell ovarian cancer, at least 1 of which is a platinum-based regimen.
- Part 2, Cohort 4, any histologically-confirmed metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective. Must have accessible tumor tissue and be willing to undergo tumor tissue sampling (biopsies/aspirates) pre-, during, and post-treatment
- Part 2, Cohort 5, postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer who have failed prior treatment with a CDK 4/6 inhibitor in combination with a hormonal therapy (i.e. aromatase inhibitors, fulvestrant). Treatment failure is based on development of clinical or documented progression during treatment with a CDK4/6 inhibitor in combination with hormonal therapy after ≥ 6 months of therapy. Progression following discontinuation of CDK4/6 treatment due to safety and/or tolerability is not considered as treatment failure for purposes of inclusion criteria. Documentation of HR-positive and HER2-negative status must be available.
- At least 1 measurable lesion by RECIST 1.1
- All toxicities (except alopecia) from prior cancer treatments must have resolved to ≤ Grade 1 or returned to baseline levels prior to enrollment
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Life expectancy > 3 months
- Absolute neutrophil count: ≥ 1.5 x 10^9/L
- Platelets: ≥ 100 x 10^9/L
- Hemoglobin: ≥ 9 g/dL
- Total bilirubin ≤ 1.5 x institutional upper limit of normal [ULN]
- AST (SGOT)/ ALT (SGPT): ≤ 3.0 x institutional ULN
- Creatinine ≤ 1.5 x institutional ULN OR creatinine clearance ≥ 60 mL/min by Crockoft-Gault for participants with creatinine levels above institutional normal
- Negative serum pregnancy test for women of child bearing potential
Who cannot join
- Chemotherapy or limited field radiotherapy within 2 weeks, wide field radiotherapy within 4 weeks, or nitrosoureas or mitomycin C within 6 weeks prior to entering the study
- Major surgery within 2 weeks of starting the study treatment, or not recovered to baseline status from the effects of surgery received > 2 weeks prior
- Received any other investigational agents within 4 weeks prior to enrollment, or < 5 half-lives since completion of previous investigational therapy, whichever is shorter
- Received previous non-cytotoxic, FDA-approved anticancer agent within previous 2 weeks, or < 5 half-lives since completion of previous therapy, whichever is shorter
- Prior exposure to transcriptional kinase family CDK inhibitors, such as the CDK7 and CDK9 inhibitors alvocidib (Flavopiridol), dinaciclib, and seliciclib. Exception: previous exposure to cell cycle CDK inhibitors such as CDK4 and CDK6 (eg, palbociclib) is allowed
- Known brain metastases or carcinomatous meningitis. Exception: previously treated brain metastatic disease that remains stable on MRI ≥ 4 weeks prior to enrollment without steroids or anti-epileptic medications
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- History of allergic reactions attributed to compounds of similar chemical composition to SY-1365
- Immunocompromised patients with increased risk of opportunistic infections, including known HIV-positive patients
- Patients with known active Hepatitis B or Hepatitis C infection
- Prior treatment (< 2 weeks before start of SY-1365) with moderate or strong CYP3A4 inducers or strong CYP3A4 inhibitors
- Baseline QT interval corrected with Fridericia's method (QTcF) > 480 ms. NOTE: criterion does not apply to patients with a right or left bundle branch block (QTc interval)
- Significant cardiac risk, including: History of clinically significant cardiac disease or clinically relevant uncontrolled cardiac risk factors
- Uncontrolled intercurrent illness
- Part 2 Only:
- Cohorts 1 and 2: Patients with low-grade ovarian cancer (eg, low grade serous, mucinous carcinoma) are not eligible
- Cohort 2: Prior adverse reaction(s) to carboplatin or any medical condition that precludes re-treatment with carboplatin
- Cohort 5: More than 1 prior line of treatment with systemic chemotherapy for advanced/metastatic disease; Advanced/metastatic disease that is symptomatic and/or with visceral spread that are at risk of life-threatening complications in the short term; Contraindication to receiving fulvestrant OR any medical condition that requires a lower dose of fulvestrant at the initiation of therapy
Trial locations and contacts
20 sites in 3 countries.
