Colorectal Cancer, Tumor
Conditions
Keywords
Phase 2a: Multiple solid tumor types, Phase 2b: Second-Line Colorectal Cancer (CRC)
Brief summary
Study 07-PIR-02 is a Phase 2 study designed to evaluate the safety and efficacy of NKTR-102 (PEG-irinotecan) for the treatment of patients with colorectal cancer (CRC). The study is comprised of two sequential components - Phase 2a and Phase 2b. The Phase 2a portion is an open-label, dose-finding trial in multiple solid tumor types that are refractory to standard curative or palliative therapies. The primary endpoint of the Phase 2a is to establish the /recommended Phase 2 Dose (RPTD) of NKTR-102 by measuring the frequency of Dose Limiting Toxicity (DLT). The Phase 2b portion is an open-label, randomized, two-arm study in patients with second-line metastatic colorectal cancer and study participants will be randomized (1:1) to receive either NKTR-102 and cetuximab or irinotecan and cetuximab. The primary endpoint of the Phase 2b portion of the trial is progression-free survival. Secondary endpoints for both the Phase 2a and 2b portion include response rate, response duration, overall survival, standard pharmacokinetics, and incidence of toxicities, including diarrhea and neutropenia.
Detailed description
The Phase 2a portion of this study is completed. The following entries reflect the Phase 2a portion of this study only. The Phase 2b portion of the study was not enrolled. Based on emerging data regarding the corresponding low efficacy of cetuximab in patients with KRAS mutations, as well as revised NKTR-102 clinical development plans, the Phase 2b portion of the study was not completed.
Interventions
DRUGNKTR-102 100 mg/m2
NKTR-102 100 mg/m2 + Cetuximab Arm: All patients received NKTR-102 in combination with cetuximab. NKTR-102 was administered intravenously (IV) once every 3 weeks (q3w) over 90 minutes on Day 1. Patients were to be enrolled in one of the following sequential dosing cohorts of NKTR-102: 100, 125, 150, or 175 mg/m2. Only the 100 and 125 mg/m2 were enrolled.
DRUGNKTR-102 125 mg/m2
NKTR-102 125 mg/m2 + Cetuximab Arm: All patients received NKTR-102 in combination with cetuximab. NKTR-102 was administered intravenously (IV) once every 3 weeks (q3w) over 90 minutes on Day 1. Patients were to be enrolled in one of the following sequential dosing cohorts of NKTR-102: 100, 125, 150, or 175 mg/m2. Only the 100 and 125 mg/m2 were enrolled.
DRUGCetuximab
Cetuximab was administered once weekly via a 2-hour IV infusion at a starting dose of 400 mg/m2 on Day 1 and subsequently administered weekly at 250 mg/m2 via a 1-hour infusion thereafter.
Sponsors
Nektar Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and non-pregnant, non-lactating female patients with an ECOG performance score \<3 who have any type of solid tumor refractory to standard therapy and who have adequate bone marrow and organ function at screening.
