Advanced MelanomaPhase 2ADAPTeMNCT02663258
A Study of Anti-PD-1 (Pembrolizumab) Therapy in Metastatic Melanoma (ADAPTeM)
A Phase 2 study testing Pembrolizumab in people with Advanced Melanoma, run by Royal Marsden NHS Foundation Trust.
Trial summary
Abbreviated Title: An explorative Phase II study of Anti-PD-1 (Pembrolizumab) in patients with advanced melanoma (ADAPTeM) Trial Phase: Phase II Clinical Indication: Stage III unresectable/stage IV metastatic melanoma Trial Type: Exploratory Phase II trial Route of administration: Intravenous Pembrolizumab, 200mg… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Melanoma
- What is being tested?
- Pembrolizumab
- Type of treatment
- 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
- Jan 2016to 19 Jul 2017
- Phase
- Phase 2
- 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 metastatic melanoma (cutaneous or mucosal)
- Male or female, 18 years or older
- Presence of subcutaneous or lymph nodes metastases amenable to surgical core biopsy (as judged by an Oncological Surgical Consultant)
- Have measurable disease based on Response Evaluation Criteria in Solid Tumours (RECIST) 1.1.
- Have provided tissue from an archival tissue sample or newly obtained core biopsy of a tumour lesion.
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
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- Any number of previous lines of treatment for metastatic melanoma including treatment naïve patients.
- Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose 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 should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- Male subjects should 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.
- Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment.
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Who cannot join
- Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., Grade 1 or at baseline) from adverse events due to a previously administered agent.
- Note: Subjects with Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
- Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
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- Has a known additional malignancy that is progressing or requires active treatment.
- Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
- Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule.
- Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
- Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 or anti-CD137 antibody.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has received a live vaccine within 30 days prior to the first dose of trial treatment.
About this study
Official title: An Explorative Phase II Study of Anti-PD-1 (Pembrolizumab) Therapy in Metastatic Melanoma (ADAPTeM)
Abbreviated Title: An explorative Phase II study of Anti-PD-1 (Pembrolizumab) in patients with advanced melanoma (ADAPTeM)
Trial Phase: Phase II
Clinical Indication: Stage III unresectable/stage IV metastatic melanoma
Trial Type: Exploratory Phase II trial
Route of administration: Intravenous Pembrolizumab, 200mg, 3weekly
Trial Blinding: Unblinded; open label Phase II study
Treatment Groups: All participants treated with Pembrolizumab, 200mg iv, 3weekly
Number of trial subjects: 40
Estimated duration of trial: 24 months
Duration of Participation: 24 months
Read the detailed description
This is a single arm, single agent, open label, exploratory translational research study in patients with unresectable stage III or stage IV melanoma being treated with Pembrolizumab. Suitable patients will undergo serial surgical core biopsies (nonradiological) of subcutaneous or lymph node metastases (as judged by an Oncological Surgical Consultant). As a primary endpoint, the investigators will assess the safety and feasibility of undergoing these biopsies within the patient cohort. A total of forty patients will be recruited over a period of two years.
Patients who have provided consent and satisfied the eligibility criteria will undergo baseline CT scanning and peripheral blood sampling. At baseline, biopsies of suitable metastatic lesions will be undertaken and samples sent for histopathological assessment and analysis of molecular and immune parameters. Participants will be treated with Pembrolizumab, 200mg, intravenously, every 3 weeks. At 6 weeks following commencement of Pembrolizumab therapy, a further biopsy or excision of metastatic disease will be performed, unless considered no longer possible on the basis of a near or complete response to treatment. Blood sampling will be performed prior to each cycle and repeat CT scanning will occur every 9 weeks. Response evaluations will be performed according to RECIST 1.1 criteria. Pembrolizumab will be continued as long as study participants are deriving benefit and further biopsies of progressing lesions will be performed where possible.
The investigators aim to evaluate the safety and feasibility of obtaining serial tumour biopsies or excisions of metastatic disease during treatment with Pembrolizumab with exploration of the i) mechanistic activity of Pembrolizumab, ii) identification of intratumoural and peripheral factors limiting response, iii) identification of candidate predictive biomarker panels based on (i) and (ii) and iii) use of circulating free DNA (cfDNA) as a surrogate marker of response and guide to duration of therapy.