20 sites in 3 countries
United States15 sites
Texas Oncology
Austin, Texas, 78705
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
University of Chicago Medical Center
Chicago, Illinois, 60637
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Willamette Valley Cancer Institute and Research Center
Eugene, Oregon, 97401
Texas Oncology
Fort Worth, Texas, 76104
Tennessee Oncology
Nashville, Tennessee, 37203
Columbia University Medical Center
New York, New York, 10032
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Women and Infants Hospital of Rhode Island
Providence, Rhode Island, 02905
South Texas Accelerated Research Therapeutics
San Antonio, Texas, 78229
Palo Alto Medical Foundation Group
San Francisco, California, 94118
Honor Health Research Institute
Scottsdale, Arizona, 85258
France3 sites
Centre Léon Bérard
Lyon, 69373 Lyon Cedex
Institut de Cancérologie de l'Ouest
Saint-Herblain, 44805 Saint Herblain Cedex
Institut Gustave Roussy
Villejuif, 94805 Villejuif Cedex
Canada2 sites
Hamilton Health Sciences
Hamilton, Ontario, L8V 1C3
McGill University Health Center
Montreal, Quebec, H4A 3J1
About this study
Official title: A Phase 1 Study of SY-1365, a Selective CDK7 Inhibitor, in Adult Patients With Advanced Solid Tumors
This study consists of two parts. Part 1 is a dose-escalation/safety evaluation to provisionally identify a dose and regimen of SY-1365 for further evaluation in Part 2.
Following the identification of a recommended dose and regimen from Part 1, the study entered Part 2 to further evaluate safety and the antitumor activity of SY-1365 in patients with select solid tumors, and to confirm target engagement and downstream pathway impact in patients with any solid tumor histology.
Read the detailed description
This study consists of two parts. Part 1 is a dose-escalation/safety evaluation to identify a dose and regimen for further evaluation in Part 2. SY-1365 will be administered intravenously weekly \& twice weekly for 3 weeks of each 4 week cycle. Dose escalation will proceed until the determination of the maximum tolerated dose (MTD) or a recommended dose and regimen for evaluation in Part 2 of the study. Part 1 was concluded in September 2018 with a total of 32 evaluable patients.
Following the identification of a recommended dose and regimen from Part 1, the study entered Part 2 to further evaluate safety and the antitumor activity of SY-1365 in patients with select solid tumors, and to confirm target engagement and downstream pathway impact in patients with any solid tumor histology.
Preliminary anti-tumor activity will be evaluated in up to approximately 102 evaluable patients in Part 2, with SY-1365 administered alone, in combination with carboplatin, or in combination with fulvestrant. Part 2 will consist of five cohorts:
- Cohort 1: approximately 24 patients with advanced ovarian cancer with 3+ previous lines of treatment. Monotherapy
- Cohort 2: approximately 24 patients with relapsed ovarian cancer with previous platinum therapy. SY-1365 + Carboplatin
- Cohort 3: approximately 12 patients with clear cell ovarian cancer. Monotherapy
- Cohort 4: approximately 20-30 patients with biopsy-accessible, advanced solid tumors of any histology. Monotherapy.
- Cohort 5: approximately 12 patients with HR+ metastatic breast cancer post CDK4/6 + hormonal therapy treatment. SY-1365 + fulvestrant.
Overall, the study may enroll up to approximately 137 evaluable patients across dose escalation (Part 1) and expansion cohorts (Part 2, Cohorts 1, 2, 3, 4, and 5).
