Trial of Pemetrexed and Carboplatin in Patients With Recurrent Ovarian or Primary Peritoneal Cancer
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT00489359
Collaborator
(none)
86
22
2
55.1
3.9
0.1
Study Details
Study Description
Brief Summary
The purpose of this study is to determine efficacy of the combination therapy of pemetrexed and carboplatin as treatment for patients with platinum-sensitive ovarian cancer. This study also includes patients with primary peritoneal cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
86 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1 and 2 Clinical Trial of ALIMTA® (Pemetrexed) in Combination With Carboplatin in Patients With Recurrent Ovarian or Primary Peritoneal Cancer
Study Start Date
:
Jul 1, 2005
Actual Primary Completion Date
:
Feb 1, 2010
Actual Study Completion Date
:
Feb 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Pemetrexed/Carboplatin Phase 1 Pemetrexed was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. |
Drug: Pemetrexed - Phase 1
500, 600, 700, 800, or 900 milligrams per square meter (mg/m^2), administered intravenously (IV), every 21 days x 6 cycles, dose escalate to Maximum Tolerated Dose (MTD)
Other Names:
Drug: Carboplatin - Phase 1
area under the concentration time curve (AUC) 5 or 6 mg/mL*min, administered intravenously (IV), every 21 days x 6 cycles, dose escalation to Maximum Tolerated Dose (MTD)
|
| Experimental: Pemetrexed/Carboplatin Phase 2 Pemetrexed was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. |
Drug: Pemetrexed - Phase 2
Dose determined from Phase 1: 500 mg/m^2, administered IV, every 21 days x 6 cycles
Other Names:
Drug: Carboplatin - Phase 2
Dose determined from Phase 1: AUC 6 mg/mL*min, administered IV, every 21 days x 6 cycles
|
Outcome Measures
Primary Outcome Measures
- Phase 1 - Maximum Tolerated Dose (MTD) of Pemetrexed in Combination With Carboplatin [First treatment to toxicity (up to 18 months)]
MTD was to be determined by increasing doses of pemetrexed up to 900 mg/m^2 and carboplatin Area Under the Concentration-Time Curve (AUC) up to 6 mg/mL*min based on observed pattern of dose limiting toxicity (DLT). See Outcome #3 for DLT. If none of 3 initial participants at a given level experienced a DLT in Cycle 1, enrollment proceeded to the next dose level. If at least 2 participants experienced a DLT in Cycle 1 at a dose level, that dose level was considered the MTD. However, based on results from a different Phase 2 Study (NCT00109096), further dose escalations were not explored.
- Phase 2 - Percentage of Participants With Overall Tumor Response (Response Rate) [baseline to measured progressive disease (PD) (up to 18 months)]
Response is defined as CR (Complete Response) or PR (Partial Response) per Response Evaluation Criteria in Solid Tumor (RECIST criteria). Possible evaluations include: CR: Disappearance of all target lesions. PR: At least a 30% decrease in the size of target lesions. Response rate (%) = (number of patients with CR+PR/number of patients in Phase 2)*100
Secondary Outcome Measures
- Phase 1 - Number of Dose-Limiting Toxicities (DLTs) [baseline through end of Phase 1 (up to 18 months)]
The following toxicities were considered DLT: CTCAE Grade 4 neutropenia (absolute neutrophil count [ANC] <0.5 × 10^9/L lasting ≥7 days. Febrile neutropenia (ANC <1.0 × 10^9/L, fever 38.5°C, and no documented infection). CTCAE Grade 4 thrombocytopenia (platelets <25.0 × 10^9/L). Any hemorrhage with CTCAE Grade ≥3 thrombocytopenia (50.0 × 10^9/L). CTCAE Grade ≥3 nonhematologic toxicity (excluding nausea, vomiting, or CTCAE Grade 3 alanine transaminase (ALT) or aspartate aminotransferase (AST) that returned to baseline prior to next treatment). Treatment delay more than 1 week due to toxicity.
- Phase 1 - Number of Participants With Adverse Events (Toxicity) [baseline measured to progressive disease (up to 18 months)]
A listing of adverse events is located in the Reported Adverse Event module.
- Phase 1 - Recommended Dose of Pemetrexed for Phase 2 [baseline measured to progressive disease (up to 18 months)]
MTD was to be used as Phase 2 recommended dose. MTD was to be determined by increasing doses of pemetrexed up to 900 mg/m^2 based on observed pattern of dose limiting toxicity (DLT: See Outcome #3). If none of 3 initial participants at a given level had a DLT in Cycle 1, enrollment proceeded to next dose level. If at least 2 participants had a DLT in Cycle 1 at a dose level, that dose level was considered the MTD. However, based on results from another Phase 2 Study (NCT00109096), further dose escalations were not explored and dose was selected based on results of that Phase 2 Study.
- Phase 1 - Recommended Area Under the Curve (AUC) Dose of Carboplatin for Phase 2 [baseline measured to progressive disease (up to 18 months)]
MTD was to be used as Phase 2 recommended dose. MTD determined by increasing doses up to AUC 6 mg/mL*min based on pattern of DLT (Outcome #3). If none of 3 initial participants at given level had DLT in Cycle 1, enrollment proceeded to next dose level. If at least 2 participants had DLT in Cycle 1 at dose level, that dose level was considered MTD. However, based on results from Phase 2 Study (NCT00109096), further dose escalations were not explored: carboplatin dose was selected based on standard dose employed in control arm of first-line therapy for epithelial ovarian cancer (Bookman 2006).
- Phase 1 - Number of Participants With Tumor Response [baseline measured to progressive disease (up to 18 months)]
Patients were analyzed by Cancer Antigen-125 (CA-125) response criteria and RECIST guidelines. Possible evaluations include: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the size of target lesions. Progressive Disease (PD): At least a 20% increase in the size of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
- Phase 2 - Time to Response (TTR) [First treatment to response (up to 31 months)]
Response is defined as CR (Complete Response) or PR (Partial Response) per RECIST criteria. Possible evaluations include: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the size of target lesions. Progressive Disease (PD): At least a 20% increase in the size of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
- Phase 2 - Duration of Response (DOR) [time of response to progressive disease (up to 31 months)]
Duration of response is defined as the time from first observation of Complete Response or Partial Response to the first observation of Progressive Disease or death from any cause. For patients who are still alive at the time of analysis, and who do not have Progressive Disease, duration of response will be censored at the date of the last objective progression-free disease assessment.
- Phase 2 - Time to Disease Progression [baseline to measured progressive disease (up to 31 months)]
Time to objective progressive disease (TTPD) is defined as the time from the date of study enrollment to the date of objectively determined Progressive Disease (PD). For patients who die without objective PD (including death from study disease), TTPD will be censored at the date of the last objective progression-free disease assessment. For patients who are still alive at the time of analysis, and who do not have PD, TTPD will be censored at the date of the last objective progression-free disease assessment.
- Phase 2 - Time to Treatment Failure [First treatment to discontinuation of study drug, progressive disease, or death (up to 31 months)]
Time to treatment failure (TTTF) is defined as the time from the date of study enrollment to the date of the first observation of disease progression, death from any cause, or early discontinuation of treatment (any reason). For patients who are alive, progression-free, and have not discontinued early at the time of analysis, TTTF will be censored at the date of the last objective progression-free disease assessment.
- Phase 2 - Overall Survival [baseline to date of death from any cause (up to 31 months)]
Overall survival is defined as the time from the date of study enrollment to the date of death from any cause. This analysis was not done due to the high number of censored patients.
- Phase 2 - Number of Participants With Adverse Events (Toxicity) [baseline through end of Phase 2 (up to 31 months)]
A listing of adverse events is located in the Reported Adverse Event module.
- Phase 2 - Progression-Free Survival [baseline to measured progressive disease (up to 31 months)]
Progression-free survival (PFS) is defined as the time from the date of study enrollment to the date of objectively determined PD or death from any cause, whichever comes first. For patients who are still alive at the time of analysis, and who do not have PD, PFS will be censored at the date of the last objective progression-free disease assessment.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Diagnosis of ovarian or primary peritoneal cancer confirmed by pathology
-
Patients must have recurrent ovarian cancer which is sensitive to platinum therapy
-
Prior radiation therapy is allowed
Measurable disease as defined by the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines, or non-measurable but cancer antigen 125 (CA-125) greater than or equal to 2X upper limit.
