Back to resultsStudy of Peposertib in Combination With Capecitabine and RT in Rectal Cancer
Primary Purpose
Locally Advanced Rectal Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Peposertib 50 mg
Peposertib 100 mg
Peposertib 150 mg
Peposertib 250 mg
Capecitabine
Radiotherapy (RT)
Sponsored by
About this trial
This is an interventional treatment trial for Locally Advanced Rectal Cancer focused on measuring DNA-PK inhibitor, Peposertib, capecitabine
Eligibility 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.
Sites / Locations
- University of Colorado Cancer Center
- Yale University - Pediatric Respiratory Medicine
- Montefiore Medical Center
- Northwell Health, Inc
- Memorial Sloan-Kettering Cancer Center (MSKCC) - New York
- Ohio State University Clinical Trials Management Office - Ohio State CTMO Parent
- University of Toledo Medical Center - Hematology/Oncology
- Med. Univ. of South Carolina
- Greenville Hospital System University Medical Center (ITOR)
- The University of Texas MD Anderson Cancer Center
- Hospital Universitari Vall d'Hebron - Dept of Oncology
- Hospital Universitario 12 de Octubre - Servicio de Oncologia
- Hospital Regional Universitario de Malaga
- Hospital Clinico Universitario de Valencia - Servicio de Hematologia y Oncologia Medica
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Peposertib 50 mg + RT + Capecitabine
Peposertib 100 mg + RT + Capecitabine
Peposertib 150 mg + RT + Capecitabine
Peposertib 250 mg + RT + Capecitabine
Arm Description
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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
Adverse event (AE) is any untoward medical occurrence in participant administered pharmaceutical product, regardless of causal relationship with this treatment. Therefore, an AE can be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless if it is considered related to medicinal product. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to study intervention. Number of participants with TEAEs and treatment related TEAEs were reported.
Number of Participants With Abnormalities [Grade Greater Than or Equals to (>=) 3] in Laboratory Test Values
The laboratory measurements included hematology and biochemistry values were graded with National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 toxicity grades (where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening and Grade 5 = death). Number of participants with abnormalities Grade >= 3 in laboratory test values were reported.
Number of Participants With Markedly Abnormal Vital Sign Measurements
Vital sign assessments included assessments of heart rate, diastolic blood pressure, systolic blood pressure, respiratory rate and temperature. Number of participants with markedly abnormal vital sign measurements were reported.
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings
Electrocardiograms (ECG) was obtained after the participant has been in a semi-supine position for at least 5 min. ECG parameters included heart rate, PQ/PR duration, QRS and QT duration, QT Interval. Clinical significance was determined by the investigator. Number of participants with clinically significant abnormalities in 12-lead ECG were reported.
Percentage of Participants With Composite Pathological Complete Response (pCR)/ Clinical Complete Response (cCR)
pCR: It is defined as absence of viable tumor cells in the primary tumor and lymph nodes. Participants considered to have a pCR if they undergo surgery and no residual cancer is found on histological examination of removed specimen. cCR: Participants are considered to have a cCR if: 1) Absence of any residual tumor in primary site and draining lymph nodes on imaging with magnetic resonance imaging; 2) No visible lesion at endoscopy except a flat scar, telangiectasia, and/or whitening of mucosa; 3) Absence of any palpable tumor or irregularity on digital rectal examination (DRE) and endoscopic ultrasonography (EUS); 4) If a biopsy is taken, it must be negative. Participants are considered as responders to composite endpoint pCR/cCR if participant had surgery and had pCR; participant did not undergo surgery but had cCR. Number of participants with composite pathological complete response (pCR)/ clinical complete response (cCR) were reported.
Disease-free Survival
Disease-free Survival time, defined as the time from first treatment day to the date of the first documentation of objective progressive disease or death due to any cause, whichever occurs first. Median disease-free survival time was estimated according to Kaplan-Meier method.
Percentage of Participants With Pathological Complete Response (pCR)
pCR is defined as the absence of viable tumor cells in the primary tumor and lymph nodes. Participants are considered to have a pCR if they undergo surgery and no residual cancer is found on histological examination of the removed specimen.
Percentage of Participants With Clinical Complete Response (cCR)
cCR: It is defined as participants considered to have a cCR if: 1) Absence of any residual tumor in the primary site and draining lymph nodes on imaging with magnetic resonance; 2) No visible lesion at endoscopy except a flat scar, telangiectasia, and/or whitening of the mucosa; 3) Absence of any palpable tumor or irregularity on digital rectal examination (DRE) and endoscopic ultrasonography (EUS); 4) If a biopsy is taken, it must be negative.
