Solid TumorsPhase 1NCT02537561
Talazoparib in Combination With Gemcitabine and Cisplatin in Patients With Advanced Solid Tumors
A Phase 1 study testing Cisplatin, Gemcitabine and Talazoparib in people with Solid Tumors and Carcinoma, Non-Small Cell Lung, run by Washington University School of Medicine.
Trial summary
In this proposed study the investigators will combine gemcitabine and cisplatin with talazoparib to determine the recommended Phase 2 dose (RP2D) of this combination regimen. After determination of the RP2D patients with lung cancer whose tumors carry molecular alterations in DNA repair pathway genes will be enrolled… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors, Carcinoma, Non-Small Cell Lung, Non-Small Cell Lung Cancer
- What is being tested?
- Cisplatin, Gemcitabine and Talazoparib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Dec 2015to Dec 2018
- 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
- Histologically confirmed diagnosis of advanced solid tumor for which no curative standard treatment options exist and for which gemcitabine and cisplatin is a suitable treatment regimen.
- After the determination of the maximum tolerated dose, an expansion cohort of 20 patients with non-small cell lung cancer whose tumors demonstrate variants in DNA repair pathway genes will be enrolled.
- Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
- Prior treatment for this disease is allowed if it has been completed at least 2 weeks prior to study enrollment and if all treatment-related toxicities are resolved. Prior exposure to a PARP inhibitor is allowed for patients in the dose-finding portion of the study.
- At least 18 years of age.
- ECOG performance status ≤ 1
Show all 17Show fewer
- Normal bone marrow and organ function as defined below:
- Leukocytes ≥ 3,000/mcL
- Absolute neutrophil count ≥ 1,500/mcl
- Platelets ≥ 100,000/mcl
- Total bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Tissue available for sequencing (either archival tissue or readily accessible tumor for fresh routine biopsy).
- Able to swallow tablets.
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Who cannot join
- A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
- Received any other investigational agent within 2 weeks of starting the first dose on study.
- Symptomatic brain metastases. Known brain metastases are allowed if asymptomatic and previously treated. Patients must be at least 4 weeks post-brain radiation therapy.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin, gemcitabine, talazoparib, or other agents used in the study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active coronary artery disease, uncontrolled seizure, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
- Known HIV-positivity.
About this study
Official title: A Phase I Adaptive Design Trial of Talazoparib in Combination With Gemcitabine and Cisplatin in Patients With Advanced Solid Tumors
In this proposed study the investigators will combine gemcitabine and cisplatin with talazoparib to determine the recommended Phase 2 dose (RP2D) of this combination regimen. After determination of the RP2D patients with lung cancer whose tumors carry molecular alterations in DNA repair pathway genes will be enrolled to an expansion cohort to determine anti-tumor efficacy. Tissue samples of patients with confirmed partial response, complete response, and non-responders will be obtained for whole exome, and transcriptome sequencing to characterize the genetic alterations associated with response to therapy.
- Conditions
- Solid Tumors, Carcinoma, Non-Small Cell Lung, Non-Small Cell Lung Cancer, Non-Small-Cell Lung Carcinoma, Nonsmall Cell Lung Cancer
- Being tested
- Cisplatin, Gemcitabine, Talazoparib
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CisplatinDrug
Also called cis-DDP, cis-Platinum II, cis-Diamminedichloroplatinum, DDP
GemcitabineDrug
Also called Gemzar®
TalazoparibDrug
Also called BMN 673
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Cisplatin, Gemcitabine, Talazoparib Solid Tumors | Experimental | * Dose levels of the drugs will be dependent on which dose level the participants is enrolled.
* Cisplatin will be infused as a 30 minute intravenous piggyback (IVPB) on Day 1 of each 21 day cycle.
* Gemcitabine will be infused as a 30 minute IVPB on Days 1 and 8 of each 21 day cycle. On day 1, gemcitabine will be given before cisplatin.
* Talazoparib will be started with cycle 2. It is an oral drug which will be administered on an outpatient basis daily.
* Cisplatin and gemcitabine will be given for a total of 6 cycles.
