Assess the Efficacy of Pembrolizumab Plus Radiotherapy or Ablation in Metastatic Colorectal Cancer Patients

NCT02437071 | Completed Phase 2 Results

• 1 other identifier: 15-069
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The radiation therapy or ablation that the patient received as standard therapy treated only the tumors that were radiated or ablated. Radiation therapy or ablation plus pembrolizumab might lead to a stronger immune response that may control or destroy tumors that did not receive radiation therapy or ablation. The purpose of this study is to find out what effects, good and/or bad, pembrolizumab has on the patient, and the cancer that did not receive radiation therapy or ablation.

Conditions

Metastatic Colorectal Cancer

Keywords

Radiotherapy; Ablation; Pembrolizumab; 15-069; Metastatic Colorectal Cancer Patients

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Response

  If at the end of the study ≥3 tumor responses per RECIST 1.1 are observed in a cohort, then further investigation of pembrolizumab plus RT and/or pembrolizumab plus ablation will be considered worthwhile. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD) no PR - no Progressive Disease (PD); Progressive Disease (PD) \>=20% increase sum of longest diameters of the target lesions (SLD) compared to smallest SLD in study or progression of non-target lesions or new lesions

  approximately 9 weeks

Secondary Outcomes (1)

• Number of Participants With Toxicities

  2 years

Study Arms (2)

Pembrolizumab Plus Radiotherapy

EXPERIMENTAL

pembrolizumab plus RT in subjects with metastatic CRC who are undergoing RT as standard therapy

Drug: Pembrolizumab; Radiation: Radiotherapy

Pembrolizumab Plus Ablation

EXPERIMENTAL

pembrolizumab plus ablation in subjects with metastatic CRC who are undergoing ablation as standard therapy

Drug: Pembrolizumab; Procedure: Radiofrequency ablation

Interventions

Pembrolizumab DRUG

Pembrolizumab will be administered as a 30 minute IV infusion (every effort should be made to target infusion timing to be as close to 30 minutes as possible. However, given the variability of infusion pumps from site to site, a window of -5 minutes and +10 minutes is permitted (i.e., infusion time is 30 minutes: -5 min/+10 min).

Pembrolizumab Plus Ablation; Pembrolizumab Plus Radiotherapy

Radiotherapy RADIATION

Pembrolizumab Plus Radiotherapy

Radiofrequency ablation PROCEDURE

Pembrolizumab Plus Ablation

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Histologically- or cytologically- confirmed CRC.
• Metastatic or recurrent CRC
• Subjects have received two or more standard available therapies known to prolong survival and for which they would be considered eligible. Such therapies should include regimens containing oxaliplatin and irinotecan in combination with a fluoropyrimidine if appropriate (e.g., FOLFOX and FOLFIRI or their variants).
• At least one tumor for which palliative RT is considered appropriate standard therapy (cohort 1); or, at least one tumor for which palliative ablation is considered appropriate standard therapy (cohort 2).
• At least one index lesion that will not undergo RT or ablation, and which is measurable based on RECIST 1.1.
• Be ≥ 18 years of age on day of signing informed consent. Consent for tumor biopsies and blood draws for research purposes.
• Consent for use of available archived tissue for research purposes.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• Demonstrate adequate organ function as defined in Table 6.1, all screening labs should be performed within 6 weeks of treatment initiation.
• Hematological
• Absolute neutrophil count (ANC) ≥1,500 /mcL
• Platelets ≥100,000 / mcL Renal
• Serum creatinine OR Measured or calculated\* creatinine clearance (GFR can also be used in place of creatinine or CrCl)
• ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN Hepatic

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 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.
• 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.
• 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, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• Mendonca Gorgulho C, Krishnamurthy A, Lanzi A, Galon J, Housseau F, Kaneno R, Lotze MT. Gutting it Out: Developing Effective Immunotherapies for Patients With Colorectal Cancer. J Immunother. 2021 Feb-Mar 01;44(2):49-62. doi: 10.1097/CJI.0000000000000357.

  PMID: 33416261 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

pembrolizumab; Radiotherapy; Radiofrequency Ablation

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Radiofrequency Therapy; Ablation Techniques; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Neil Segal, MD, PhD
• Organization: Memorial Sloan Kettering Cancer Center

segaln@mskcc.org

646-888-4187

Study Officials

• Neil Segal, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2015
• First Posted: May 7, 2015
• Study Start: April 1, 2015
• Primary Completion: September 20, 2024
• Study Completion: September 20, 2024
• Last Updated: December 5, 2025
• Results First Posted: December 5, 2025

Record last verified: 2024-09

Locations

US (1)