Time From Surgery to Local Recurrence
Time from surgery to local recurrence defined as time from day of surgery to the date of the first documentation of progression of disease, flagged as local recurrence. Median time from surgery to local recurrence was estimated according to Kaplan-Meier method.
Time From Surgery to Distant Metastasis
Time from surgery to distant metastasis defined as time from day of surgery to the date of the first documentation of progression of disease, flagged as distant metastasis. Median time from surgery to distant metastasis was estimated according to Kaplan-Meier method.
Neoadjuvant Rectal (NAR) Score
The NAR formula includes the clinical tumor (cT) stage, pathologic tumor (pT), and node (pN) stage according to the tumor, node, metastasis classification system for colorectal cancers. The NAR formula is as follows:
[5pN- 3 (cT- pT) + 12]2 / 9.61
NAR score ranges from 0 to 100, whereas a score close to 100 is indicative of a poorer prognosis.
Maximum Observed Plasma Concentration (Cmax) of Peposertib
Cmax was obtained directly from the concentration versus time curve. One participant was assigned to receive peposertib 100 mg; however, this participant took peposertib 50 mg for FD 1 through FD 10 and then took peposertib 100 mg for remainder of study participation. PK results for this participant was summarized by actual dose received (50 mg) whereas non-PK results are summarized by planned dose (100 mg).
Area Under the Plasma Concentration-time Curve From Time Zero to Last Sampling Time (Tlast) (AUC0-t) of Peposertib
Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.
Time to Reach Maximum Plasma Concentration (Tmax) of Peposertib
Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Total Body Clearance Following Oral Administration (CL/f) of Peposertib
The apparent total body clearance of study intervention following extravascular administration on FD1, taking into account the fraction of dose absorbed. CL/f = Dose oral (p.o.)/AUC0-inf. The predicted AUC0-inf should be used.
Apparent Volume of Distribution (Vz/f) of Peposertib
The apparent volume of distribution during the terminal phase following extravascular administration, based on the fraction of dose absorbed. Vz/f = Dose/(AUC0-inf multiplied by Lambda z) following single dose. Vz/f= Dose/(AUCtau*Lambda z) following multiple dose. One participant was assigned to receive peposertib 100 mg; however, this participant took peposertib 50 mg for FD 1 through FD 10 and then took peposertib 100 mg for remainder of study participation. PK results for this participant was summarized by actual dose received (50 mg) whereas non-PK results are summarized by planned dose (100 mg).
Apparent Terminal Half-life (t1/2) of Peposertib
Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z. One participant was assigned to receive peposertib 100 mg; however, this participant took peposertib 50 mg for FD 1 through FD 10 and then took peposertib 100 mg for remainder of study participation. PK results for this participant was summarized by actual dose received (50 mg) whereas non-PK results are summarized by planned dose (100 mg).
Full Information
NCT ID
NCT03770689
First Posted
December 7, 2018
Last Updated
March 20, 2023
Sponsor
EMD Serono Research & Development Institute, Inc.
Collaborators
Merck KGaA, Darmstadt, Germany
1. Study Identification
Unique Protocol Identification Number
NCT03770689
Brief Title
Study of Peposertib in Combination With Capecitabine and RT in Rectal Cancer
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
March 20, 2019 (Actual)
Primary Completion Date
June 21, 2021 (Actual)
Study Completion Date
February 21, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
EMD Serono Research & Development Institute, Inc.
Collaborators
Merck KGaA, Darmstadt, Germany
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced Rectal Cancer
Keywords
DNA-PK inhibitor, Peposertib, capecitabine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Peposertib 50 mg + RT + Capecitabine
Arm Type
Experimental
Arm Description
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.
Arm Title
Peposertib 100 mg + RT + Capecitabine
Arm Type
Experimental
Arm Description
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.
Arm Title
Peposertib 150 mg + RT + Capecitabine
Arm Type
Experimental
Arm Description
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.
Arm Title
Peposertib 250 mg + RT + Capecitabine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Peposertib 50 mg
Other Intervention Name(s)
M3814, MSC2490484A
Intervention Description
Participants received peposertib 50 milligram (mg) once daily 5 days per week up to 5.5 weeks.
Intervention Type
Drug
Intervention Name(s)
Peposertib 100 mg
Intervention Description
Participants received peposertib 100 mg once daily 5 days per week up to 5.5 weeks.
Intervention Type
Drug
Intervention Name(s)
Peposertib 150 mg
Intervention Description
Participants received peposertib 150 mg once daily 5 days per week up to 5.5 weeks.
Intervention Type
Drug
Intervention Name(s)
Peposertib 250 mg
Intervention Description
Participants received peposertib 250 mg once daily 5 days per week up to 5.5 weeks.
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
Radiotherapy (RT)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants Who Experienced Dose Limiting Toxicity (DLT) Confirmed by Safety Monitoring Committee (SMC)
Description
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 Frame
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 Outcome Measure Information:
Title
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
Description
Adverse event (AE) is any untoward medical occurrence in participant administered pharmaceutical product, regardless of causal relationship with this treatment. Therefore, an AE can be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless if it is considered related to medicinal product. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to study intervention. Number of participants with TEAEs and treatment related TEAEs were reported.
Time Frame
Time from first study intervention up to long term safety follow-up period (Up to Month 35)
Title
Number of Participants With Abnormalities [Grade Greater Than or Equals to (>=) 3] in Laboratory Test Values
Description
The laboratory measurements included hematology and biochemistry values were graded with National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 toxicity grades (where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening and Grade 5 = death). Number of participants with abnormalities Grade >= 3 in laboratory test values were reported.
Time Frame
Time from first study intervention up to long term safety follow-up period (Up to Month 35)
Title
Number of Participants With Markedly Abnormal Vital Sign Measurements
Description
Vital sign assessments included assessments of heart rate, diastolic blood pressure, systolic blood pressure, respiratory rate and temperature. Number of participants with markedly abnormal vital sign measurements were reported.
Time Frame
Time from first study intervention up to long term safety follow-up period (Up to Month 35)
Title
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings
Description
Electrocardiograms (ECG) was obtained after the participant has been in a semi-supine position for at least 5 min. ECG parameters included heart rate, PQ/PR duration, QRS and QT duration, QT Interval. Clinical significance was determined by the investigator. Number of participants with clinically significant abnormalities in 12-lead ECG were reported.
Time Frame
Time from first study intervention up to long term safety follow-up period (Up to Month 35)
Title
Percentage of Participants With Composite Pathological Complete Response (pCR)/ Clinical Complete Response (cCR)
Description
pCR: It is defined as absence of viable tumor cells in the primary tumor and lymph nodes. Participants considered to have a pCR if they undergo surgery and no residual cancer is found on histological examination of removed specimen. cCR: Participants are considered to have a cCR if: 1) Absence of any residual tumor in primary site and draining lymph nodes on imaging with magnetic resonance imaging; 2) No visible lesion at endoscopy except a flat scar, telangiectasia, and/or whitening of mucosa; 3) Absence of any palpable tumor or irregularity on digital rectal examination (DRE) and endoscopic ultrasonography (EUS); 4) If a biopsy is taken, it must be negative. Participants are considered as responders to composite endpoint pCR/cCR if participant had surgery and had pCR; participant did not undergo surgery but had cCR. Number of participants with composite pathological complete response (pCR)/ clinical complete response (cCR) were reported.
Time Frame
At Week 15
Title
Disease-free Survival
Description
Disease-free Survival time, defined as the time from first treatment day to the date of the first documentation of objective progressive disease or death due to any cause, whichever occurs first. Median disease-free survival time was estimated according to Kaplan-Meier method.
Time Frame
Time from first study intervention up to approximately 35 months
Title
Percentage of Participants With Pathological Complete Response (pCR)
Description
pCR is defined as the absence of viable tumor cells in the primary tumor and lymph nodes. Participants are considered to have a pCR if they undergo surgery and no residual cancer is found on histological examination of the removed specimen.
Time Frame
At Week 15
Title
Percentage of Participants With Clinical Complete Response (cCR)
Description
cCR: It is defined as participants considered to have a cCR if: 1) Absence of any residual tumor in the primary site and draining lymph nodes on imaging with magnetic resonance; 2) No visible lesion at endoscopy except a flat scar, telangiectasia, and/or whitening of the mucosa; 3) Absence of any palpable tumor or irregularity on digital rectal examination (DRE) and endoscopic ultrasonography (EUS); 4) If a biopsy is taken, it must be negative.
