Clinical Trials /

PI Pembro in Combination With Stereotactic Body Radiotherapy for Liver Metastatic Colorectal Cancer

NCT02837263

Description:

The purpose of this research study is: - To find out how safe the study drug, pembrolizumab, is when combined with stereotactic body radiotherapy (SBRT) to the liver. - To see how well subjects can tolerate treatment with pembrolizumab and SBRT. - To find out how often colorectal cancer comes back 1 year after surgically removing all known disease and being treated with SBRT and pembrolizumab.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: PI Pembro in Combination With Stereotactic Body Radiotherapy for Liver Metastatic Colorectal Cancer
  • Official Title: Pembrolizumab in Combination With Stereotactic Body Radiotherapy for Liver Metastatic Colorectal Cancer

Clinical Trial IDs

  • ORG STUDY ID: UW15063
  • SECONDARY ID: P30CA014520
  • SECONDARY ID: NCI-2016-01077
  • SECONDARY ID: 2016-0303
  • NCT ID: NCT02837263

Conditions

  • Colorectal Cancer
  • Colorectal Adenocarcinoma
  • Stage IVA Colorectal Cancer
  • Stage IVB Colorectal Cancer
  • Metastatic Carcinoma in the Liver

Interventions

DrugSynonymsArms
PembrolizumabPembro, KeytrudaSBRT + Pembrolizumab

Purpose

The purpose of this research study is: - To find out how safe the study drug, pembrolizumab, is when combined with stereotactic body radiotherapy (SBRT) to the liver. - To see how well subjects can tolerate treatment with pembrolizumab and SBRT. - To find out how often colorectal cancer comes back 1 year after surgically removing all known disease and being treated with SBRT and pembrolizumab.

Detailed Description

      This is a phase 1b feasibility study to evaluate the use of PD-1 blockade in combination with
      ablative radiotherapy for the treatment of metastatic colorectal cancer (CRC). This study
      will examine the sequential combination of stereotactic body radiotherapy (SBRT) and
      pembrolizumab for patients for whom the goal is eradicating all known sites of disease. It is
      very likely that for many patients the SBRT therapy will be completed following other
      modalities including operative resection or ablation.
    

Trial Arms

NameTypeDescriptionInterventions
SBRT + PembrolizumabExperimentalSubjects will receive stereotactic body radiotherapy (SBRT) within 4 weeks of enrollment. Following SBRT, subjects will receive one cycle of pre-operative pembrolizumab given as an IV over approximately 30 minutes. Surgical management to remove all known sites of metastatic disease should occur 2 weeks post pembrolizumab treatment. Approximately 4-8 weeks after surgery subjects will being the second phase of pembrolizumab treatment. They will receive this treatment every 3 weeks (cycle) for 8 more cycles after surgery. Prior to the 5th cycle of pembrolizumab subjects will also have tumor imaging (CT or MRI).
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Willing and able to provide written informed consent/assent for the trial

          -  Be >/= 18 years of age on day of signing consent.

          -  Have a diagnosis of histologically confirmed metastatic colorectal cancer to the liver
             (no other sites of metastatic disease)

             * Histologic confirmation of a colorectal primary tumor is acceptable if accompanied
             by radiographic evidence of metastatic disease

          -  Tumor must be mismatch repair (MMR) proficient as determined by microsatellite
             instability or immunohistochemistry for for MMR proteins

               -  Microsatellite instability testing must be MSI-stable or MSI-low

               -  Or IHC for MMR proteins must demonstrate intact MMR proteins

          -  Participant must be candidate for SBRT to at least one intrahepatic lesion. There is
             no limit on the number of intrahepatic lesions the patient may have

          -  Participant must be a surgical candidate with therapeutic goal of eradicating all
             known disease with one additional surgery. Portal venous embolization is permitted to
             ensure resectability.

