Advanced or Metastatic Breast CancerPhase 1NCT01676753
Phase 1b Trial of Dinaciclib With Pembrolizumab for Advanced Breast Cancer
A Phase 1 study testing Dinaciclib and Pembrolizumab in people with Advanced or Metastatic Breast Cancer and Triple Negative Breast Cancer, run by Jo Chien at 1 site in United States.
Trial summary
The purpose of this trial is to determine the safety and tolerability (maximum tolerated dose (MTD)) of weekly dinaciclib in combination with pembrolizumab in patients with advanced breast cancer. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Advanced or Metastatic Breast Cancer, Triple Negative Breast Cancer
- What is being tested?
- Dinaciclib and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Dec 2016to 28 Feb 2022
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically documented, incurable, unresectable locally advanced, or metastatic breast cancer
- Histologically documented metastatic or locally advanced unresectable breast cancer that is ER and progesterone receptor (PR) <10% expression and does not over-express Hormone Estrogen Receptor-Positive (HER2) protein (Immunohistochemistry (IHC) 0, 1+, or 2+ and Fluorescent in situ hybridization (FISH) <2.0)
- Patient must consent to a biopsy of a site of disease unless the only site of disease is lung/pleura, bone, or deemed unsafe by the principal investigator
- Patient is male or female and ≥18 years of age on the day of signing informed consent.
- Patient must have performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale and life expectancy > 3 months
- Patient must have evaluable disease
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- Patient must have adequate organ function as indicated by the following laboratory values:
- Hematological
- Absolute neutrophil count (ANC) ≥ 1,500 /μL
- Platelets ≥ 100,000 /μL
- Hemoglobin ≥ 9 g/dL
- Renal
- Serum creatinine or calculated creatinine clearance ≤ 1.5 x upper limit of normal (ULN) OR
- ≥ 60 mL/min for patients with creatinine levels > 1.5 x institutional ULN
- Hepatic
- Serum total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 x ULN
- Aspartate aminotransferase (AST) / serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) / serum glutamic-pyruvic transaminase (SGPT) ≤ 2.5 x ULN, ≤ 5 x ULN if liver metastasis
- Coagulation
- Prothrombin time (PT)/International Normalized Ratio (INR) ≤ 1.2 x ULN
- Partial thromboplastin time (PTT) ≤ 1.2 x ULN
- Female patient of childbearing potential must have a negative serum or urine pregnancy test β-human chorionic gonadotropin (hCG) within 72 hours prior to first doses of study medication . If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication.
- Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- Patient has voluntarily agreed to participate by giving written informed consent
- Concomitant use of bisphosphonates or nuclear factor-κB (RANK) ligand inhibitors is allowed.
- Both men and women and members of all races and ethnic groups are eligible for this trial.
Who cannot join
- Patient who has had radiotherapy within 1 week (or unresolved radiation-related toxicities), chemotherapy within 2 weeks or 5 half-lives, whichever is longer (6 weeks for nitrosoureas, mitomycin C or bevacizumab), anti-cancer monoclonal antibody for direct anti-neoplastic treatment within 3 weeks, or who has not recovered from toxicity due to previous agents administered. If the patient has residual toxicity from prior treatment, toxicity must be ≤ Grade 1 (except for neuropathy and alopecia).
- > 2 lines of prior chemotherapy in the metastatic setting
- Serum lactate dehydrogenase (LDH) > 1.5x institutional ULN
- Patients less than 2 weeks post major surgical procedure (all surgical wounds must be fully healed). For the purpose of this criterion, a major surgical procedure is defined as one requiring the administration of general anesthesia.
- Patient is currently participating in a study with an investigational compound or device.
- Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. However, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 4 weeks prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis on brain imaging within 4 weeks of enrollment (2) off steroids for 2 weeks. Patients with clinically insignificant brain metastases that do not require treatment are eligible.
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- Patient has a primary central nervous system tumor
- Patient has known hypersensitivity to the components of study drug or its analogs.
- Patient has a history or current evidence of clinically significant heart disease including:
- Clinically significant congestive heart failure, unstable angina pectoris,
- Clinically significant cardiac arrhythmia,
- Myocardial infarction during the last 6 months, and/or a current ECG tracing that is abnormal in the opinion of the treating Investigator,
- QTc prolongation >480 msec (Bazett's Formula),
- Congenitally long QT syndrome, and/or current anti-arrhythmic therapy
- Patient with evidence of clinically significant bradycardia (HR <50), or a history of clinically significant bradyarrhythmias such as sick sinus syndrome, 2nd degree atrioventricular (AV) block (Mobitz Type 2), Patient with uncontrolled hypertension (≥140/90 mmHg). Patients who are controlled on antihypertensive medication will be allowed to enter the study.
- Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
- Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Patient is, at the time of signing informed consent, a regular user of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse.
- Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study
- Patient is known to be Human Immunodeficiency Virus (HIV)-positive
- Patient has known history of active Hepatitis A, B, or C
- Patients who have known allergic reactions to IV contrast dye despite standard prophylaxis
- Patients who require medications that are strong CYP3A4 inhibitors or inducers.
- Patients who have discontinued any of these medications must have a wash-out period of at least 5 days or at least 5 half-lives of the drug (whichever is longer) prior to the first dose of dinaciclib (Refer to Appendix 2 Drugs that interact strongly with CYP3A4).
- Patients requiring warfarin therapy are excluded, low molecular weight heparin is permitted.
- Patient has a diagnosis of immunodeficiency or is receiving ongoing immunosuppressive therapy, including systemic or enteric corticosteroids except for non-systemically absorbed treatments (such as inhaled or topical steroid therapy for asthma, chronic obstructive pulmonary disease, allergic rhinitis). Patient must be off systemic steroid or any other form of immunosuppressive therapy within 7 days prior to first dose of trial treatment.
- Patient is diagnosed with active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Note: replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
- Patient has history of interstitial lung disease or known history of, or any evidence of active, noninfectious pneumonitis.
- Patient has history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or prior allogeneic bone marrow transplantation or prior solid organ transplantation.
- Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this study
Official title: A Phase 1b Trial of the Cyclin-dependent Kinase Inhibitor Dinaciclib in Combination With Pembrolizumab in Patients With Advanced Breast Cancer and Assessment of MYC Oncogene Overexpression
The purpose of this trial is to determine the safety and tolerability (maximum tolerated dose (MTD)) of weekly dinaciclib in combination with pembrolizumab in patients with advanced breast cancer. Once this is defined, dose expansion will be performed at this MTD in patients with metastatic or locally advanced and unresectable triple negative breast cancer, to evaluate the efficacy of combined dinaciclib and pembrolizumab.
Read the detailed description
PRIMARY OBJECTIVE:
- Define the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of dinaciclib
SECONDARY OBJECTIVE:
- Evaluation of the preliminary efficacy of this combination using RECIST 1.1 and irRECIST.
EXPLORATORY OBJECTIVE:
- Characterizing and correlating PDL-1 and MYC overexpression with clinical response.
OUTLINE:
This is an open-label phase Ib trial of weekly dinaciclib in combination pembrolizumab in participants with advanced triple negative breast cancer. Participants will undergo a single needle biopsy of a site of active disease prior to initiating treatment of Pembrolizumab and dinaciclib in 21 day cycles. The dose of dinaciclib will be escalated following a toxicity probability interval (TPI) design where dose-limiting toxicities (DLT) observed during the first cycle will be used to determine whether additional participants should be enrolled at the same, higher, or lower dose level. Treatment will continue until disease progression, intolerable toxicity, or participant withdraws consent. In the event of a complete response (CR), participants may elect to hold dinaciclib treatment and continue with pembrolizumab alone. At the time of radiographic disease progression, dinaciclib can be resumed at the same dose as at the time of discontinuation. Participants will be followed for 30 days after the last dose of treatment.