Exclusion criteria
* Patients must not have used any CYP3A4 inducers or inhibitors with 2 weeks prior to the first day of study drug treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Dose Limiting Toxicities | 12 months | Number of patients with Dose Limiting Toxicities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Dose Limiting Toxicities by NCI-CTCAE | 12 months | Number of patients with Dose Limiting Toxicities by NCI-CTCAE |
| Number of Patients With Overall Response | 12 months | Complete Response is defined as the disappearance of all target lesions. Partial Response is defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. The best overall response was the best response recorded from the start of the study drug until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NKTR-102 100 mg/m2 + Cetuximab All patients received NKTR-102 in combination with cetuximab. NKTR-102 was administered intravenously (IV) once every 3 weeks (q3w) over 90 minutes on Day 1. Patients were to be enrolled in one of the following sequential dosing cohorts of NKTR-102: 100, 125, 150, or 175 mg/m2. Only the 100 and 125 mg/m2 were enrolled. | 12 |
| NKTR-102 125 mg/m2 + Cetuximab All patients received NKTR-102 in combination with cetuximab. NKTR-102 was administered intravenously (IV) once every 3 weeks (q3w) over 90 minutes on Day 1. Patients were to be enrolled in one of the following sequential dosing cohorts of NKTR-102: 100, 125, 150, or 175 mg/m2. Only the 100 and 125 mg/m2 were enrolled. | 6 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Brain metastases | 1 | 0 |
| Overall Study | Disease progression | 8 | 3 |
| Overall Study | Tx delayed >2 wks, hospitalized for AE | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
| Overall Study | Withdrawal of consent | 0 | 1 |
Baseline characteristics
| Characteristic | Total | NKTR-102 125 mg/m2 + Cetuximab | NKTR-102 100 mg/m2 + Cetuximab |
|---|---|---|---|
| Age, Continuous | 64.0 years | 65.5 years | 52.0 years |
| Copies of UGT1A1*28 Not detected | 8 Participants | 1 Participants | 7 Participants |
| Copies of UGT1A1*28 One Copy (Heterozygous) | 9 Participants | 4 Participants | 5 Participants |
| Copies of UGT1A1*28 Two Copies (Homozygous) | 1 Participants | 1 Participants | 0 Participants |
| ECOG Performance 0 | 4 Participants | 0 Participants | 4 Participants |
| ECOG Performance 1 | 14 Participants | 6 Participants | 8 Participants |
| ECOG Performance 2 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Female | 9 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Male | 9 Participants | 2 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 12 | 0 / 6 | 1 / 18 |
| other Total, other adverse events | 12 / 12 | 6 / 6 | 18 / 18 |
| serious Total, serious adverse events | 5 / 12 | 3 / 6 | 8 / 18 |
Outcome results
Primary
Number of Patients With Dose Limiting Toxicities
Number of patients with Dose Limiting Toxicities
Time frame: 12 months
Population: ITT/Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NKTR-102 100 mg/m2 + Cetuximab | Number of Patients With Dose Limiting Toxicities | Diarrhoea | 1 Participants |
| NKTR-102 100 mg/m2 + Cetuximab | Number of Patients With Dose Limiting Toxicities | Dehydration | 0 Participants |
| NKTR-102 100 mg/m2 + Cetuximab | Number of Patients With Dose Limiting Toxicities | Renal Failure Acute | 0 Participants |
| NKTR-102 125 mg/m2 + Cetuximab | Number of Patients With Dose Limiting Toxicities | Diarrhoea | 1 Participants |
| NKTR-102 125 mg/m2 + Cetuximab | Number of Patients With Dose Limiting Toxicities | Dehydration | 1 Participants |
| NKTR-102 125 mg/m2 + Cetuximab | Number of Patients With Dose Limiting Toxicities | Renal Failure Acute | 1 Participants |
| Total | Number of Patients With Dose Limiting Toxicities | Dehydration | 1 Participants |
| Total | Number of Patients With Dose Limiting Toxicities | Renal Failure Acute | 1 Participants |
| Total | Number of Patients With Dose Limiting Toxicities | Diarrhoea | 2 Participants |
Secondary
Number of Patients With Dose Limiting Toxicities by NCI-CTCAE
Number of patients with Dose Limiting Toxicities by NCI-CTCAE
Time frame: 12 months
