Cervical CancerPhase 1/2NCT01076400
A Study of Adavosertib (MK-1775) in Combination With Topotecan/Cisplatin in Participants With Cervical Cancer (MK-1775-008)
A Phase 1/2 study testing adavosertib, Topotecan and Cisplatin in people with Cervical Cancer, run by Merck Sharp & Dohme LLC.
Trial summary
This study will be conducted in two parts. Part 1 will determine whether administration of adavosertib in combination with topotecan and cisplatin is generally well-tolerated and causes clinical objective responses in patients with cervical cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Cervical Cancer
- What is being tested?
- adavosertib, Topotecan and Cisplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7 participants
- Where
- No sites listed yet
- Study dates
- 31 May 2010to 13 Jun 2011
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has advanced, metastatic, and recurrent squamous cell, adenosquamous, or adeno-carcinoma of the uterine cervix (Stage II - IVb)
- Has received cisplatin in combination with radiation as initial or adjuvant treatment for their cervical cancer
- Has not received any other treatment for their cancer following the cisplatin-based chemo-radiation or targeted therapy except non-cytotoxic targeted therapy
- Recurrence must be at least 6 months post cisplatin-based chemotherapy
- Has measurable disease
- Performance status on the Eastern Cooperative Oncology Group (ECOG) Performance Scale is less than or equal to 1
- Has a negative pregnancy test within 72 hours of the first dose of study medication
Who cannot join
- Has had chemotherapy, radiotherapy, or biological therapy within 6 months of entering the study
- Has a history of vascular thrombotic events or vascular reconstruction
- Has active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has a primary CNS tumor
- Requires the use of medications or products that are metabolized by, or inhibit or induce CYP3A4 (Cytochrome P450 3A4)
- Is expecting to reproduce within the duration of the study or is pregnant or breastfeeding
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- Is known to be Human Immunodeficiency Virus (HIV)-positive
- Has known active Hepatitis B or C
- Has a known history of interstitial lung disease or pulmonary fibrosis
- Has symptomatic ascites or pleural effusion
- Has a clinical history suggestive of Li-Fraumeni Syndrome
About this study
Official title: A Two Part, Phase I-IIa Study Evaluating MK1775 in Combination With Topotecan/Cisplatin in Adult Patients With Cervical Cancer
This study will be conducted in two parts. Part 1 will determine whether administration of adavosertib in combination with topotecan and cisplatin is generally well-tolerated and causes clinical objective responses in patients with cervical cancer. Part 1 will also define the recommended Phase 2 dose and maximum tolerated dose (MTD) of the combination of adavosertib with topotecan and cisplatin. Part 2 of the study will evaluate whether treatment with adavosertib in combination with topotecan and cisplatin causes an improvement in progression-free survival (PFS) compared to treatment with topotecan and cisplatin alone and will further evaluate the tolerability of the combination treatment. The primary hypothesis is the combination of adavosertib, topotecan and cisplatin causes objective radiological responses (assessed per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria) in ≥30% of participants. Due to the early termination of the study by the sponsor, no participants were enrolled in Part 2 of the study.
- Conditions
- Cervical Cancer
- Medical subject headings
- Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
adavosertibDrug
Also called MK-1775
Adavosertib capsules are administered in sequentially rising dose levels twice daily for a total of nine doses on Days 1-5 of a 21-day cycle.
TopotecanDrug
Topotecan is administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3.
CisplatinDrug
Cisplatin is administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 1.
Placebo to adavosertibDrug
Placebo to adavosertib capsules are administered in sequentially rising dose levels twice daily for a total of nine doses on Days 1-5 of a 21-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: adavosertib + topotecan/cisplatin | Experimental | Part 1: Dose escalation study. adavosertib capsules will be administered in sequentially rising dose levels twice daily for a total of nine doses on Days 1-5 of a 21-day cycle. Topotecan will be administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3 . Cisplatin will be administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 1. Receives: Drug: adavosertib; Drug: Topotecan; Drug: Cisplatin |
| Part 2: adavosertib + topotecan/cisplatin | Experimental | Part 2: adavosertib capsules will be administered at the dose determined in Part 1 twice daily for a total of nine doses on Days 1-5 of a 21-day cycle. Topotecan will be administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3. Cisplatin will be administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 1. Receives: Drug: adavosertib; Drug: Topotecan; Drug: Cisplatin |
| Part 2: Placebo to adavosertib + topotecan/cisplatin | Placebo comparator | Part 2: Placebo to adavosertib capsules will be administered twice daily for a total of nine doses on Days 1-5 of a 21-day cycle. Topotecan will be administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3. Cisplatin will be administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 1. Receives: Drug: Topotecan; Drug: Cisplatin; Drug: Placebo to adavosertib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Percentage of Participants Whose Best Confirmed Response is Partial Response (PR) or Complete Response (CR)
On the basis of Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, PR is at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline sum diameters. CR is the disappearance of all extranodal target lesions, where all pathological lymph nodes must have decreased to <10 mm in the short axis.