          -  Prior resection of extra-hepatic metastatic disease allowed if completed more than 12
             months previous to study enrollment and now new extra-hepatic disease has been found

          -  Have measurable disease based on RECIST 1.1

          -  Fresh or archived colorectal cancer tissue, preferably from a hepatic metastatic site.
             Archival tissue is acceptable for enrolled into this study. Participants who have no
             archival tissue available do not need to undergo a new biopsy solely for the purpose
             of this study

          -  Participants must have received at least one prior line or chemotherapy including an
             irinotecan or oxaliplatin-fluoropyrimidine-based systemic treatment for colorectal
             cancer

          -  Have performance status of 0 or 1 on the ECOG Performance Scale

          -  Demonstrate an adequate organ function as defined in Table 1. These labs should be
             repeated if not completed within 10 days of SBRT treatment initiation

          -  Female participants of childbearing potential should have a negative urine or serum
             pregnancy test within 10 days of initiating SBRT. If the urine test is positive or
             cannot be confirmed as negative, a serum pregnancy test will be required

          -  Female participants 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). Participants of childbearing potential are those who have
             not been surgically sterilized or have not been free from menses for >1 year

          -  Male participant 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

        Exclusion Criteria:

          -  Current participation and receiving study therapy or previous participation in a study
             of an investigational agent and received study therapy or used an investigational
             device within 4 weeks of the initiation of SBRT

          -  Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 (first
             day of SBRT treatment) or who has not recovered (i.e. < Grade 1 or at baseline) from
             adverse events due to agents administered more than 4 weeks earlier

          -  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. Prior radiotherapy to the
             liver is not allowed

               -  Participants with < Grade 2 neuropathy are an exception to this criterion and may
                  qualify for the study

               -  If the participant received major surgery, they must have recovered adequately
                  from the toxicity and/or complications from the intervention prior to starting
                  therapy

          -  Participant has a diagnosis of immunodeficiency or is receiving systemic steroid
             therapy or any other form of immunosuppressive therapy within 7 days prior to the
             initiation of SBRT

          -  Participant has a known history of active TB (Bacillus Tuberculosis)

          -  Hypersensitivity to pembrolizumab or any of its excipients

          -  Participant has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior
             to study Day 1 (first day or SBRT treatment) or who has not recovered (i.e., ≤ Grade 1
             or at baseline) from adverse events due to agents administered more than 4 weeks
             earlier

          -  Participant 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. Prior
             radiotherapy to the liver is not allowed. (Notes: Participants with ≤ Grade 2
             neuropathy are an exception to this criterion and may qualify for the study. If
             participant received major surgery, they must have recovered adequately from the
             toxicity and/or complications from the intervention prior to starting therapy.)

          -  Participant has a known additional malignancy that is progressing or requires active
             treatment. Exceptions include basal cell carcinoma of the skin or squamous cell
             carcinoma of the skin that has undergone potentially curative therapy or in situ
             cervical cancer.

          -  Participant has known active central nervous system (CNS) metastases and/or
             carcinomatous meningitis. Participants with previously resected brain metastases may
             participate provided it has been at least 6 months and no CNS progression has been
             identified.

          -  Participant has active autoimmune disease that has required systemic treatment in the
             past 2 years (i.e. with use of disease modifying agents, corticosteroids or
             immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic
             corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is
             not considered a form of systemic treatment.

          -  Participant has known history of, or any evidence of active, non-infectious
             pneumonitis.

          -  Participant has an active infection requiring systemic therapy.

          -  Participant has a history or current evidence of any condition, therapy, or laboratory
             abnormality that might confound the results of the trial, interfere with the
             participant's participation for the full duration of the trial, or is not in the best
             interest of the participant to participate, in the opinion of the treating
             investigator.

          -  Participant has known psychiatric or substance abuse disorders that would interfere
             with cooperation with the requirements of the trial.

          -  Participant 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.

          -  Participant has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2
             agent.

          -  Participant has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2
             antibodies).

          -  Participant has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g.,
             HCV RNA [qualitative or quantitative] is detected).

          -  Participant has received a live vaccine within 30 days of planned start of study
             therapy.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recurrence rate at 1 year
Time Frame:1 year
Safety Issue:
Description:Determine the recurrence rate at 1 year following clearance of metastatic disease in the setting of treatment with SBRT and pembrolizumab

Secondary Outcome Measures

Measure:Time to recurrence estimated using the Kaplan-Meier method
Time Frame:1 year
Safety Issue:
Description:The 95% confidence of the median time to recurrence will be calculated using the Brookmeyer-Crowley method
Measure:Disease-free survival estimated using the Kaplan-Meier method
Time Frame:1 year
Safety Issue:
Description:The 95% confidence of the median time to disease free survival calculated using the Brookmeyer-Crowley method.
Measure:Overall survival estimated using the Kaplan-Meier method
Time Frame:1 year
Safety Issue:
Description:The 95% confidence of the median time to overall survival calculated using the Brookmeyer-Crowley method.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Wisconsin, Madison

Last Updated