* Talazoparib may be continued as a single agent maintenance therapy. Receives: Drug: Cisplatin; Drug: Gemcitabine; Drug: Talazoparib |
| Arm 2: Cisplatin, Gemcitabine, Talazoparib NSCLC | Experimental | * Dose levels of the drugs will depend on what the MTD is in the dose escalation portion of the study
* Cisplatin will be infused as a 30 minute intravenous piggyback (IVPB) on Day 1 of each 21 day cycle.
* Gemcitabine will be infused as a 30 minute IVPB on Days 1 and 8 of each 21 day cycle. On day 1, gemcitabine will be given before cisplatin.
* Talazoparib will be started with cycle 2. It is an oral drug which will be administered on an outpatient basis daily.
* Cisplatin and gemcitabine will be given for a total of 6 cycles.
* Talazoparib may be continued as a single agent maintenance therapy. Receives: Drug: Cisplatin; Drug: Gemcitabine; Drug: Talazoparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and toxicities as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Measured: 30 days after completion of treatment (estimated average to be 7 months)
Maximum tolerated dose (MTD)
The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 30% of patients in a cohort are expected to experience a dose-limiting toxicity (DLT) during the second cycle based on the CRM algorithm. Dose escalations will proceed until the MTD is determined.
Measured: Completion of dose escalation portion of study (approximately 12 months)
Objective response rate (ORR) in preselected patients with BRCAness tumoral genotype
ORR - proportion of patients who achieved a complete response or a partial response
Measured: Up to completion of treatment (estimated average of 6 months)
Secondary outcomes (4)
Disease control rate (DCR)
- DCR - percentage of participants who have achieved complete response, partial response, and stable disease
- Complete response: disappearance of all lesions and normalization of tumor marker level
- Partial response: at least a 30% decrease in the sum of the diameters of target lesions and no new lesions
- Stable disease: neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease
Measured: Until death (estimated average to be 12 months)
Progression-free survival (PFS)
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
-Progressive disease - At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, appearance of one more new lesions PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Measured: Until death (estimated average to be 12 months)
Objective response rate (ORR)
ORR - proportion of patients who achieved a complete response or a partial response
Measured: Up to completion of treatment (estimated average of 6 months)
Overall survival (OS)
OS: duration of time from start of treatment to time of death from any cause
Measured: Until death (estimated average to be 12 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2015 (estimated)
- Study startDec 2015
- Primary completionJun 2018 (estimated)
- Study completionDec 2018 (estimated)
Why it stopped: The pharmaceutical company did not want to follow through with support for the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- BioMarin Pharmaceutical
- Responsible party
- Sponsor
- Investigators
- Saiama Waqar, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02537561
- Sponsor's protocol ID
- 15-x279
- Status last verified
- Feb 2016
- First submitted
- 28 Aug 2015
- Last updated
- 11 Feb 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Adaptive Design Trial of Talazoparib in Combination With Gemcitabine and Cisplatin in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT02537561
- Acronym / sponsor ID
- 15-x279
- Conditions
- Solid Tumors, Carcinoma, Non-Small Cell Lung, Non-Small Cell Lung Cancer, Non-Small-Cell Lung Carcinoma, Nonsmall Cell Lung Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The pharmaceutical company did not want to follow through with support for the study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- BioMarin Pharmaceutical
- Study start
- Dec 2015
- Primary completion
- Jun 2018 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 1 Sep 2015 (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.
In this proposed study the investigators will combine gemcitabine and cisplatin with talazoparib to determine the recommended Phase 2 dose (RP2D) of this combination regimen. After determination of the RP2D patients with lung cancer whose tumors carry molecular alterations in DNA repair pathway genes will be enrolled to an expansion cohort to determine anti-tumor efficacy. Tissue samples of patients with confirmed partial response, complete response, and non-responders will be obtained for whole exome, and transcriptome sequencing to characterize the genetic alterations associated with response to therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Cisplatin, Gemcitabine, Talazoparib Solid Tumors | Experimental | Drug: Cisplatin, Drug: Gemcitabine, Drug: Talazoparib* Dose levels of the drugs will be dependent on which dose level the participants is enrolled. * Cisplatin will be infused as a 30 minute intravenous piggyback (IVPB) on Day 1 of each 21 day cycle. * Gemcitabine will be infused as a 30 minute IVPB on Days 1 and 8 of each 21 day cycle. On day 1, gemcitabine will be given before cisplatin. * Talazoparib will be started with cycle 2. It is an oral drug which will be administered on an outpatient basis daily. * Cisplatin and gemcitabine will be given for a total of 6 cycles. * Talazoparib may be continued as a single agent maintenance therapy. |
| Arm 2: Cisplatin, Gemcitabine, Talazoparib NSCLC | Experimental | Drug: Cisplatin, Drug: Gemcitabine, Drug: Talazoparib* Dose levels of the drugs will depend on what the MTD is in the dose escalation portion of the study * Cisplatin will be infused as a 30 minute intravenous piggyback (IVPB) on Day 1 of each 21 day cycle. * Gemcitabine will be infused as a 30 minute IVPB on Days 1 and 8 of each 21 day cycle. On day 1, gemcitabine will be given before cisplatin. * Talazoparib will be started with cycle 2. It is an oral drug which will be administered on an outpatient basis daily. * Cisplatin and gemcitabine will be given for a total of 6 cycles. * Talazoparib may be continued as a single agent maintenance therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Histologically confirmed diagnosis of advanced solid tumor for which no curative standard treatment options exist and for which gemcitabine and cisplatin is a suitable treatment regimen.