- Conditions
- Advanced Solid Tumors, Ovarian Cancer, Breast Cancer
- Being tested
- SY-1365 (Part 1), Carboplatin, Fulvestrant, SY-1365 (Cohort 2), SY-1365 (Cohort 5)
- Medical subject headings
- Ovarian Neoplasms, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SY-1365 (Part 1)Drug
Two dosing schedules will be evaluated in dose escalation and a dose(s)/schedule(s) will be determined for Part 2:
- Twice weekly: SY-1365 will be administered by intravenous infusion over 1 or 2 hours twice a week for 3 weeks of each 4 week (28 day) cycle.
- Weekly: SY-1365 will be administered by intravenous infusion over 1 or 2 hours once a week for 3 weeks of each 4 week (28 day) cycle.
CarboplatinDrug
Also called paraplatin
Carboplatin will be administered on Day 1 of each 3 week (21-day) cycle (Part 2 only)
FulvestrantDrug
Also called faslodex
Fulvestrant will be administered as an intramuscular (IM) dose of 500 mg every 2 weeks for the first 3 doses on Day 1 and Day 15 of the first 28-day cycle (Cycle 1), and on Day 1 of the second 28 day cycle (Cycle 2), and monthly thereafter starting on Day 1 of Cycle 3 (Part 2 only)
SY-1365 (Cohort 2)Drug
In combination with carboplatin, SY-1365 will be administered by intravenous infusion over 1 or 2 hours for 2 weeks of each 3 week (21-day) cycle (Part 2 only)
SY-1365 (Cohort 5)Drug
In combination with fulvestrant, SY-1365 will be administered by intravenous infusion over 1 or 2 hours once a week for 3 weeks of each 4 week (28-day) cycle (Part 2 only)
SY-1365 (Part 2 Single Agent)Drug
SY-1365 will be administered by intravenous infusion over 1 or 2 hours twice a week for 3 weeks of each 4 week (28 day) cycle
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation | Experimental | Dose escalation phase to explore maximum tolerated dose across two dosing schedules. SY-1365 will be administered intravenously weekly and twice-weekly for 3 weeks of each 4-week cycle Receives: Drug: SY-1365 (Part 1) |
| Advanced Ovarian Cancer | Experimental | Patients with ovarian cancer previously treated with ≥ 3 prior lines of therapy (SY-1365 single agent) Receives: Drug: SY-1365 (Part 2 Single Agent) |
| Relapsed Ovarian Cancer | Experimental | Patients with ovarian cancer previously treated with ≥ 1 prior line of therapy including a platinum-based regimen (SY-1365 + carboplatin) Receives: Drug: Carboplatin; Drug: SY-1365 (Cohort 2) |
| Clear Cell Ovarian Cancer | Experimental | Patients with clear cell ovarian cancer previously treated with ≥ 1 prior line of therapy (SY-1365 single agent) Receives: Drug: SY-1365 (Part 2 Single Agent) |
| Advanced Solid Tumors | Experimental | Biopsy cohort of approximately 20-30 patients with advanced solid tumors from whom pre- and post-treatment biopsies will be obtained (SY-1365 single agent) Receives: Drug: SY-1365 (Part 2 Single Agent) |
| HR+ breast cancer | Experimental | Patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2) negative advanced or metastatic breast cancer (BC) that has progressed following prior treatment with a cyclin-dependent kinase (CDK)4/6 inhibitor in combination with hormonal therapy (SY-1365 + fulvestrant) Receives: Drug: Fulvestrant; Drug: SY-1365 (Cohort 5) |
What is being measured
The primary outcome is the main question the study is designed to answer.