Exclusion Criteria:
-
More than 2 lines of therapy for ovarian or primary peritoneal cancer.
-
Pregnant or breast feeding.
-
Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Bahia Blanca | Argentina | B8000HXM | |
| 2 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Buenos Aires | Argentina | C1199ACK | |
| 3 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Ramos Mejia | Argentina | B1704ESN | |
| 4 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Salta | Argentina | 4400 | |
| 5 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Calgary | Alberta | Canada | T2N 4N2 |
| 6 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Toronto | Ontario | Canada | M5G 2M9 |
| 7 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Berlin | Germany | 13353 | |
| 8 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Bonn | Germany | 53127 | |
| 9 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Chemnitz | Germany | D-09116 | |
| 10 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Duesseldorf | Germany | 40489 | |
| 11 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Erlangen | Germany | D-91054 | |
| 12 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Essen | Germany | DE-45145 | |
| 13 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Hamburg | Germany | 22081 | |
| 14 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Jena | Germany | D-07743 | |
| 15 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Kiel | Germany | D-24105 | |
| 16 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Mainz | Germany | 55131 | |
| 17 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Tübingen | Germany | 72076 | |
| 18 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Gdansk | Poland | 80-402 | |
| 19 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Olsztyn | Poland | 10-228 | |
| 20 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Warsaw | Poland | 00909 | |
| 21 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Göteborg | Sweden | 416 85 | |
| 22 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Lund | Sweden | 22241 |
Sponsors and Collaborators
- Eli Lilly and Company
Investigators
- Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00489359
Other Study ID Numbers:
- 9516
- H3E-MC-JMHH
First Posted:
Jun 21, 2007
Last Update Posted:
Jun 16, 2011
Last Verified:
May 1, 2011
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Phase 1 and Phase 2 were conducted in different participants (i.e., Phase 1 participants did not also participate in Phase 2). |
| Arm/Group Title | Pemetrexed/Carboplatin Phase 1 | Pemetrexed/Carboplatin Phase 2 |
|---|---|---|
| Arm/Group Description | Pemetrexed (500, 600, 700, 800, or 900 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin [area under the concentration-time curve (AUC) 5 or 6 mg/mL*min] was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. Participant accrual and dose escalations were dependent upon the observed pattern of dose limiting toxicity (DLT). If none of the 3 initial participants of a given dose level experienced a DLT in Cycle 1, enrollment proceeded to the next dose level. | Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. |
| Period Title: Overall Study | ||
| STARTED | 20 | 66 |
| COMPLETED | 13 | 37 |
| NOT COMPLETED | 7 | 29 |
Baseline Characteristics
| Arm/Group Title | Pemetrexed/Carboplatin Phase 1 | Pemetrexed/Carboplatin Phase 2 | Total |
|---|---|---|---|
| Arm/Group Description | Pemetrexed (500, 600, 700, 800, or 900 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin [area under the concentration-time curve (AUC) 5 or 6 mg/mL*min] was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. Participant accrual and dose escalations were dependent upon the observed pattern of dose limiting toxicity (DLT). If none of the 3 initial participants of a given dose level experienced a DLT in Cycle 1, enrollment proceeded to the next dose level. | Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. | Total of all reporting groups |
| Overall Participants | 20 | 66 | 86 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
56.99
(11.06)
|
57.71
(10.44)
|
57.54
(10.52)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
20
100%
|
66
100%
|
86
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| Caucasian |
20
100%
|
59
89.4%
|
79
91.9%
|
| Hispanic |
0
0%
|
7
10.6%
|
7
8.1%
|
| Region of Enrollment (participants) [Number] | |||
| Canada |
0
0%
|
7
10.6%
|
7
8.1%
|
| Argentina |
0
0%
|
14
21.2%
|
14
16.3%
|
| Poland |
0
0%
|
5
7.6%
|
5
5.8%
|
| Germany |
20
100%
|
31
47%
|
51
59.3%
|
| Sweden |
0
0%
|
9
13.6%
|
9
10.5%
|
| Performance Status (participants) [Number] | |||
| ECOG Status 0 |
3
15%
|
46
69.7%
|
49
57%
|
| ECOG Status 1 |
17
85%
|
20
30.3%
|
37
43%
|
| Tumor Type (participants) [Number] | |||
| Ovarian Cancer |
15
75%
|
61
92.4%
|
76
88.4%
|
| Peritoneal Cancer |
5
25%
|
5
7.6%
|
10
11.6%
|
| Platinum-free interval (participants) [Number] | |||
| <6 months |
0
0%
|
3
4.5%
|
3
3.5%
|
| 6-12 months |
6
30%
|
23
34.8%
|
29
33.7%
|
| >12 months |
14
70%
|
40
60.6%
|
54
62.8%
|
Outcome Measures
| Title | Phase 1 - Maximum Tolerated Dose (MTD) of Pemetrexed in Combination With Carboplatin |
|---|---|
| Description | MTD was to be determined by increasing doses of pemetrexed up to 900 mg/m^2 and carboplatin Area Under the Concentration-Time Curve (AUC) up to 6 mg/mL*min based on observed pattern of dose limiting toxicity (DLT). See Outcome #3 for DLT. If none of 3 initial participants at a given level experienced a DLT in Cycle 1, enrollment proceeded to the next dose level. If at least 2 participants experienced a DLT in Cycle 1 at a dose level, that dose level was considered the MTD. However, based on results from a different Phase 2 Study (NCT00109096), further dose escalations were not explored. |
| Time Frame | First treatment to toxicity (up to 18 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| MTD was not determined in this study, so zero participants were analyzed. |
| Arm/Group Title | Pemetrexed/Carboplatin Phase 1 |
|---|---|
| Arm/Group Description | Pemetrexed (500, 600, 700, 800, or 900 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 5 or AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. Participant accrual and dose escalations were dependent upon the observed pattern of dose limiting toxicity (DLT). If none of the 3 initial participants of a given dose level experienced a DLT in Cycle 1, enrollment proceeded to the next dose level. |
| Measure Participants | 0 |
| Title | Phase 2 - Percentage of Participants With Overall Tumor Response (Response Rate) |
|---|---|
| Description | Response is defined as CR (Complete Response) or PR (Partial Response) per Response Evaluation Criteria in Solid Tumor (RECIST criteria). Possible evaluations include: CR: Disappearance of all target lesions. PR: At least a 30% decrease in the size of target lesions. Response rate (%) = (number of patients with CR+PR/number of patients in Phase 2)*100 |
| Time Frame | baseline to measured progressive disease (PD) (up to 18 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Protocol Qualified (PQ) population. This population includes all patients in the Phase 2 study who met the following requirements: Histologic diagnosis of ovarian or primary peritoneal cancer, no concurrent chemotherapy, treatment with at least 1 dose of pemetrexed or 1 dose of carboplatin, presence of measurable disease as defined by RECIST. |
| Arm/Group Title | Pemetrexed/Carboplatin Phase 2 |
|---|---|
| Arm/Group Description | Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. |
| Measure Participants | 61 |
| Number (95% Confidence Interval) [percentage of participants] |
32.8
164%
|
| Title | Phase 1 - Number of Dose-Limiting Toxicities (DLTs) |
|---|---|
| Description | The following toxicities were considered DLT: CTCAE Grade 4 neutropenia (absolute neutrophil count [ANC] <0.5 × 10^9/L lasting ≥7 days. Febrile neutropenia (ANC <1.0 × 10^9/L, fever 38.5°C, and no documented infection). CTCAE Grade 4 thrombocytopenia (platelets <25.0 × 10^9/L). Any hemorrhage with CTCAE Grade ≥3 thrombocytopenia (50.0 × 10^9/L). CTCAE Grade ≥3 nonhematologic toxicity (excluding nausea, vomiting, or CTCAE Grade 3 alanine transaminase (ALT) or aspartate aminotransferase (AST) that returned to baseline prior to next treatment). Treatment delay more than 1 week due to toxicity. |
| Time Frame | baseline through end of Phase 1 (up to 18 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat (ITT) population - all patients that consented and were successfully screened (note patient may or may not have received treatment; patients that were screen failures were not included in this population). |
| Arm/Group Title | Pemetrexed/Carboplatin Phase 1 |
|---|---|
| Arm/Group Description | Pemetrexed (500, 600, 700, 800, or 900 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 5 or AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. Participant accrual and dose escalations were dependent upon the observed pattern of dose limiting toxicity (DLT). If none of the 3 initial participants of a given dose level experienced a DLT in Cycle 1, enrollment proceeded to the next dose level. |
| Measure Participants | 20 |
| Number of DLT Events |
1
|
| DLT Event: Grade 4 Neutropenia |
1
|
| Title | Phase 1 - Number of Participants With Adverse Events (Toxicity) |
|---|---|
| Description | A listing of adverse events is located in the Reported Adverse Event module. |