Population: ITT/Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NKTR-102 100 mg/m2 + Cetuximab | Number of Patients With Dose Limiting Toxicities by NCI-CTCAE | Dehydration : Any grade | 0 Participants |
| NKTR-102 100 mg/m2 + Cetuximab | Number of Patients With Dose Limiting Toxicities by NCI-CTCAE | Dehydration : Grade 3 | 0 Participants |
| NKTR-102 100 mg/m2 + Cetuximab | Number of Patients With Dose Limiting Toxicities by NCI-CTCAE | Diarrhoea : Any grade | 1 Participants |
| NKTR-102 100 mg/m2 + Cetuximab | Number of Patients With Dose Limiting Toxicities by NCI-CTCAE | Diarrhoea : Grade 3 | 1 Participants |
| NKTR-102 100 mg/m2 + Cetuximab | Number of Patients With Dose Limiting Toxicities by NCI-CTCAE | Renal Failure Acute : Any grade | 0 Participants |
| NKTR-102 100 mg/m2 + Cetuximab | Number of Patients With Dose Limiting Toxicities by NCI-CTCAE | Renal Failure Acute : Grade 4 | 0 Participants |
| NKTR-102 125 mg/m2 + Cetuximab | Number of Patients With Dose Limiting Toxicities by NCI-CTCAE | Renal Failure Acute : Grade 4 | 1 Participants |
| NKTR-102 125 mg/m2 + Cetuximab | Number of Patients With Dose Limiting Toxicities by NCI-CTCAE | Dehydration : Any grade | 1 Participants |
| NKTR-102 125 mg/m2 + Cetuximab | Number of Patients With Dose Limiting Toxicities by NCI-CTCAE | Diarrhoea : Grade 3 | 1 Participants |
| NKTR-102 125 mg/m2 + Cetuximab | Number of Patients With Dose Limiting Toxicities by NCI-CTCAE | Renal Failure Acute : Any grade | 1 Participants |
| NKTR-102 125 mg/m2 + Cetuximab | Number of Patients With Dose Limiting Toxicities by NCI-CTCAE | Dehydration : Grade 3 | 1 Participants |
| NKTR-102 125 mg/m2 + Cetuximab | Number of Patients With Dose Limiting Toxicities by NCI-CTCAE | Diarrhoea : Any grade | 1 Participants |
| Total | Number of Patients With Dose Limiting Toxicities by NCI-CTCAE | Dehydration : Grade 3 | 1 Participants |
| Total | Number of Patients With Dose Limiting Toxicities by NCI-CTCAE | Diarrhoea : Any grade | 2 Participants |
| Total | Number of Patients With Dose Limiting Toxicities by NCI-CTCAE | Renal Failure Acute : Grade 4 | 1 Participants |
| Total | Number of Patients With Dose Limiting Toxicities by NCI-CTCAE | Diarrhoea : Grade 3 | 2 Participants |
| Total | Number of Patients With Dose Limiting Toxicities by NCI-CTCAE | Dehydration : Any grade | 1 Participants |
| Total | Number of Patients With Dose Limiting Toxicities by NCI-CTCAE | Renal Failure Acute : Any grade | 1 Participants |
Secondary
Number of Patients With Overall Response
Complete Response is defined as the disappearance of all target lesions. Partial Response is defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. The best overall response was the best response recorded from the start of the study drug until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
Time frame: 12 months
Population: ITT/Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NKTR-102 100 mg/m2 + Cetuximab | Number of Patients With Overall Response | Progressive Disease | 7 Participants |
| NKTR-102 100 mg/m2 + Cetuximab | Number of Patients With Overall Response | Complete Response | 0 Participants |
| NKTR-102 100 mg/m2 + Cetuximab | Number of Patients With Overall Response | Partial Response | 3 Participants |
| NKTR-102 100 mg/m2 + Cetuximab | Number of Patients With Overall Response | Stable Disease | 2 Participants |
| NKTR-102 125 mg/m2 + Cetuximab | Number of Patients With Overall Response | Stable Disease | 3 Participants |
| NKTR-102 125 mg/m2 + Cetuximab | Number of Patients With Overall Response | Progressive Disease | 1 Participants |
| NKTR-102 125 mg/m2 + Cetuximab | Number of Patients With Overall Response | Partial Response | 0 Participants |
| NKTR-102 125 mg/m2 + Cetuximab | Number of Patients With Overall Response | Complete Response | 0 Participants |
| Total | Number of Patients With Overall Response | Stable Disease | 5 Participants |
| Total | Number of Patients With Overall Response | Complete Response | 0 Participants |
| Total | Number of Patients With Overall Response | Partial Response | 3 Participants |
| Total | Number of Patients With Overall Response | Progressive Disease | 8 Participants |