Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Peposertib in Combination With Capecitabine and RT in Rectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03770689
Recruitment Status : Active, not recruiting
First Posted : December 10, 2018
Last Update Posted : August 31, 2021
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Brief Summary:
The main purpose of the study is to define maximum tolerated dose (MTD), recommended Phase II dose (RP2D) safety and tolerability of Peposertib in combination with capecitabine and radiotherapy (RT).

Condition or disease Intervention/treatment Phase
Locally Advanced Rectal Cancer Drug: Peposertib Drug: Capecitabine Radiation: Radiotherapy (RT) Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter Study With an Open-label Phase Ib Part Followed by a Randomized, Placebo-controlled, Double-blind, Phase II Part to Evaluate Efficacy, Safety, Tolerability, and Pharmacokinetics of the DNA-PK Inhibitor Peposertib (M3814) in Combination With Capecitabine and RT in Participants With Locally Advanced Rectal Cancer
Actual Study Start Date : March 20, 2019
Actual Primary Completion Date : June 21, 2021
Estimated Study Completion Date : February 17, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Peposertib + Capecitabine + RT Drug: Peposertib
Participants will receive peposertib at an escalated dose starting from 50 mg once daily 5 days per week in first cohort up to week 6 and for the next cohorts peposertib dose will be determined by the Safety Monitoring Committee (SMC) guided by a Bayesian 2-parameter logistic regression model with overdose control.
Other Names:
  • M3814
  • MSC2490484A

Drug: Capecitabine
Participants will receive capecitabine at a dose of 825 milligram per square meter (mg/m^2) twice daily 5 days per week.

Radiation: Radiotherapy (RT)
Participants will receive RT 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions (corresponding to 5 to 5.5 weeks).




Primary Outcome Measures :
  1. Number of Participants Experiencing a Dose Limiting Toxicity (DLT) [ Time Frame: Time from first dose of study drug to end of chemo radiotherapy with a final assessment at 4 weeks post-surgery ]

Secondary Outcome Measures :
  1. Occurrence of Treatment-related Adverse Events (TEAEs) According to National Cancer Institute Common Terminology Criteria of Adverse Events (NCI-CTCAE) version 5.0 [ Time Frame: Time from first dose of study drug to final assessment at 1 year ]
  2. Number of Participants With Abnormalities (Grade Greater than or equals to (>=) 3) in Laboratory Test Values [ Time Frame: Time from first study drug to final assessment at 1 year ]
  3. Number of Participants With Markedly Abnormal Vital Sign Measurements [ Time Frame: Time from first dose of study drug to final assessment at 1 year ]
  4. Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Findings [ Time Frame: Time from first dose of study drug to final assessment at 1 year ]
  5. Proportion of Participants With Pathological Complete Response (pCR) and Clinical Complete Response (cCR) [ Time Frame: Pathology evaluation of specimen after surgery (pCR) and clinical evaluation 1 to 2 weeks prior to surgery (cCR) ]
  6. Disease-free Survival [ Time Frame: Time from first study drug to final assessment at 1 year ]
  7. Proportion of Participants With Pathological Complete Response (pCR) [ Time Frame: Evaluation of specimen after surgery ]
  8. Proportion of Participants With Clinical Complete Response (cCR) [ Time Frame: Time from first study drug until 1 to 2 weeks prior to surgery ]
  9. Time from Surgery to Local Recurrence and Distant Metastasis [ Time Frame: Time from surgery to final assessment at 1 year ]
  10. Neoadjuvant Rectal Score [ Time Frame: Pathology evaluation of specimen after surgery ]
  11. Maximum Observed Drug Concentration (Cmax) of Peposertib [ Time Frame: Pre-dose, 1, 2, 3 and 4 hour post-dose on Fraction Day (FD1) and Fraction Day 9 ]
  12. Area Under the Plasma Concentration-time Curve From Time Zero to Last Sampling Time (tlast) (AUC0-t) of Peposertib [ Time Frame: Pre-dose, 1, 2, 3 and 4 hour post-dose on Fraction Day 1 and Fraction Day 9 ]
  13. Time to Reach Maximum Plasma Concentration (tmax) of Peposertib [ Time Frame: Pre-dose, 1, 2, 3 and 4 hour post-dose on Fraction Day 1 and Fraction Day 9 ]
  14. Total Body Clearance of Drug From Plasma Following Oral Administration (CL/f) of Peposertib [ Time Frame: Pre-dose, 1, 2, 3 and 4 hour post-dose on Fraction Day 1 and Fraction Day 9 ]
  15. Apparent Volume of Distribution (Vz/f) of Peposertib [ Time Frame: Pre-dose, 1, 2, 3 and 4 hour post-dose on Fraction Day 1 and Fraction Day 9 ]
  16. Apparent Terminal Half-life (t1/2) of Peposertib [ Time Frame: Pre-dose, 1, 2, 3 and 4 hour post-dose on Fraction Day 1 and Fraction Day 9 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Participants who have an Eastern Cooperative Oncology Group Performance Status less than or equals to (<=) 1
  • Participants who have histologically confirmed and localized resectable rectal cancer (Stage 3)
  • Participants who received induction chemotherapy are allowed to be enrolled to this study except this induction is resulting in clinical complete response (cCR) or tumor progression
  • Participants who have lower edge of the tumor located in rectum
  • Adequate hematological, hepatic and renal function as defined in the protocol
  • Male participants if they agree to the following during the study intervention period and for at least 12 weeks after the last dose of study intervention
  • Female participants are eligible if not pregnant or breastfeeding
  • Other protocol defined inclusion criteria could apply

