Solid TumorsPhase 1NCT00749502
A Study of MK4827 in Participants With Advanced Solid Tumors or Hematologic Malignancies (MK-4827-001 AM8)
A Phase 1 study testing MK-4827 in people with Solid Tumors and Chronic Lymphocytic Leukemia, run by Tesaro, Inc..
Trial summary
This is a four-part dose-escalation and confirmation study in participants with advanced solid tumors. Part A is for dose escalation and determination of maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of MK-4827. Part B is a prostate/ovarian cancer cohort expansion. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors, Chronic Lymphocytic Leukemia, T-cell-prolymphocytic Leukemia
- What is being tested?
- MK-4827
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 113 participants
- Where
- No sites listed yet
- Study dates
- Sep 2008to Jun 2013
- 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
- For Part A, participants must have a cytologically- or histologically-confirmed metastatic or locally advanced solid tumor for which standard therapy does not exist or the participants have refused standard therapy.
- For Part B, participants must have a cytologically- or histologically-confirmed locally advanced or metastatic prostate cancer for which standard therapy does not exist or the participants have refused standard therapy or sporadic (not known to have BRCA1 or BRCA2 gene mutations) recurrent platinum resistant high grade serous ovarian, primary peritoneal, or fallopian tube cancer. Participants who progressed while receiving a platinum-containing regimen are not eligible. Participants with ovarian cancer must have at least one measurable lesion (at least 15 mm in one dimension) or a cancer antigen (CA)-125 value twice the institutional upper limit of normal (ULN).
- For Part B, participants must have archival tumor tissue available.
- For Part C, participants must have a cytologically- or histologically-confirmed diagnosis of T-PLL or B-cell CLL. Participants with T- PLL must have progressed after receiving alemtuzumab. Participants with CLL must have been refractory to or progressed within 12 months following a fludarabine-containing regimen or have received at least 2 prior therapies (before or after the fludarabine containing regimen).
- For Part D, participants must have:
- a cytologically- or histologically-confirmed metastatic or locally advanced adenocarcinoma of the colon or rectum (mCRC) and evidence of phosphate and tensin homolog (PTEN) deficiency. Participants must have received at least 1 prior 5-fluoruracil (5-FU)-based combination chemotherapy regimen for mCRC, containing oxaliplatin or irinotecan. Participants must have measurable disease.
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- a cytologically- or histologically-confirmed persistent or recurrent endometrial carcinoma and measurable disease. Participants may not have had more than 1 prior chemotherapy regimen.
- a cytologically- or histologically-confirmed metastatic or locally advanced sporadic (not known to have a germline BRCA1 or BRCA2 mutation) partially platinum-sensitive recurrent epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer. Participants who cannot receive platinum due to allergy or toxicity are eligible. Participants with ovarian cancer may have received non-platinum containing chemotherapy between their last platinum-containing regimen and enrolling in this study. Participants must have measurable disease or an elevated CA-125 (at least 2 times the institutional upper limit of normal).
- a cytologically- or histologically-confirmed metastatic or locally advanced carcinoma of the breast that either lacks expression of the estrogen receptor (ER), progesterone receptor (PR) and HER2 (triple negative [TN]) or is ER and/or PR+ . Participants with locally advanced disease must have recurrent or progressive disease that is not suitable for treatment with curative intent. Participants with ER positive disease must have been treated with at least one line of hormonal therapy for recurrent/progressive disease or have been on hormonal therapy at the time of recurrence/progression. Participants with either ER+ or TN tumors may not have had more than 1 line of chemotherapy for treatment of recurrent disease. If participants received adjuvant chemotherapy they must have had a disease-free interval of at least 6 months from the completion of adjuvant chemotherapy. Participants must have measurable disease.
- Participant must have performance status ≤2 on the ECOG Performance Scale.
- Participant must have adequate organ function.
- Female participants of childbearing potential must have a negative pregnancy test within 72 hours prior to receiving the first dose of study medication.
- Participants with prostate cancer must continue on luteinizing-hormone-releasing hormone (LHRH) analogues if they have not had an orchiectomy to achieve a sustained baseline serum testosterone < 50 ng/dL.
Who cannot join
- Participant who has had chemotherapy, radiotherapy, hormonal or biological therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to first dose of study drug.
- Participant is currently participating or has participated in a study within 30 days or 5 half lives (which ever is longer) of administration of an investigational agent or within 30 days of participating in a study using an investigational device.
- Participants who have received bevacizumab may enter the trial 4 weeks after their last dose of bevacizumab if all bevacizumab-related toxicities have resolved.
- Participant with a history of a prior malignancy with the exception of cervical intraepithelial neoplasia; basal cell carcinoma of the skin; adequately treated localized prostate carcinoma with prostatic-specific antigen (PSA) <1.0; or who has undergone potentially curative therapy with no evidence of that disease for five years, or who is deemed at low risk for recurrence by his/her treating physician.
- Participants with known central nervous system (CNS) metastases and/or carcinomatous meningitis are excluded.
- Participant with a known primary central nervous system tumor.
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- Participant has known hypersensitivity to the components of study drug or its analogs.
- Participant has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Participant is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse.
- Participant is pregnant or breast feeding, or expecting to conceive or father children within the projected duration of the study.
- Participant is known to be Human Immunodeficiency Virus (HIV)-positive.
- Participant has known history of Hepatitis B or C.
- Participant has symptomatic ascites or a symptomatic pleural effusion.
- Participant has participated in a clinical trial with a known or putative PARP inhibitor.
- Participants with T-PLL or CLL with active autoimmune hemolytic anemia.
- Participants may not have had therapy with corticosteroids at greater than or equal to 20 mg/day prednisone equivalent within 2 weeks prior to the first dose of treatment.
About this study
Official title: A Phase I Study of MK-4827 in Patients With Advanced Solid Tumors or Hematologic Malignancies
This is a four-part dose-escalation and confirmation study in participants with advanced solid tumors. Part A is for dose escalation and determination of maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of MK-4827. Part B is a prostate/ovarian cancer cohort expansion. Part C is for a cohort of participants with relapsed or refractory T-cell prolymphocytic leukemia (T-PLL) or chronic lymphocytic leukemia (CLL). Part D will be for a cohort of participants with locally advanced or metastatic colorectal carcinoma (CRC), persistent or recurrent endometrial carcinoma, locally advanced or metastatic triple negative or highly proliferative estrogen receptor positive (ER+) breast cancer, or partially platinum-sensitive epithelial ovarian cancer. The study is also designed to find out whether MK-4827 causes at least 50% inhibition of poly adenosine diphosphate ribose polymerase (PARP) enzyme activity.
- Being tested
- MK-4827
- Keywords
- Neoplasms, Ovarian neoplasms, Prostatic neoplasms, Endocrine gland neoplasms, Ovarian diseases, Adnexal diseases, Genital diseases, female, Genital diseases, male, Genital neoplasms, female, Urogenital neoplasms, Endocrine system diseases, Gonadal disorders, Genital neoplasms, male, Prostatic diseases
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Prolymphocytic, T-Cell, Neoplasms, Ovarian Neoplasms, Prostatic Neoplasms, Endocrine Gland Neoplasms, Ovarian Diseases, Adnexal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-4827Drug
MK-4827 in 10 mg and 100 mg capsules given daily in a 21 day dosing cycle (dose escalation to RP2D).
| Study group | Role | What they receive |
|---|---|---|
| Part A-Dose escalation and confirmation | Experimental | Not described Receives: Drug: MK-4827 |
| Part B - Prostate/Ovarian Cancer Cohort | Experimental | Not described Receives: Drug: MK-4827 |
| Part C - T-PLL/CLL cohort | Experimental | Not described Receives: Drug: MK-4827 |
| Part D - CRC, endometrial, breast, and ovarian cancer cohort | Experimental | Not described Receives: Drug: MK-4827 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with dose limiting toxicities (DLTs)
Measured: Cycle 1 (21 days)
Percent inhibition of peripheral blood mononuclear cell PARP enzyme activity (Part A, B, and C)
Measured: Cycle 1 (Days 1-21)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2008 (estimated)
- Study startSep 2008
- Primary completionSep 2011
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for 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
- Single group
- Masking
- None (open label)
- Enrolment
- 113 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tesaro, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00749502
- Sponsor's protocol ID
- MK-4827-001
- Other IDs
- 2008_501
- Status last verified
- Jul 2013
- First submitted
- 5 Sep 2008
- Last updated
- 25 Jul 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Monk BJ, Romero I, Graybill W, Churruca C, O'Malley DM, Knudsen AO, Yap OWS, Baurain JF, Rose PG, Denys H, Ghamande S, Pisano C, Fabbro M, Braicu EI, Calvert PM, Amit A, Prendergast E, Taylor A, Kheibarshekan L, Zhang ZY, Zajic S, Jewell RC, Gupta D, Gonzalez-Martin A. Niraparib Population Pharmacokinetics and Exposure-Response Relationships in Patients With Newly Diagnosed Advanced Ovarian Cancer. Clin Ther. 2024 Aug;46(8):612-621. doi: 10.1016/j.clinthera.2024.06.001. Epub 2024 Jul 16.
PubMed 39019698Sandhu SK, Schelman WR, Wilding G, Moreno V, Baird RD, Miranda S, Hylands L, Riisnaes R, Forster M, Omlin A, Kreischer N, Thway K, Gevensleben H, Sun L, Loughney J, Chatterjee M, Toniatti C, Carpenter CL, Iannone R, Kaye SB, de Bono JS, Wenham RM. The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase 1 dose-escalation trial. Lancet Oncol. 2013 Aug;14(9):882-92. doi: 10.1016/S1470-2045(13)70240-7. Epub 2013 Jun 28.
PubMed 23810788Sandhu SK, Omlin A, Hylands L, Miranda S, Barber LJ, Riisnaes R, Reid AH, Attard G, Chen L, Kozarewa I, Gevensleben H, Campbell J, Fenwick K, Assiotis I, Olmos D, Yap TA, Fong P, Tunariu N, Koh D, Molife LR, Kaye S, Lord CJ, Ashworth A, de Bono J. Poly (ADP-ribose) polymerase (PARP) inhibitors for the treatment of advanced germline BRCA2 mutant prostate cancer. Ann Oncol. 2013 May;24(5):1416-8. doi: 10.1093/annonc/mdt074. Epub 2013 Mar 22. No abstract available.
PubMed 23524863
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of MK-4827 in Patients With Advanced Solid Tumors or Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT00749502
- Acronym / sponsor ID
- MK-4827-001
- Keywords
- Neoplasms, Ovarian neoplasms, Prostatic neoplasms, Endocrine gland neoplasms, Ovarian diseases, Adnexal diseases, Genital diseases, female, Genital diseases, male
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 113 participants (actual)
- Lead sponsor
- Tesaro, Inc.Industry (pharma, biotech, devices)
- Study start
- Sep 2008
- Primary completion
- Sep 2011 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 9 Sep 2008 (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.
This is a four-part dose-escalation and confirmation study in participants with advanced solid tumors. Part A is for dose escalation and determination of maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of MK-4827. Part B is a prostate/ovarian cancer cohort expansion. Part C is for a cohort of participants with relapsed or refractory T-cell prolymphocytic leukemia (T-PLL) or chronic lymphocytic leukemia (CLL). Part D will be for a cohort of participants with locally advanced or metastatic colorectal carcinoma (CRC), persistent or recurrent endometrial carcinoma, locally advanced or metastatic triple negative or highly proliferative estrogen receptor positive (ER+) breast cancer, or partially platinum-sensitive epithelial ovarian cancer. The study is also designed to find out whether MK-4827 causes at least 50% inhibition of poly adenosine diphosphate ribose polymerase (PARP) enzyme activity.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part A-Dose escalation and confirmation | Experimental | Drug: MK-4827 |
| Part B - Prostate/Ovarian Cancer Cohort | Experimental | Drug: MK-4827 |
| Part C - T-PLL/CLL cohort | Experimental | Drug: MK-4827 |
| Part D - CRC, endometrial, breast, and ovarian cancer cohort | Experimental | Drug: MK-4827 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- For Part A, participants must have a cytologically- or histologically-confirmed metastatic or locally advanced solid tumor for which standard therapy does not exist or the participants have refused standard therapy.
- For Part B, participants must have a cytologically- or histologically-confirmed locally advanced or metastatic prostate cancer for which standard therapy does not exist or the participants have refused standard therapy or sporadic (not known to have BRCA1 or BRCA2 gene mutations) recurrent platinum resistant high grade serous ovarian, primary peritoneal, or fallopian tube cancer. Participants who progressed while receiving a platinum-containing regimen are not eligible. Participants with ovarian cancer must have at least one measurable lesion (at least 15 mm in one dimension) or a cancer antigen (CA)-125 value twice the institutional upper limit of normal (ULN).
- For Part B, participants must have archival tumor tissue available.
