Trial of Chemoradiation and Pembrolizumab in Patients With Rectal Cancer

NCT02586610 | Withdrawn Phase 2 DMC

• 1 other identifier: HCRN GI15-213
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a phase II, prospective open label multi-center study in which subjects with stage II-III rectal cancer will be accrued in order to determine the pathological complete response rate of neoadjuvant pembrolizumab in combination with chemoradiation treatment (CRT). Subjects must have a diagnosis of rectal cancer, stage II (T3-4, N0) or stage III (any T, N1-2). Subjects must have received no prior treatments (chemotherapy, pelvic radiation or surgery) for their rectal cancer. Eligible subjects will receive standard chemoradiation with pembrolizumab administered every 3 weeks on days 1, 22, and 43 of the neoadjuvant interval. In all subjects, restaging endorectal or pelvic MRI with chest and abdominal CT will be performed at 6-8 weeks after completion of neoadjuvant treatment to determine resectability and to rule out any evidence of metastases. Subjects who have resectable disease will undergo surgery within 2-4 weeks of imaging; 8-12 weeks after completion of chemoradiation. Subjects who are found to have unresectable or metastatic disease post treatment with the combination of CRT+ pembrolizumab should receive standard of care definitive treatment per the discretion of their treating physician.

Conditions

Rectal Cancer; Rectal Neoplasm

Keywords

Pembrolizumab; Chemoradiation; Anti-PD-1 Antibody; MK-3475

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR) Rate

  Proportion of subjects with pathological complete response (pCR) as demonstrated by the absence of residual invasive cancer on evaluation of the complete resected rectal specimen.

  Time from start of neoadjuvant chemoradiation until surgical resection (estimate up to 12 weeks after completion of chemoradiation)

Secondary Outcomes (4)

• Density of CD8(+) Tumor-Infiltrating Lymphocytes (TIL)

  Time from baseline until completion of post-neoadjuvant treatment (estimate up to 8 weeks after completion of chemoradiation)

• Response Rate (RR)

  Time from registration to documented progression or subject death from any cause, assessed up to 42 months

• Disease Free Survival (DFS)

  Time from start of protocol treatment to the date of progression or death from any cause, whichever occurs first, assessed up to 42 months

• Overall Survival (OS)

  Time from start of protocol treatment to death from any cause, assessed up to 42 months

Study Arms (1)

Neoadjuvant Treatment

EXPERIMENTAL

All subjects will receive concurrent chemoradiation and pembrolizumab neoadjuvant treatment for 6 weeks: * Pembrolizumab 200 mg IV Days 1, 22 and 43 * Capecitabine 825 mg/m2 PO in twice daily doses (total 1650 mg/m2) on 5 consecutive days / week M-F given on the radiation days for 28 days * Radiation therapy 50.4 GY. Daily fractions of 1.8 Gy over a 6 week interval, excludes weekends

Drug: Pembrolizumab; Drug: Capecitabine; Radiation: Radiation Therapy

Interventions

Pembrolizumab DRUG

Pembrolizumab 200 mg IV Days 1, 22 and 43

Also known as: MK-3475

Neoadjuvant Treatment

Capecitabine DRUG

Capecitabine 825 mg/m2 PO twice a day (daily total 1650 mg/m2) on 5 consecutive days / week M-F given on the radiation days for 28 days

Also known as: Xeloda

Neoadjuvant Treatment

Radiation Therapy RADIATION

Radiation 50.4 GY in daily fractions of 1.8 Gy over a 6 week interval (excludes weekends)

Also known as: XRT

Neoadjuvant Treatment

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 for the trial.
• Be 18 years of age or older on day of signing informed consent.
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1).
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion.
• Have a performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study treatment. 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 treatment. 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 treatment.

You may not qualify if:

• Unresectable disease, as evidenced by invading adjacent organs and surgical resection will not achieve negative margins
• Recurrent rectal cancer
• Evidence of metastatic disease (as determined by chest and abdominal CT).
• Prior malignancy within the prior 5 years. 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.
• Prior radiation for other diagnoses to the expected rectal cancer treatment fields.
• Prior surgery, radiation, chemotherapy, targeted therapy, or investigational therapy for rectal cancer. NOTE: If subject received major surgery for reason other than rectal cancer, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
• Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the planned start of study treatment.
• Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
• Administration of live vaccine within 30 days of planned start of study therapy. Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
• Known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• 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.
• Known history of, or any evidence of active, non-infectious pneumonitis.

Sponsors & Collaborators

• Osama Rahma, MD: lead
• Hoosier Cancer Research Network: collaborator
• Merck Sharp & Dohme LLC: collaborator

Related Links

• Hoosier Cancer Research Network Website

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

pembrolizumab; Capecitabine; Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Therapeutics

Study Officials

• Osama Rahma

  Hoosier Cancer Research Network

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: October 22, 2015
• First Posted: October 26, 2015
• Study Start: October 1, 2016
• Primary Completion: June 1, 2018
• Study Completion: December 1, 2020
• Last Updated: January 20, 2017

Record last verified: 2017-01