Measured: Up to approximately 1 year
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
A DLT is a protocol-defined, (hematologic and non-hematologic), AE that must be definitely, probably, or possibly related to the study therapy. A DLT is any of the following: Grade 4-5 hematological toxicity; Grade 3 or Grade 4 neutropenia with fever >38.°C and/or infection requiring antibiotic or anti-fungal treatment. Non-hematologic dose-limiting toxicities are any Grade 3, 4, or 5 non-hematologic toxicity, with specific exceptions. If occurring within the first cycle of combination therapy: unresolved drug-related toxicity, preventing (re) treatment for 3 weeks or more from the date of the next scheduled treatment or any drug-related toxicity preventing the participant from taking at least 75% of the doses of MK-1775 with each administration of chemotherapy.
Measured: Up to approximately 1 year
Part 2: Length of Time for Progression-free Survival (PFS)
PFS is the length of time during and after treatment that a participant lives, but whose tumor progression does not worsen. PFS is defined as the time from randomization to progressive disease or death, whichever occurs earlier. Tumor volume changes of +20% for progressive disease was used to be consistent with RECIST 1.1.
Measured: Up to approximately 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2010 (estimated)
- Study start31 May 2010
- Primary completion13 Jun 2011
- Study completion13 Jun 2011
Why it stopped: The sponsor permanently suspended new enrollment into the trial and discontinued the study; which was not related to any concerns over product safety.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cervical CancerStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01076400
- Sponsor's protocol ID
- 1775-008
- Other IDs
- MK-1775-008, 2009-017054-12, 2009
- Status last verified
- Aug 2023
- First submitted
- 24 Feb 2010
- Last updated
- 18 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two Part, Phase I-IIa Study Evaluating MK1775 in Combination With Topotecan/Cisplatin in Adult Patients With Cervical Cancer
- ClinicalTrials.gov ID
- NCT01076400
- Acronym / sponsor ID
- 1775-008
- Conditions
- Cervical Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The sponsor permanently suspended new enrollment into the trial and discontinued the study; which was not related to any concerns over product safety.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 31 May 2010 (actual)
- Primary completion
- 13 Jun 2011 (actual)
- Study completion
- 13 Jun 2011 (actual)
- First posted
- 26 Feb 2010 (estimated)
- Results
- Posted 14 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will be conducted in two parts. Part 1 will determine whether administration of adavosertib in combination with topotecan and cisplatin is generally well-tolerated and causes clinical objective responses in patients with cervical cancer. Part 1 will also define the recommended Phase 2 dose and maximum tolerated dose (MTD) of the combination of adavosertib with topotecan and cisplatin. Part 2 of the study will evaluate whether treatment with adavosertib in combination with topotecan and cisplatin causes an improvement in progression-free survival (PFS) compared to treatment with topotecan and cisplatin alone and will further evaluate the tolerability of the combination treatment. The primary hypothesis is the combination of adavosertib, topotecan and cisplatin causes objective radiological responses (assessed per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria) in ≥30% of participants. Due to the early termination of the study by the sponsor, no participants were enrolled in Part 2 of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part 1: adavosertib + topotecan/cisplatin | Experimental | Drug: adavosertib, Drug: Topotecan, Drug: CisplatinPart 1: Dose escalation study. adavosertib capsules will be administered in sequentially rising dose levels twice daily for a total of nine doses on Days 1-5 of a 21-day cycle. Topotecan will be administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3 . Cisplatin will be administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 1. |
| Part 2: adavosertib + topotecan/cisplatin | Experimental | Drug: adavosertib, Drug: Topotecan, Drug: CisplatinPart 2: adavosertib capsules will be administered at the dose determined in Part 1 twice daily for a total of nine doses on Days 1-5 of a 21-day cycle. Topotecan will be administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3. Cisplatin will be administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 1. |