- Conditions
- Advanced Melanoma
- Being tested
- Pembrolizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab arm | Experimental | All participants treated with Pembrolizumab, 200mg iv, 3weekly Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
The percentage of patients that undergo serial core biopsies of metastatic lesions during treatment with Pembrolizumab
The primary endpoint of the study is to assess the feasibility of obtaining sequential tumour biopsies will be achieved when sequential biopsies (at baseline, week 6 and at disease progression), have successfully been carried out in a minimum of 75% of patients (i.e. 29 out of 40).The percentage of patients with complete tumour response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) will be tabulated. Associated 95% CI will be provided for response rates. The duration of objective response (for patients with CR and PR) will be defined as the time from initial CR or PR to the time of disease progression or death (whichever occurs first). For patients who do not die or experience PD, duration of objective response will be censored on the day of the last tumour assessment.
Measured: At study progression (average of 9 months) or 24 months after last patient enrolled
Secondary outcomes (4)
The complication rate associated with undergoing serial core biopsies
Complication rate will be defined as the proportion of patients who have hospital admission due to complication of biopsy e.g. infection/bleeding/pain control and/or delay in Pembrolizumab treatment due to complication of biopsy. This will be presented as a proportion with the 95% confidence interval.
Measured: At study progression (average of 9 months) or 24 months after last patient enrolled
Objective response rate
Objective response rate defined as proportion of patients with a best response of complete response (CR) or partial response (PR).
Measured: At study progression (average of 9 months) or 24 months after last patient enrolled
Progression free survival
Progression-free survival (PFS) will be defined as the time from the first day of Pembrolizumab treatment (cycle 1 day 1) until documented disease progression or death (whichever occurs first). Patients who do not have documented PD or death will be censored on the day of last tumour assessment (last follow-up).
Measured: At study progression (average of 9 months) or 24 months after last patient enrolled
Overall survival
Overall survival will be measured from the first day of treatment until death or last follow-up. Overall survival will be presented graphically using the Kaplan-Meier method. Median time to event and 95% CI will be estimated from the Kaplan-Meier curves.
Measured: At study progression (average of 9 months) or 24 months after last patient enrolled
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2016 (estimated)
- Study startJan 2016
- Primary completion19 Jul 2017
- Study completion19 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced MelanomaStudies of the same condition, open and under way.
- More trials run by Royal Marsden NHS Foundation TrustThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royal Marsden NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- James Larkin, Principal investigator, Royal Marsden NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02663258
- Sponsor's protocol ID
- CCR4254
- Acronym
- ADAPTeM
- Status last verified
- Jan 2016
- First submitted
- 12 Jan 2016
- Last updated
- 1 Aug 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Explorative Phase II Study of Anti-PD-1 (Pembrolizumab) Therapy in Metastatic Melanoma (ADAPTeM)
- ClinicalTrials.gov ID
- NCT02663258
- Acronym / sponsor ID
- ADAPTeM / CCR4254
- Conditions
- Advanced Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Royal Marsden NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Jan 2016
- Primary completion
- 19 Jul 2017 (actual)
- Study completion
- 19 Jul 2017 (actual)
- First posted
- 26 Jan 2016 (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.
Abbreviated Title: An explorative Phase II study of Anti-PD-1 (Pembrolizumab) in patients with advanced melanoma (ADAPTeM)
Trial Phase: Phase II
Clinical Indication: Stage III unresectable/stage IV metastatic melanoma
Trial Type: Exploratory Phase II trial
Route of administration: Intravenous Pembrolizumab, 200mg, 3weekly
Trial Blinding: Unblinded; open label Phase II study
Treatment Groups: All participants treated with Pembrolizumab, 200mg iv, 3weekly
Number of trial subjects: 40
Estimated duration of trial: 24 months
Duration of Participation: 24 months
Detailed description
This is a single arm, single agent, open label, exploratory translational research study in patients with unresectable stage III or stage IV melanoma being treated with Pembrolizumab. Suitable patients will undergo serial surgical core biopsies (nonradiological) of subcutaneous or lymph node metastases (as judged by an Oncological Surgical Consultant). As a primary endpoint, the investigators will assess the safety and feasibility of undergoing these biopsies within the patient cohort. A total of forty patients will be recruited over a period of two years.