- For Part C, participants must have a cytologically- or histologically-confirmed diagnosis of T-PLL or B-cell CLL. Participants with T- PLL must have progressed after receiving alemtuzumab. Participants with CLL must have been refractory to or progressed within 12 months following a fludarabine-containing regimen or have received at least 2 prior therapies (before or after the fludarabine containing regimen).
- For Part D, participants must have:
Key exclusion criteria (16 listed)
- Participant who has had chemotherapy, radiotherapy, hormonal or biological therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to first dose of study drug.
- Participant is currently participating or has participated in a study within 30 days or 5 half lives (which ever is longer) of administration of an investigational agent or within 30 days of participating in a study using an investigational device.
- Participants who have received bevacizumab may enter the trial 4 weeks after their last dose of bevacizumab if all bevacizumab-related toxicities have resolved.
- Participant with a history of a prior malignancy with the exception of cervical intraepithelial neoplasia; basal cell carcinoma of the skin; adequately treated localized prostate carcinoma with prostatic-specific antigen (PSA) <1.0; or who has undergone potentially curative therapy with no evidence of that disease for five years, or who is deemed at low risk for recurrence by his/her treating physician.
- Participants with known central nervous system (CNS) metastases and/or carcinomatous meningitis are excluded.
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 |
|---|---|---|
| MK-4827MK-4827 in 10 mg and 100 mg capsules given daily in a 21 day dosing cycle (dose escalation to RP2D). | Drug | Part A-Dose escalation and confirmation, Part B - Prostate/Ovarian Cancer Cohort, Part C - T-PLL/CLL cohort, Part D - CRC, endometrial, breast, and ovarian cancer cohort |
Primary outcome
Number of participants with dose limiting toxicities (DLTs)
Time frame: Cycle 1 (21 days)
Percent inhibition of peripheral blood mononuclear cell PARP enzyme activity (Part A, B, and C)
Time frame: Cycle 1 (Days 1-21)
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 25 Jul 2013.
- Derived from this study: PubMed 39019698Monk BJ, Romero I, Graybill W, Churruca C, O'Malley DM, Knudsen AO, Yap OWS, Baurain JF, Rose PG, Denys H, Ghamande S, Pisano C, Fabbro M, Braicu EI, Calvert PM, Amit A, Prendergast E, Taylor A, Kheibarshekan L, Zhang ZY, Zajic S, Jewell RC, Gupta D, Gonzalez-Martin A. Niraparib Population Pharmacokinetics and Exposure-Response Relationships in Patients With Newly Diagnosed Advanced Ovarian Cancer. Clin Ther. 2024 Aug;46(8):612-621. doi: 10.1016/j.clinthera.2024.06.001. Epub 2024 Jul 16.
- Derived from this study: PubMed 23810788Sandhu SK, Schelman WR, Wilding G, Moreno V, Baird RD, Miranda S, Hylands L, Riisnaes R, Forster M, Omlin A, Kreischer N, Thway K, Gevensleben H, Sun L, Loughney J, Chatterjee M, Toniatti C, Carpenter CL, Iannone R, Kaye SB, de Bono JS, Wenham RM. The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase 1 dose-escalation trial. Lancet Oncol. 2013 Aug;14(9):882-92. doi: 10.1016/S1470-2045(13)70240-7. Epub 2013 Jun 28.
- Derived from this study: PubMed 23524863Sandhu SK, Omlin A, Hylands L, Miranda S, Barber LJ, Riisnaes R, Reid AH, Attard G, Chen L, Kozarewa I, Gevensleben H, Campbell J, Fenwick K, Assiotis I, Olmos D, Yap TA, Fong P, Tunariu N, Koh D, Molife LR, Kaye S, Lord CJ, Ashworth A, de Bono J. Poly (ADP-ribose) polymerase (PARP) inhibitors for the treatment of advanced germline BRCA2 mutant prostate cancer. Ann Oncol. 2013 May;24(5):1416-8. doi: 10.1093/annonc/mdt074. Epub 2013 Mar 22. No abstract available.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MK-4827 in people with Solid Tumors and Chronic Lymphocytic Leukemia, run by Tesaro, Inc..
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 13 inclusion and 16 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 25 Jul 2013. 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 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?
Number of participants with dose limiting toxicities (DLTs) (time frame: Cycle 1 (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?
On the ClinicalTrials.gov record for NCT00749502, which also lists 3 linked publications.
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 25 Jul 2013.