| Part 2: Placebo to adavosertib + topotecan/cisplatin | Placebo comparator | Drug: Topotecan, Drug: Cisplatin, Drug: Placebo to adavosertibPart 2: Placebo to adavosertib capsules will be administered twice daily for a total of nine doses on Days 1-5 of a 21-day cycle. Topotecan will be administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3. Cisplatin will be administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 1. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Has advanced, metastatic, and recurrent squamous cell, adenosquamous, or adeno-carcinoma of the uterine cervix (Stage II - IVb)
- Has received cisplatin in combination with radiation as initial or adjuvant treatment for their cervical cancer
- Has not received any other treatment for their cancer following the cisplatin-based chemo-radiation or targeted therapy except non-cytotoxic targeted therapy
- Recurrence must be at least 6 months post cisplatin-based chemotherapy
- Has measurable disease
Key exclusion criteria (11 listed)
- Has had chemotherapy, radiotherapy, or biological therapy within 6 months of entering the study
- Has a history of vascular thrombotic events or vascular reconstruction
- Has active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has a primary CNS tumor
- Requires the use of medications or products that are metabolized by, or inhibit or induce CYP3A4 (Cytochrome P450 3A4)
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 |
|---|---|---|
| adavosertibAlso: MK-1775Adavosertib capsules are administered in sequentially rising dose levels twice daily for a total of nine doses on Days 1-5 of a 21-day cycle. | Drug | Part 1: adavosertib + topotecan/cisplatin, Part 2: adavosertib + topotecan/cisplatin |
| TopotecanTopotecan is administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3. | Drug | Part 1: adavosertib + topotecan/cisplatin, Part 2: Placebo to adavosertib + topotecan/cisplatin, Part 2: adavosertib + topotecan/cisplatin |
| CisplatinCisplatin is administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 1. | Drug | Part 1: adavosertib + topotecan/cisplatin, Part 2: Placebo to adavosertib + topotecan/cisplatin, Part 2: adavosertib + topotecan/cisplatin |
| Placebo to adavosertibPlacebo to adavosertib capsules are administered in sequentially rising dose levels twice daily for a total of nine doses on Days 1-5 of a 21-day cycle. | Drug | Part 2: Placebo to adavosertib + topotecan/cisplatin |
Primary outcome
Part 1: Percentage of Participants Whose Best Confirmed Response is Partial Response (PR) or Complete Response (CR)
Time frame: Up to approximately 1 year
On the basis of Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, PR is at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline sum diameters. CR is the disappearance of all extranodal target lesions, where all pathological lymph nodes must have decreased to <10 mm in the short axis.
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: Up to approximately 1 year
A DLT is a protocol-defined, (hematologic and non-hematologic), AE that must be definitely, probably, or possibly related to the study therapy. A DLT is any of the following: Grade 4-5 hematological toxicity; Grade 3 or Grade 4 neutropenia with fever >38.°C and/or infection requiring antibiotic or anti-fungal treatment. Non-hematologic dose-limiting toxicities are any Grade 3, 4, or 5 non-hematologic toxicity, with specific exceptions. If occurring within the first cycle of combination therapy: unresolved drug-related toxicity, preventing (re) treatment for 3 weeks or more from the date of the next scheduled treatment or any drug-related toxicity preventing the participant from taking at least 75% of the doses of MK-1775 with each administration of chemotherapy.
Part 2: Length of Time for Progression-free Survival (PFS)
Time frame: Up to approximately 1 year
PFS is the length of time during and after treatment that a participant lives, but whose tumor progression does not worsen. PFS is defined as the time from randomization to progressive disease or death, whichever occurs earlier. Tumor volume changes of +20% for progressive disease was used to be consistent with RECIST 1.1.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Merck Clinical Trial InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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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.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing adavosertib, Topotecan and Cisplatin in people with Cervical Cancer, run by Merck Sharp & Dohme LLC.
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 7 inclusion and 11 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 18 Sep 2023. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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: Percentage of Participants Whose Best Confirmed Response is Partial Response (PR) or Complete Response (CR) (time frame: Up to approximately 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?
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 18 Sep 2023; AzTrials last refreshed its copy on 7 Nov 2026.