Patients who have provided consent and satisfied the eligibility criteria will undergo baseline CT scanning and peripheral blood sampling. At baseline, biopsies of suitable metastatic lesions will be undertaken and samples sent for histopathological assessment and analysis of molecular and immune parameters. Participants will be treated with Pembrolizumab, 200mg, intravenously, every 3 weeks. At 6 weeks following commencement of Pembrolizumab therapy, a further biopsy or excision of metastatic disease will be performed, unless considered no longer possible on the basis of a near or complete response to treatment. Blood sampling will be performed prior to each cycle and repeat CT scanning will occur every 9 weeks. Response evaluations will be performed according to RECIST 1.1 criteria. Pembrolizumab will be continued as long as study participants are deriving benefit and further biopsies of progressing lesions will be performed where possible.
The investigators aim to evaluate the safety and feasibility of obtaining serial tumour biopsies or excisions of metastatic disease during treatment with Pembrolizumab with exploration of the i) mechanistic activity of Pembrolizumab, ii) identification of intratumoural and peripheral factors limiting response, iii) identification of candidate predictive biomarker panels based on (i) and (ii) and iii) use of circulating free DNA (cfDNA) as a surrogate marker of response and guide to duration of therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab arm | Experimental | Drug: PembrolizumabAll participants treated with Pembrolizumab, 200mg iv, 3weekly |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically confirmed metastatic melanoma (cutaneous or mucosal)
- Male or female, 18 years or older
- Presence of subcutaneous or lymph nodes metastases amenable to surgical core biopsy (as judged by an Oncological Surgical Consultant)
- Have measurable disease based on Response Evaluation Criteria in Solid Tumours (RECIST) 1.1.
- Have provided tissue from an archival tissue sample or newly obtained core biopsy of a tumour lesion.
Key exclusion criteria (20 listed)
- Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., Grade 1 or at baseline) from adverse events due to a previously administered agent.
- Has a known additional malignancy that is progressing or requires active treatment.
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 |
|---|---|---|
| PembrolizumabAlso: Keytruda | Drug | Pembrolizumab arm |
Primary outcome
The percentage of patients that undergo serial core biopsies of metastatic lesions during treatment with Pembrolizumab
Time frame: At study progression (average of 9 months) or 24 months after last patient enrolled
The primary endpoint of the study is to assess the feasibility of obtaining sequential tumour biopsies will be achieved when sequential biopsies (at baseline, week 6 and at disease progression), have successfully been carried out in a minimum of 75% of patients (i.e. 29 out of 40).The percentage of patients with complete tumour response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) will be tabulated. Associated 95% CI will be provided for response rates. The duration of objective response (for patients with CR and PR) will be defined as the time from initial CR or PR to the time of disease progression or death (whichever occurs first). For patients who do not die or experience PD, duration of objective response will be censored on the day of the last tumour assessment.
4 secondary outcomes
The complication rate associated with undergoing serial core biopsies
Time frame: At study progression (average of 9 months) or 24 months after last patient enrolled
Objective response rate
Time frame: At study progression (average of 9 months) or 24 months after last patient enrolled
Progression free survival
Time frame: At study progression (average of 9 months) or 24 months after last patient enrolled
Overall survival
Time frame: At study progression (average of 9 months) or 24 months after last patient enrolled
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 1 Aug 2017.
- 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.
James Larkin principal investigator
Royal Marsden NHS Foundation Trust
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab in people with Advanced Melanoma, run by Royal Marsden NHS Foundation Trust.
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 12 inclusion and 20 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 1 Aug 2017. 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 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?
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?
The percentage of patients that undergo serial core biopsies of metastatic lesions during treatment with Pembrolizumab (time frame: At study progression (average of 9 months) or 24 months after last patient enrolled). 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 1 Aug 2017.