| Time Frame | baseline measured to progressive disease (up to 18 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat (ITT) population - all patients that consented and were successfully screened (note patient may or may not have received treatment; patients that were screen failures were not included in this population). |
| Arm/Group Title | Pemetrexed/Carboplatin Phase 1 |
|---|---|
| Arm/Group Description | Pemetrexed (500, 600, 700, 800, or 900 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 5 or AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. Participant accrual and dose escalations were dependent upon the observed pattern of dose limiting toxicity (DLT). If none of the 3 initial participants of a given dose level experienced a DLT in Cycle 1, enrollment proceeded to the next dose level. |
| Measure Participants | 20 |
| Serious Adverse Events |
2
10%
|
| Other Adverse Events |
19
95%
|
| Title | Phase 1 - Recommended Dose of Pemetrexed for Phase 2 |
|---|---|
| Description | MTD was to be used as Phase 2 recommended dose. MTD was to be determined by increasing doses of pemetrexed up to 900 mg/m^2 based on observed pattern of dose limiting toxicity (DLT: See Outcome #3). If none of 3 initial participants at a given level had a DLT in Cycle 1, enrollment proceeded to next dose level. If at least 2 participants had a DLT in Cycle 1 at a dose level, that dose level was considered the MTD. However, based on results from another Phase 2 Study (NCT00109096), further dose escalations were not explored and dose was selected based on results of that Phase 2 Study. |
| Time Frame | baseline measured to progressive disease (up to 18 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat (ITT) population - all patients that consented and were successfully screened (note patient may or may not have received treatment; patients that were screen failures were not included in this population). |
| Arm/Group Title | Pemetrexed/Carboplatin Phase 1 |
|---|---|
| Arm/Group Description | Pemetrexed (500, 600, 700, 800, or 900 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 5 or AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. Participant accrual and dose escalations were dependent upon the observed pattern of dose limiting toxicity (DLT). If none of the 3 initial participants of a given dose level experienced a DLT in Cycle 1, enrollment proceeded to the next dose level. |
| Measure Participants | 20 |
| Number [mg/m^2 (milligrams per square meter)] |
500
|
| Title | Phase 1 - Recommended Area Under the Curve (AUC) Dose of Carboplatin for Phase 2 |
|---|---|
| Description | MTD was to be used as Phase 2 recommended dose. MTD determined by increasing doses up to AUC 6 mg/mL*min based on pattern of DLT (Outcome #3). If none of 3 initial participants at given level had DLT in Cycle 1, enrollment proceeded to next dose level. If at least 2 participants had DLT in Cycle 1 at dose level, that dose level was considered MTD. However, based on results from Phase 2 Study (NCT00109096), further dose escalations were not explored: carboplatin dose was selected based on standard dose employed in control arm of first-line therapy for epithelial ovarian cancer (Bookman 2006). |
| Time Frame | baseline measured to progressive disease (up to 18 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat (ITT) population - all patients that consented and were successfully screened (note patient may or may not have received treatment; patients that were screen failures were not included in this population). |
| Arm/Group Title | Pemetrexed/Carboplatin Phase 1 |
|---|---|
| Arm/Group Description | Pemetrexed (500, 600, 700, 800, or 900 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 5 or AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. Participant accrual and dose escalations were dependent upon the observed pattern of dose limiting toxicity (DLT). If none of the 3 initial participants of a given dose level experienced a DLT in Cycle 1, enrollment proceeded to the next dose level. |
| Measure Participants | 20 |
| Number [mg/mL*min] |
6
|
| Title | Phase 1 - Number of Participants With Tumor Response |
|---|---|
| Description | Patients were analyzed by Cancer Antigen-125 (CA-125) response criteria and RECIST guidelines. Possible evaluations include: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the size of target lesions. Progressive Disease (PD): At least a 20% increase in the size of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. |
| Time Frame | baseline measured to progressive disease (up to 18 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat (ITT) population - all patients that consented and were successfully screened (note patient may or may not have received treatment; patients that were screen failures were not included in this population). |
| Arm/Group Title | Pemetrexed/Carboplatin Phase 1 |
|---|---|