(Part 1) First-cycle dose-limiting toxicities (DLTs)
Measured: Within 1 year
(Part 1) ECG QTc Interval
Measured: Within 1 year
(Part 1 and 2) Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Measured: Within 1 year
Secondary outcomes (8)
Peak Plasma Concentration (Cmax) of SY-1365 as a single agent (Part 1 and 2) and in combination with carboplatin (Part 2 only)
Measured: Within 1 year
Area under the plasma concentration-time curve from time zero to the last quantifiable time point (AUC0-last) of SY-1365 as a single agent (Part 1 and 2) and in combination with carboplatin (Part 2 only)
Measured: Within 1 year
Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-INF) of SY-1365 as a single agent (Part 1 and 2) and in combination with carboplatin (Part 2 only)
Measured: Within 1 year
(Part 1 and 2) Terminal elimination half life (t1/2)
Measured: Within 1 year
(Part 1 and 2) Evaluate the PD effects of SY-1365 as a single agent (Part 1 and 2) and in combination with carboplatin or fulvestrant (Part 2 only)
Done by measuring the CDK7 occupancy in PBMCs and tumor tissue after single agent or combination administration
Measured: Within 1 year
(Part 2) Evaluation of Objective Response Rate (ORR) in patients with ovarian cancer, breast cancer, and advanced solid tumors as measured by RECIST v1.1
Measured: Within 1 year
(Part 2) Evaluation of Duration of Response (DoR) in patients with ovarian cancer, breast cancer, and advanced solid tumors as measured by RECIST v1.1
Measured: Within 1 year
(Part 2) Evaluation of Disease Control Rate (DCR) in patients with ovarian cancer, breast cancer, and advanced solid tumors as measured by RECIST v1.1
Measured: Within 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2017
- Study start12 May 2017
- Primary completion15 May 2020
- Study completion24 Jun 2020
Why it stopped: Business Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- Syros Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kate Madigan, MD, Study director, Syros Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03134638
- Sponsor's protocol ID
- SY-1365-101
- Status last verified
- Nov 2019
- First submitted
- 19 Apr 2017
- Last updated
- 9 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Sava GP, Fan H, Coombes RC, Buluwela L, Ali S. CDK7 inhibitors as anticancer drugs. Cancer Metastasis Rev. 2020 Sep;39(3):805-823. doi: 10.1007/s10555-020-09885-8.
PubMed 32385714
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of SY-1365, a Selective CDK7 Inhibitor, in Adult Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT03134638
- Acronym / sponsor ID
- SY-1365-101
- Conditions
- Advanced Solid Tumors, Ovarian Cancer, Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business Decision
- Enrolment
- 107 participants (actual)
- Lead sponsor
- Syros PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 12 May 2017 (actual)
- Primary completion
- 15 May 2020 (actual)
- Study completion
- 24 Jun 2020 (actual)
- First posted
- 1 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study consists of two parts. Part 1 is a dose-escalation/safety evaluation to provisionally identify a dose and regimen of SY-1365 for further evaluation in Part 2.
Following the identification of a recommended dose and regimen from Part 1, the study entered Part 2 to further evaluate safety and the antitumor activity of SY-1365 in patients with select solid tumors, and to confirm target engagement and downstream pathway impact in patients with any solid tumor histology.
Detailed description
This study consists of two parts. Part 1 is a dose-escalation/safety evaluation to identify a dose and regimen for further evaluation in Part 2. SY-1365 will be administered intravenously weekly \& twice weekly for 3 weeks of each 4 week cycle. Dose escalation will proceed until the determination of the maximum tolerated dose (MTD) or a recommended dose and regimen for evaluation in Part 2 of the study. Part 1 was concluded in September 2018 with a total of 32 evaluable patients.
Following the identification of a recommended dose and regimen from Part 1, the study entered Part 2 to further evaluate safety and the antitumor activity of SY-1365 in patients with select solid tumors, and to confirm target engagement and downstream pathway impact in patients with any solid tumor histology.
Preliminary anti-tumor activity will be evaluated in up to approximately 102 evaluable patients in Part 2, with SY-1365 administered alone, in combination with carboplatin, or in combination with fulvestrant. Part 2 will consist of five cohorts:
- Cohort 1: approximately 24 patients with advanced ovarian cancer with 3+ previous lines of treatment. Monotherapy
- Cohort 2: approximately 24 patients with relapsed ovarian cancer with previous platinum therapy. SY-1365 + Carboplatin
- Cohort 3: approximately 12 patients with clear cell ovarian cancer. Monotherapy
- Cohort 4: approximately 20-30 patients with biopsy-accessible, advanced solid tumors of any histology. Monotherapy.
- Cohort 5: approximately 12 patients with HR+ metastatic breast cancer post CDK4/6 + hormonal therapy treatment. SY-1365 + fulvestrant.
Overall, the study may enroll up to approximately 137 evaluable patients across dose escalation (Part 1) and expansion cohorts (Part 2, Cohorts 1, 2, 3, 4, and 5).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation | Experimental | Drug: SY-1365 (Part 1)Dose escalation phase to explore maximum tolerated dose across two dosing schedules. SY-1365 will be administered intravenously weekly and twice-weekly for 3 weeks of each 4-week cycle |
| Advanced Ovarian Cancer | Experimental | Drug: SY-1365 (Part 2 Single Agent)Patients with ovarian cancer previously treated with ≥ 3 prior lines of therapy (SY-1365 single agent) |
| Relapsed Ovarian Cancer | Experimental | Drug: Carboplatin, Drug: SY-1365 (Cohort 2)Patients with ovarian cancer previously treated with ≥ 1 prior line of therapy including a platinum-based regimen (SY-1365 + carboplatin) |
| Clear Cell Ovarian Cancer | Experimental | Drug: SY-1365 (Part 2 Single Agent)Patients with clear cell ovarian cancer previously treated with ≥ 1 prior line of therapy (SY-1365 single agent) |
| Advanced Solid Tumors | Experimental | Drug: SY-1365 (Part 2 Single Agent)Biopsy cohort of approximately 20-30 patients with advanced solid tumors from whom pre- and post-treatment biopsies will be obtained (SY-1365 single agent) |
| HR+ breast cancer | Experimental | Drug: Fulvestrant, Drug: SY-1365 (Cohort 5)Patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2) negative advanced or metastatic breast cancer (BC) that has progressed following prior treatment with a cyclin-dependent kinase (CDK)4/6 inhibitor in combination with hormonal therapy (SY-1365 + fulvestrant) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 18 years of age or older
- Disease status
- At least 1 measurable lesion by RECIST 1.1
- All toxicities (except alopecia) from prior cancer treatments must have resolved to ≤ Grade 1 or returned to baseline levels prior to enrollment
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Key exclusion criteria (17 listed)
- Chemotherapy or limited field radiotherapy within 2 weeks, wide field radiotherapy within 4 weeks, or nitrosoureas or mitomycin C within 6 weeks prior to entering the study
- Major surgery within 2 weeks of starting the study treatment, or not recovered to baseline status from the effects of surgery received > 2 weeks prior
- Received any other investigational agents within 4 weeks prior to enrollment, or < 5 half-lives since completion of previous investigational therapy, whichever is shorter
- Received previous non-cytotoxic, FDA-approved anticancer agent within previous 2 weeks, or < 5 half-lives since completion of previous therapy, whichever is shorter
- Prior exposure to transcriptional kinase family CDK inhibitors, such as the CDK7 and CDK9 inhibitors alvocidib (Flavopiridol), dinaciclib, and seliciclib. Exception: previous exposure to cell cycle CDK inhibitors such as CDK4 and CDK6 (eg, palbociclib) is allowed
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SY-1365 (Part 1)Two dosing schedules will be evaluated in dose escalation and a dose(s)/schedule(s) will be determined for Part 2: * Twice weekly: SY-1365 will be administered by intravenous infusion over 1 or 2 hours twice a week for 3 weeks of each 4 week (28 day) cycle. * Weekly: SY-1365 will be administered by intravenous infusion over 1 or 2 hours once a week for 3 weeks of each 4 week (28 day) cycle. | Drug | Dose Escalation |