Exclusion Criteria:

  • Participants with history of any other significant medical disease or psychiatric conditions that might in the assessment of the Investigator preclude safe participation in the study
  • Participants with history of difficulty swallowing, malabsorption, or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the study intervention
  • Unstable cardiovascular function within 6 months prior to enrollment
  • Hypertension uncontrolled by medication (ie, systolic blood pressure >= 150 millimeter of mercury (mmHg) and diastolic blood pressure >= 90 mmHg)
  • Participants with history of other malignant disease within the past 5 years, other than successfully treated basal carcinoma of the skin or carcinoma in situ of the cervix
  • Participants with known human immunodeficiency virus positivity, known active hepatitis (for example, hepatitis B virus or hepatitis C virus), current alcohol abuse, or cirrhosis
  • Participants with ongoing active infection or treatment with a live attenuated vaccine within 4 weeks of dosing
  • Participants with concomitant use of H2-blocker or proton pump inhibitors (PPIs) (or unable to stop at least 5 days prior to the first treatment). Note that calcium carbonate is acceptable
  • Participation in any interventional clinical study within 28 days prior to Screening or during participation in this study
  • Other protocol defined exclusion criteria could apply.

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): NCT03770689


Locations
Layout table for location information
United States, Colorado
University of Colorado Cancer Center
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University - Pediatric Respiratory Medicine
New Haven, Connecticut, United States, 06520
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10461
Northwell Health, Inc
Great Neck, New York, United States, 10042
Memorial Sloan-Kettering Cancer Center (MSKCC) - New York
New York, New York, United States, 10065
United States, Ohio
Ohio State University Clinical Trials Management Office - Ohio State CTMO Parent
Columbus, Ohio, United States, 43210
University of Toledo Medical Center - Hematology/Oncology
Toledo, Ohio, United States, 43614
United States, South Carolina
Med. Univ. of South Carolina
Charleston, South Carolina, United States, 29425
Greenville Hospital System University Medical Center (ITOR)
Greenville, South Carolina, United States, 29605
United States, Texas
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Spain
Hospital Universitari Vall d'Hebron - Dept of Oncology
Barcelona, Spain
Hospital Universitario 12 de Octubre - Servicio de Oncologia
Madrid, Spain
Hospital Regional Universitario de Malaga
Málaga, Spain
Hospital Clinico Universitario de Valencia - Servicio de Hematologia y Oncologia Medica
Valencia, Spain
Sponsors and Collaborators
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany
Investigators
Layout table for investigator information
Study Director: Medical Responsible Merck KGaA, Darmstadt, Germany
Additional Information:
Layout table for additonal information
Responsible Party: EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier: NCT03770689    
Other Study ID Numbers: MS100036_0020
2018-002275-18 ( EudraCT Number )
First Posted: December 10, 2018    Key Record Dates
Last Update Posted: August 31, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: EMD Serono, Inc. is committed to sharing patient-level data and supporting documentation from applicable studies according to company policies. Further information on data sharing and how to request data can be found on our website https://www.emdgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):
DNA-PK inhibitor
Peposertib
capecitabine
Additional relevant MeSH terms:
Layout table for MeSH terms
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Capecitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents