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Pembrolizumab and Palliative Radiotherapy in Lung (PEAR)

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ClinicalTrials.gov Identifier: NCT02587455
Recruitment Status : Active, not recruiting
First Posted : October 27, 2015
Last Update Posted : April 29, 2020
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Institute of Cancer Research, United Kingdom
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
Royal Marsden NHS Foundation Trust

Brief Summary:

Lung cancer is the second most common cancer in the UK with around 43,500 new patients diagnosed each year. About 69% of patients are diagnosed with advanced stage disease and at present these patients would be expected to survive for less than 12 months. These statistics therefore show the need for the development of new effective drugs in the treatment of advanced Lung cancer.

Recent trial results have shown the efficacy of immunotherapy in treating several types of tumours including lung cancer. These tumours are known to express a high level of a glycoprotein called PDL1 which is a component of the PD1 pathway. In cancer the PD1 pathway can be hijacked by tumours leading to the immune system being suppressed. The aim of the new drug Pembrolizumab is to restart the PD1 pathway and use the immune system to help fight the cancer cells. Radiotherapy has also been shown to cause cancer to increase production of the proteins that can block the immune system. Therefore it has been proposed that combine of new immunotherapy agent such as pembrolizumab and radiotherapy in the treatment of lung cancer will allow more cancer cells to be killed through the immune system.

The purpose of this study is to see if pembrolizumab can safety be combined with standard palliative radiotherapy in patients with lung cancer. In addition once the patients have completed their course of radiotherapy they will remain on pembrolizumab alone and the study will look at how well this treatment regimen can control the growth of the cancer.


Condition or disease Intervention/treatment Phase
Thoracic Tumours Drug: Pembrolizumab Radiation: Radiotherapy Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Phase I Dose Escalation of pAlliative Radiotherapy With Anti-PD1 Antibody Pembrolizumab in Thoracic Tumours
Study Start Date : June 2016
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Palliative Care

Arm Intervention/treatment
Experimental: Low Dose Radiotherapy Arm
Pembrolizumab and radiotherapy
Drug: Pembrolizumab
Pembrolizumab - Trial Treatment
Other Name: MK-3475/pembrolizumab (KEYTRUDA®)

Radiation: Radiotherapy
Radiotherapy - Standard Treatment

Experimental: High Dose Radiotherapy Arm
Pembrolizumab and radiotherapy
Drug: Pembrolizumab
Pembrolizumab - Trial Treatment
Other Name: MK-3475/pembrolizumab (KEYTRUDA®)

Radiation: Radiotherapy
Radiotherapy - Standard Treatment




Primary Outcome Measures :
  1. Toxicity rate of DLTs assessed by CTCAEv4 [ Time Frame: two months after the last fraction of RT has been administered ]
  2. Maximum tolerated dose (MTD) of pembrolizumab that can be safely combined with radiotherapy (RT) in the absence of dose limiting toxicity (DLT) assessed by CTCAEv4 [ Time Frame: up to 24 months ]

Secondary Outcome Measures :
  1. Progression free survival rates will be calculated at 6 and 12 months, respectively [ Time Frame: 6 and 12 months ]
  2. Overall survival rates will be calculated at 6 and 12 months, respectively [ Time Frame: 6 and 12 months ]
  3. Progression free survival rates will be calculated at 6 and 12 months for PDL-1 strong patients, respectively [ Time Frame: 6 and 12 months ]
  4. Overall survival rates will be calculated at 6 and 12 months for PDL-1 strong patients, respectively [ Time Frame: 6 and 12 months ]
  5. Duration of clinical benefit, as assessed by RECIST v1.1 [ Time Frame: 6 months and 1 year ]
  6. Compare response rates, as assessed by RECIST v1.1, between squamous and non-squamous histological sub-types [ Time Frame: 6 months and 1 year ]

Other Outcome Measures:
  1. Assessing individual lesion response (CR/PR/PD/SD) determined by RECIST v1.1 to evaluate the abscopal effect between pembrolizumab and RT [ Time Frame: cycle 2 (week 8/9) and cycle 5 (week 17/18) ]
  2. Identify biomarkers and correlate with clinical benefit, as defined by RECIST v1.1 [ Time Frame: through study completion (24 months) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Be willing and able to provide written informed consent for the trial.
  2. Have measurable disease based on RECIST 1.1.
  3. Histologically verified NSCLC including squamous cell carcinoma, adenocarcinoma, adenosquamous or large cell anaplastic carcinoma; requiring palliative radiotherapy for which no curative therapy exists will be recruited into the trial.
  4. Patients are permitted to have extrathoracic disease which will not be encompassed in the radiotherapy field. This disease will be assessed for abscopal response
  5. Ability to tolerate a course of palliative radiotherapy to the lung.
  6. Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumour lesion.
  7. Have a performance status of 0-2 on the ECOG Performance Scale.
  8. Demonstrate adequate organ function, all screening labs should be performed within 10 days of confirmation of eligibility.
  9. Patient's lung function tests at baseline should have an FEV1 > 0.8L or > 30%.
  10. See protocol section.

Exclusion Criteria:

  1. 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.
  2. 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.
  3. 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.
  4. Previous radiotherapy to the lung
  5. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy 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 a previously administered agent.

    Note: Patients with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.

    Note: If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.

  6. 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.
  7. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients 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.
  8. 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. Patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Patients that require the use of bronchodilators or local steroid injections would not be excluded from the study. Patients with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
  9. Has evidence of interstitial lung disease or active, noninfectious pneumonitis.
  10. Has received prior therapy with an antiPD1, antiPDL1, antiPDL2, antiCD137, or anti Cytotoxic T-lymphocyte associated antigen4 (CTLA4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways).
  11. See protocol section.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02587455


Locations
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United Kingdom
NIHR Biomedical Research Centre at RM and ICR (https://www.cancerbrc.org/)
London, United Kingdom, SW3 6JJ
NIHR Biomedical Research Centre at RM and ICR (https://www.cancerbrc.org/)
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Royal Marsden NHS Foundation Trust
Merck Sharp & Dohme Corp.
Institute of Cancer Research, United Kingdom
National Institute for Health Research, United Kingdom
Investigators
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Study Director: Dr Merina Ahmed Consultant Clinical Oncologist
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Responsible Party: Royal Marsden NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT02587455    
Other Study ID Numbers: CCR 4282
First Posted: October 27, 2015    Key Record Dates
Last Update Posted: April 29, 2020
Last Verified: April 2020
Keywords provided by Royal Marsden NHS Foundation Trust:
Non-small cell carcinoma
Additional relevant MeSH terms:
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Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents