A Study of Anti-PD-1 (Pembrolizumab) Therapy in Metastatic Melanoma (ADAPTeM)

NCT02663258 | Withdrawn Phase 2 DMC

• 1 other identifier: CCR4254
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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, 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

Conditions

Advanced Melanoma

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  At study progression (average of 9 months) or 24 months after last patient enrolled

• Objective response rate

  At study progression (average of 9 months) or 24 months after last patient enrolled

• Progression free survival

  At study progression (average of 9 months) or 24 months after last patient enrolled

• Overall survival

  At study progression (average of 9 months) or 24 months after last patient enrolled

Study Arms (1)

Pembrolizumab arm

EXPERIMENTAL

All participants treated with Pembrolizumab, 200mg iv, 3weekly

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Also known as: Keytruda

Pembrolizumab arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead
• Merck Sharp & Dohme LLC: collaborator

MeSH Terms

Interventions

pembrolizumab

Study Officials

• James Larkin

  Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2016
• First Posted: January 26, 2016
• Study Start: January 1, 2016
• Primary Completion: July 19, 2017
• Study Completion: July 19, 2017
• Last Updated: August 1, 2017

Record last verified: 2016-01

Data Sharing

• IPD Sharing: Will not share