Time Frame
At Week 15
Title
Time From Surgery to Local Recurrence
Description
Time from surgery to local recurrence defined as time from day of surgery to the date of the first documentation of progression of disease, flagged as local recurrence. Median time from surgery to local recurrence was estimated according to Kaplan-Meier method.
Time Frame
Time from surgery up to 15 months
Title
Time From Surgery to Distant Metastasis
Description
Time from surgery to distant metastasis defined as time from day of surgery to the date of the first documentation of progression of disease, flagged as distant metastasis. Median time from surgery to distant metastasis was estimated according to Kaplan-Meier method.
Time Frame
Time from surgery up to 15 months
Title
Neoadjuvant Rectal (NAR) Score
Description
The NAR formula includes the clinical tumor (cT) stage, pathologic tumor (pT), and node (pN) stage according to the tumor, node, metastasis classification system for colorectal cancers. The NAR formula is as follows:
[5pN- 3 (cT- pT) + 12]2 / 9.61
NAR score ranges from 0 to 100, whereas a score close to 100 is indicative of a poorer prognosis.
Time Frame
At Week 15
Title
Maximum Observed Plasma Concentration (Cmax) of Peposertib
Description
Cmax was obtained directly from the concentration versus time curve. One participant was assigned to receive peposertib 100 mg; however, this participant took peposertib 50 mg for FD 1 through FD 10 and then took peposertib 100 mg for remainder of study participation. PK results for this participant was summarized by actual dose received (50 mg) whereas non-PK results are summarized by planned dose (100 mg).
Time Frame
Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Fraction Day 1 and Fraction Day 9
Title
Area Under the Plasma Concentration-time Curve From Time Zero to Last Sampling Time (Tlast) (AUC0-t) of Peposertib
Description
Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.
Time Frame
Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1 and Fraction Day 9
Title
Time to Reach Maximum Plasma Concentration (Tmax) of Peposertib
Description
Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Time Frame
Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1 and Fraction Day 9
Title
Total Body Clearance Following Oral Administration (CL/f) of Peposertib
Description
The apparent total body clearance of study intervention following extravascular administration on FD1, taking into account the fraction of dose absorbed. CL/f = Dose oral (p.o.)/AUC0-inf. The predicted AUC0-inf should be used.
Time Frame
Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1
Title
Apparent Volume of Distribution (Vz/f) of Peposertib
Description
The apparent volume of distribution during the terminal phase following extravascular administration, based on the fraction of dose absorbed. Vz/f = Dose/(AUC0-inf multiplied by Lambda z) following single dose. Vz/f= Dose/(AUCtau*Lambda z) following multiple dose. One participant was assigned to receive peposertib 100 mg; however, this participant took peposertib 50 mg for FD 1 through FD 10 and then took peposertib 100 mg for remainder of study participation. PK results for this participant was summarized by actual dose received (50 mg) whereas non-PK results are summarized by planned dose (100 mg).
Time Frame
Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1 and Fraction Day 9
Title
Apparent Terminal Half-life (t1/2) of Peposertib
Description
Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z. One participant was assigned to receive peposertib 100 mg; however, this participant took peposertib 50 mg for FD 1 through FD 10 and then took peposertib 100 mg for remainder of study participation. PK results for this participant was summarized by actual dose received (50 mg) whereas non-PK results are summarized by planned dose (100 mg).
Time Frame
Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1 and Fraction Day 9
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
University of Colorado Cancer Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Yale University - Pediatric Respiratory Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Northwell Health, Inc
City
Great Neck
State/Province
New York
ZIP/Postal Code
10042
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center (MSKCC) - New York
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Ohio State University Clinical Trials Management Office - Ohio State CTMO Parent
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
University of Toledo Medical Center - Hematology/Oncology
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43614
Country
United States
Facility Name
Med. Univ. of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Greenville Hospital System University Medical Center (ITOR)
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Hospital Universitari Vall d'Hebron - Dept of Oncology
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre - Servicio de Oncologia
City
Madrid
Country
Spain
Facility Name
Hospital Regional Universitario de Malaga
City
Málaga
Country
Spain
Facility Name
Hospital Clinico Universitario de Valencia - Servicio de Hematologia y Oncologia Medica
City
Valencia
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
Links:
URL
https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS100036_0020
Description
Trial Awareness and Transparency website
URL
https://medical.emdserono.com/en_US/home.html
Description
US Medical Information website, Medical Resources
URL
http://www.DDRiver-trials.com
Description
DDRiver website
Learn more about this trial
Study of Peposertib in Combination With Capecitabine and RT in Rectal Cancer
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