- Being tested
- Dinaciclib, Pembrolizumab
- Medical subject headings
- Breast Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DinaciclibDrug
Also called SCH727965
Given IV
PembrolizumabDrug
Also called Keytruda
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (Dinaciclib, Pembrolizumab) | Experimental | Pembrolizumab will be administered on Day 1, every 3 weeks at a fixed dose of 200 mg IV. Dinaciclib will be administered D1 and D8 of a 21 day cycle by 2-hour intravenous infusion starting at Dose Level (DL) 1 of 12 mg/m^2. Further dose escalation cohorts are defined as follows: DL 2: 18 mg/m^2, DL 3: 25 mg/m^2, DL 4: 33 mg/m^2, and DL 5: 50 mg/m^2 Receives: Drug: Dinaciclib; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD)
The MTD is determined by the number of dose-limiting toxicities reported by participants in the first cycle of treatment.
Measured: Up to 1 cycle (1 cycle is equal to 21 days)
Proportion of participants with reported dose-limiting toxicities (DLTs)
Dose-limiting hematologic and non-hematologic toxicities classified using the CTCAE, will be based on events occurring during the first cycle of study drug administration. To be considered a dose-limiting toxicity, an adverse experience must be related to one or both of the study drugs, and must not be related to disease progression or intercurrent illnesses. Participants must receive Day 1 and Day 8 treatments of dinaciclib during the first cycle in order to be evaluable for DLTs (unless missed doses are due to toxicity).
Measured: Up to 1 cycle (1 cycle is equal to 21 days)
Secondary outcomes (1)
Overall Response Rate
Overall tumor response and time to progression will be assessed using RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 criteria and immune-related RECIST (irRECIST) which takes into account the clinical condition/stability of subjects in addition to tumor imaging. The rate of participants with a confirmed response classified as Complete Response (CR, iCR) (the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm) or a Partial Response (PR, iPR) (defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters or unconfirmed progressive disease (iUPD) will be reported.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2012 (estimated)
- Study start28 Dec 2016
- Primary completion30 Jun 2020
- Study completion28 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced or Metastatic Breast CancerStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jo Chien
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor-investigator, Jo Chien, University of California, San Francisco
- Investigators
- A. Jo Chien, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01676753
- Sponsor's protocol ID
- 16758
- Other IDs
- NCI-2018-01053
- Status last verified
- Sep 2022
- First submitted
- 24 Aug 2012
- Last updated
- 21 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Trial of the Cyclin-dependent Kinase Inhibitor Dinaciclib in Combination With Pembrolizumab in Patients With Advanced Breast Cancer and Assessment of MYC Oncogene Overexpression
- ClinicalTrials.gov ID
- NCT01676753
- Acronym / sponsor ID
- 16758
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Jo ChienUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 28 Dec 2016 (actual)
- Primary completion
- 30 Jun 2020 (actual)
- Study completion
- 28 Feb 2022 (actual)
- First posted
- 31 Aug 2012 (estimated)
- 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.
The purpose of this trial is to determine the safety and tolerability (maximum tolerated dose (MTD)) of weekly dinaciclib in combination with pembrolizumab in patients with advanced breast cancer. Once this is defined, dose expansion will be performed at this MTD in patients with metastatic or locally advanced and unresectable triple negative breast cancer, to evaluate the efficacy of combined dinaciclib and pembrolizumab.
Detailed description
PRIMARY OBJECTIVE:
- Define the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of dinaciclib
SECONDARY OBJECTIVE:
- Evaluation of the preliminary efficacy of this combination using RECIST 1.1 and irRECIST.
EXPLORATORY OBJECTIVE:
- Characterizing and correlating PDL-1 and MYC overexpression with clinical response.
OUTLINE:
This is an open-label phase Ib trial of weekly dinaciclib in combination pembrolizumab in participants with advanced triple negative breast cancer. Participants will undergo a single needle biopsy of a site of active disease prior to initiating treatment of Pembrolizumab and dinaciclib in 21 day cycles. The dose of dinaciclib will be escalated following a toxicity probability interval (TPI) design where dose-limiting toxicities (DLT) observed during the first cycle will be used to determine whether additional participants should be enrolled at the same, higher, or lower dose level. Treatment will continue until disease progression, intolerable toxicity, or participant withdraws consent. In the event of a complete response (CR), participants may elect to hold dinaciclib treatment and continue with pembrolizumab alone. At the time of radiographic disease progression, dinaciclib can be resumed at the same dose as at the time of discontinuation. Participants will be followed for 30 days after the last dose of treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (Dinaciclib, Pembrolizumab) | Experimental | Drug: Dinaciclib, Drug: PembrolizumabPembrolizumab will be administered on Day 1, every 3 weeks at a fixed dose of 200 mg IV. Dinaciclib will be administered D1 and D8 of a 21 day cycle by 2-hour intravenous infusion starting at Dose Level (DL) 1 of 12 mg/m^2. Further dose escalation cohorts are defined as follows: DL 2: 18 mg/m^2, DL 3: 25 mg/m^2, DL 4: 33 mg/m^2, and DL 5: 50 mg/m^2 |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Histologically or cytologically documented, incurable, unresectable locally advanced, or metastatic breast cancer
- Histologically documented metastatic or locally advanced unresectable breast cancer that is ER and progesterone receptor (PR) <10% expression and does not over-express Hormone Estrogen Receptor-Positive (HER2) protein (Immunohistochemistry (IHC) 0, 1+, or 2+ and Fluorescent in situ hybridization (FISH) <2.0)
- Patient must consent to a biopsy of a site of disease unless the only site of disease is lung/pleura, bone, or deemed unsafe by the principal investigator
- Patient is male or female and ≥18 years of age on the day of signing informed consent.
- Patient must have performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale and life expectancy > 3 months
Key exclusion criteria (30 listed)
- Patient who has had radiotherapy within 1 week (or unresolved radiation-related toxicities), chemotherapy within 2 weeks or 5 half-lives, whichever is longer (6 weeks for nitrosoureas, mitomycin C or bevacizumab), anti-cancer monoclonal antibody for direct anti-neoplastic treatment within 3 weeks, or who has not recovered from toxicity due to previous agents administered. If the patient has residual toxicity from prior treatment, toxicity must be ≤ Grade 1 (except for neuropathy and alopecia).
- > 2 lines of prior chemotherapy in the metastatic setting
- Serum lactate dehydrogenase (LDH) > 1.5x institutional ULN
- Patients less than 2 weeks post major surgical procedure (all surgical wounds must be fully healed). For the purpose of this criterion, a major surgical procedure is defined as one requiring the administration of general anesthesia.
- Patient is currently participating in a study with an investigational compound or device.
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 |
|---|---|---|
| DinaciclibAlso: SCH727965Given IV | Drug | Treatment (Dinaciclib, Pembrolizumab) |
| PembrolizumabAlso: KeytrudaGiven IV | Drug | Treatment (Dinaciclib, Pembrolizumab) |
Primary outcome
Maximum tolerated dose (MTD)
Time frame: Up to 1 cycle (1 cycle is equal to 21 days)
The MTD is determined by the number of dose-limiting toxicities reported by participants in the first cycle of treatment.
Proportion of participants with reported dose-limiting toxicities (DLTs)
Time frame: Up to 1 cycle (1 cycle is equal to 21 days)
Dose-limiting hematologic and non-hematologic toxicities classified using the CTCAE, will be based on events occurring during the first cycle of study drug administration. To be considered a dose-limiting toxicity, an adverse experience must be related to one or both of the study drugs, and must not be related to disease progression or intercurrent illnesses. Participants must receive Day 1 and Day 8 treatments of dinaciclib during the first cycle in order to be evaluable for DLTs (unless missed doses are due to toxicity).
1 secondary outcome
Overall Response Rate
Time frame: Up to 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2022.
- Individual participant dataSharing planned: No
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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.
A. Jo Chien, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dinaciclib and Pembrolizumab in people with Advanced or Metastatic Breast Cancer and Triple Negative Breast Cancer, run by Jo Chien at 1 site in United States.
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 27 inclusion and 30 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: finished, as of the sponsor's last update on 21 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum tolerated dose (MTD) (time frame: Up to 1 cycle (1 cycle is equal to 21 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Sep 2022.