| CarboplatinAlso: paraplatinCarboplatin will be administered on Day 1 of each 3 week (21-day) cycle (Part 2 only) | Drug | Relapsed Ovarian Cancer |
| FulvestrantAlso: faslodexFulvestrant will be administered as an intramuscular (IM) dose of 500 mg every 2 weeks for the first 3 doses on Day 1 and Day 15 of the first 28-day cycle (Cycle 1), and on Day 1 of the second 28 day cycle (Cycle 2), and monthly thereafter starting on Day 1 of Cycle 3 (Part 2 only) | Drug | HR+ breast cancer |
| SY-1365 (Cohort 2)In combination with carboplatin, SY-1365 will be administered by intravenous infusion over 1 or 2 hours for 2 weeks of each 3 week (21-day) cycle (Part 2 only) | Drug | Relapsed Ovarian Cancer |
| SY-1365 (Cohort 5)In combination with fulvestrant, SY-1365 will be administered by intravenous infusion over 1 or 2 hours once a week for 3 weeks of each 4 week (28-day) cycle (Part 2 only) | Drug | HR+ breast cancer |
| SY-1365 (Part 2 Single Agent)SY-1365 will be administered by intravenous infusion over 1 or 2 hours twice a week for 3 weeks of each 4 week (28 day) cycle | Drug | Advanced Ovarian Cancer, Advanced Solid Tumors, Clear Cell Ovarian Cancer |
Primary outcome
(Part 1) First-cycle dose-limiting toxicities (DLTs)
Time frame: Within 1 year
(Part 1) ECG QTc Interval
Time frame: Within 1 year
(Part 1 and 2) Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: Within 1 year
8 secondary outcomes
Peak Plasma Concentration (Cmax) of SY-1365 as a single agent (Part 1 and 2) and in combination with carboplatin (Part 2 only)
Time frame: Within 1 year
Area under the plasma concentration-time curve from time zero to the last quantifiable time point (AUC0-last) of SY-1365 as a single agent (Part 1 and 2) and in combination with carboplatin (Part 2 only)
Time frame: Within 1 year
Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-INF) of SY-1365 as a single agent (Part 1 and 2) and in combination with carboplatin (Part 2 only)
Time frame: Within 1 year
(Part 1 and 2) Terminal elimination half life (t1/2)
Time frame: Within 1 year
(Part 1 and 2) Evaluate the PD effects of SY-1365 as a single agent (Part 1 and 2) and in combination with carboplatin or fulvestrant (Part 2 only)
Time frame: Within 1 year
(Part 2) Evaluation of Objective Response Rate (ORR) in patients with ovarian cancer, breast cancer, and advanced solid tumors as measured by RECIST v1.1
Time frame: Within 1 year
(Part 2) Evaluation of Duration of Response (DoR) in patients with ovarian cancer, breast cancer, and advanced solid tumors as measured by RECIST v1.1
Time frame: Within 1 year
(Part 2) Evaluation of Disease Control Rate (DCR) in patients with ovarian cancer, breast cancer, and advanced solid tumors as measured by RECIST v1.1
Time frame: Within 1 year
Results and safety
The study was stopped early (reason given: Business Decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2021.
- Derived from this study: PubMed 32385714Sava GP, Fan H, Coombes RC, Buluwela L, Ali S. CDK7 inhibitors as anticancer drugs. Cancer Metastasis Rev. 2020 Sep;39(3):805-823. doi: 10.1007/s10555-020-09885-8.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kate Madigan, MD study director
Syros Pharmaceuticals
20 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SY-1365 (Part 1), Carboplatin and Fulvestrant in people with Advanced Solid Tumors and Ovarian Cancer, run by Syros Pharmaceuticals at 20 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, France, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Business Decision). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
(Part 1) First-cycle dose-limiting toxicities (DLTs) (time frame: Within 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03134638, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2021.