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

NCT03770689 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: MS100036_00202018-002275-18
• Study Type: interventional
• Target: 19
• Locations: 2 countries
• Sites: 14

Brief Summary

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

Conditions

Locally Advanced Rectal Cancer

Keywords

DNA-PK inhibitor; Peposertib; capecitabine

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Experienced Dose Limiting Toxicity (DLT) Confirmed by Safety Monitoring Committee (SMC)

  DLT is defined as any of following treatment emergent adverse events (TEAEs) considered possibly related to study treatment by Investigator and/or Sponsor up to completion of assigned chemoradiotherapy treatment. DLT were based on SMC: Adverse drug reaction that, in the opinion of SMC, is of potential clinical significance such that further dose escalation would expose participants to unacceptable risk; Any occurrence of drug-induced liver injury meeting the Hy's law criteria; Any Grade 3 toxicity excluding diarrhea, neutropenia lasting for ≤ 5 days, nausea \& vomiting, Grade 3 thrombocytopenia without bleeding; Grade ≥ 4 AEs at least possibly related to study drug, irrespective of duration, excluding: Isolated Grade 4 lymphocytopenia without clinical symptoms; Neutropenia lasting for ≤ 5 days and not associated with fever; Any toxicity related to study drug that causes participant to receive \> 80% of planned peposertib, capecitabine or RT dose.

  Time from first study intervention up to 19 weeks (including 5.5 weeks of treatment and 13.5 weeks of short term safety follow-up period)

Secondary Outcomes (17)

• Number of Participants Wtih Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute Common Terminology Criteria of Adverse Events (NCI-CTCAE) Version 5.0

  Time from first study intervention up to long term safety follow-up period (Up to Month 35)

• Number of Participants With Abnormalities [Grade Greater Than or Equals to (>=) 3] in Laboratory Test Values

  Time from first study intervention up to long term safety follow-up period (Up to Month 35)

• Number of Participants With Markedly Abnormal Vital Sign Measurements

  Time from first study intervention up to long term safety follow-up period (Up to Month 35)

• Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings

  Time from first study intervention up to long term safety follow-up period (Up to Month 35)

• Percentage of Participants With Composite Pathological Complete Response (pCR)/ Clinical Complete Response (cCR)

  At Week 15

Study Arms (4)

Peposertib 50 mg + RT + Capecitabine

EXPERIMENTAL

Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m\^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

Drug: Peposertib 50 mg; Drug: Capecitabine; Radiation: Radiotherapy (RT)

Peposertib 100 mg + RT + Capecitabine

EXPERIMENTAL

Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

Drug: Peposertib 100 mg; Drug: Capecitabine; Radiation: Radiotherapy (RT)

Peposertib 150 mg + RT + Capecitabine

EXPERIMENTAL

Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

Drug: Peposertib 150 mg; Drug: Capecitabine; Radiation: Radiotherapy (RT)

Peposertib 250 mg + RT + Capecitabine

EXPERIMENTAL

Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.

Drug: Peposertib 250 mg; Drug: Capecitabine; Radiation: Radiotherapy (RT)

Interventions

Peposertib 50 mg DRUG

Participants received peposertib 50 milligram (mg) once daily 5 days per week up to 5.5 weeks.

Also known as: M3814, MSC2490484A

Peposertib 50 mg + RT + Capecitabine

Peposertib 100 mg DRUG

Participants received peposertib 100 mg once daily 5 days per week up to 5.5 weeks.

Peposertib 100 mg + RT + Capecitabine

Peposertib 150 mg DRUG

Participants received peposertib 150 mg once daily 5 days per week up to 5.5 weeks.

Peposertib 150 mg + RT + Capecitabine

Peposertib 250 mg DRUG

Participants received peposertib 250 mg once daily 5 days per week up to 5.5 weeks.

Peposertib 250 mg + RT + Capecitabine

Capecitabine DRUG

Participants received capecitabine at a dose of 825 milligram per square meter (mg/m\^2) twice daily 5 days per week up to 5.5 weeks.

Peposertib 100 mg + RT + Capecitabine; Peposertib 150 mg + RT + Capecitabine; Peposertib 250 mg + RT + Capecitabine; Peposertib 50 mg + RT + Capecitabine

Radiotherapy (RT) RADIATION

Participants received RT 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks.

Peposertib 100 mg + RT + Capecitabine; Peposertib 150 mg + RT + Capecitabine; Peposertib 250 mg + RT + Capecitabine; Peposertib 50 mg + RT + Capecitabine

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (14)

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Yale University - Pediatric Respiratory Medicine

New Haven, Connecticut, 06520, United States

Location

Northwell Health, Inc

Great Neck, New York, 10042, United States

Location

Memorial Sloan-Kettering Cancer Center (MSKCC) - New York

New York, New York, 10065, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Ohio State University Clinical Trials Management Office - Ohio State CTMO Parent

Columbus, Ohio, 43210, United States

Location

University of Toledo Medical Center - Hematology/Oncology

Toledo, Ohio, 43614, United States

Location

Med. Univ. of South Carolina

Charleston, South Carolina, 29425, United States

Location

Greenville Hospital System University Medical Center (ITOR)

Greenville, South Carolina, 29605, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Hospital Universitari Vall d'Hebron - Dept of Oncology

Barcelona, Spain

Location

Hospital Universitario 12 de Octubre - Servicio de Oncologia

Madrid, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, Spain

Location

Hospital Clinico Universitario de Valencia - Servicio de Hematologia y Oncologia Medica

Valencia, Spain

Location

Related Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources
• DDRiver website

MeSH Terms

Interventions

peposertib; Capecitabine; Radiotherapy

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

Limitations and Caveats

As decided by sponsor study was discontinued prior to the initiation of the Phase II part of the study; therefore, results only from the Phase Ib part of the study was reported.

Results Point of Contact

• Title: Communication Center
• Organization: Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2018
• First Posted: December 10, 2018
• Study Start: March 20, 2019
• Primary Completion: June 21, 2021
• Study Completion: February 21, 2022
• Last Updated: March 21, 2023
• Results First Posted: July 7, 2022

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (4); US (10)