- After the determination of the maximum tolerated dose, an expansion cohort of 20 patients with non-small cell lung cancer whose tumors demonstrate variants in DNA repair pathway genes will be enrolled.
- Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
- Prior treatment for this disease is allowed if it has been completed at least 2 weeks prior to study enrollment and if all treatment-related toxicities are resolved. Prior exposure to a PARP inhibitor is allowed for patients in the dose-finding portion of the study.
- At least 18 years of age.
Key exclusion criteria (7 listed)
- A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
- Received any other investigational agent within 2 weeks of starting the first dose on study.
- Symptomatic brain metastases. Known brain metastases are allowed if asymptomatic and previously treated. Patients must be at least 4 weeks post-brain radiation therapy.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin, gemcitabine, talazoparib, or other agents used in the study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active coronary artery disease, uncontrolled seizure, or psychiatric illness/social situations that would limit compliance with study requirements.
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 |
|---|---|---|
| CisplatinAlso: cis-DDP, cis-Platinum II, cis-Diamminedichloroplatinum, DDP | Drug | Arm 1: Cisplatin, Gemcitabine, Talazoparib Solid Tumors, Arm 2: Cisplatin, Gemcitabine, Talazoparib NSCLC |
| GemcitabineAlso: Gemzar® | Drug | Arm 1: Cisplatin, Gemcitabine, Talazoparib Solid Tumors, Arm 2: Cisplatin, Gemcitabine, Talazoparib NSCLC |
| TalazoparibAlso: BMN 673 | Drug | Arm 1: Cisplatin, Gemcitabine, Talazoparib Solid Tumors, Arm 2: Cisplatin, Gemcitabine, Talazoparib NSCLC |
Primary outcome
Safety and toxicities as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Time frame: 30 days after completion of treatment (estimated average to be 7 months)
Maximum tolerated dose (MTD)
Time frame: Completion of dose escalation portion of study (approximately 12 months)
The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 30% of patients in a cohort are expected to experience a dose-limiting toxicity (DLT) during the second cycle based on the CRM algorithm. Dose escalations will proceed until the MTD is determined.
Objective response rate (ORR) in preselected patients with BRCAness tumoral genotype
Time frame: Up to completion of treatment (estimated average of 6 months)
ORR - proportion of patients who achieved a complete response or a partial response
4 secondary outcomes
Disease control rate (DCR)
Time frame: Until death (estimated average to be 12 months)
Progression-free survival (PFS)
Time frame: Until death (estimated average to be 12 months)
Objective response rate (ORR)
Time frame: Up to completion of treatment (estimated average of 6 months)
Overall survival (OS)
Time frame: Until death (estimated average to be 12 months)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2016.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
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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.
Saiama Waqar, M.D. principal investigator
Washington University School of Medicine
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cisplatin, Gemcitabine and Talazoparib in people with Solid Tumors and Carcinoma, Non-Small Cell Lung, run by Washington University School of Medicine.
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 17 inclusion and 7 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: withdrawn, as of the sponsor's last update on 11 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
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 withdrawn before enrolling participants, so there are no results.
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?
Safety and toxicities as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (time frame: 30 days after completion of treatment (estimated average to be 7 months)). 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?
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 11 Feb 2016.