| Arm/Group Description | Pemetrexed (500, 600, 700, 800, or 900 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 5 or AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. Participant accrual and dose escalations were dependent upon the observed pattern of dose limiting toxicity (DLT). If none of the 3 initial participants of a given dose level experienced a DLT in Cycle 1, enrollment proceeded to the next dose level. |
| Measure Participants | 20 |
| Complete Response (CR) |
12
60%
|
| Partial Response (PR) |
4
20%
|
| Stable Disease (SD) |
1
5%
|
| Progressive Disease (PD) |
2
10%
|
| Title | Phase 2 - Time to Response (TTR) |
|---|---|
| Description | Response is defined as CR (Complete Response) or PR (Partial Response) per RECIST criteria. Possible evaluations include: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the size of target lesions. Progressive Disease (PD): At least a 20% increase in the size of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. |
| Time Frame | First treatment to response (up to 31 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Protocol Qualified (PQ) population. This population includes all patients in the Phase 2 study who met the following requirements: Histologic diagnosis of ovarian or primary peritoneal cancer, no concurrent chemotherapy, treatment with at least 1 dose of pemetrexed or 1 dose of carboplatin, presence of measurable disease as defined by RECIST. |
| Arm/Group Title | Pemetrexed/Carboplatin Phase 2 |
|---|---|
| Arm/Group Description | Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. |
| Measure Participants | 20 |
| Median (95% Confidence Interval) [Months] |
1.8
|
| Title | Phase 2 - Duration of Response (DOR) |
|---|---|
| Description | Duration of response is defined as the time from first observation of Complete Response or Partial Response to the first observation of Progressive Disease or death from any cause. For patients who are still alive at the time of analysis, and who do not have Progressive Disease, duration of response will be censored at the date of the last objective progression-free disease assessment. |
| Time Frame | time of response to progressive disease (up to 31 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Protocol Qualified (PQ) population. This population includes all patients in the Phase 2 study who met the following requirements: Histologic diagnosis of ovarian or primary peritoneal cancer, no concurrent chemotherapy, treatment with at least 1 dose of pemetrexed or 1 dose of carboplatin, presence of measurable disease as defined by RECIST. |
| Arm/Group Title | Pemetrexed/Carboplatin Phase 2 |
|---|---|
| Arm/Group Description | Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. |
| Measure Participants | 20 |
| Median (95% Confidence Interval) [Months] |
9.1
|
| Title | Phase 2 - Time to Disease Progression |
|---|---|
| Description | Time to objective progressive disease (TTPD) is defined as the time from the date of study enrollment to the date of objectively determined Progressive Disease (PD). For patients who die without objective PD (including death from study disease), TTPD will be censored at the date of the last objective progression-free disease assessment. For patients who are still alive at the time of analysis, and who do not have PD, TTPD will be censored at the date of the last objective progression-free disease assessment. |
| Time Frame | baseline to measured progressive disease (up to 31 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Protocol Qualified (PQ) population. This population includes all patients in the Phase 2 study who met the following requirements: Histologic diagnosis of ovarian or primary peritoneal cancer, no concurrent chemotherapy, treatment with at least 1 dose of pemetrexed or 1 dose of carboplatin, presence of measurable disease as defined using RECIST. |
| Arm/Group Title | Pemetrexed/Carboplatin Phase 2 |
|---|---|
| Arm/Group Description | Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. |
| Measure Participants | 61 |
| Median (95% Confidence Interval) [Months] |
9.5
|
| Title | Phase 2 - Time to Treatment Failure |
|---|---|
| Description | Time to treatment failure (TTTF) is defined as the time from the date of study enrollment to the date of the first observation of disease progression, death from any cause, or early discontinuation of treatment (any reason). For patients who are alive, progression-free, and have not discontinued early at the time of analysis, TTTF will be censored at the date of the last objective progression-free disease assessment. |
| Time Frame | First treatment to discontinuation of study drug, progressive disease, or death (up to 31 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Protocol Qualified (PQ) population. This population includes all patients in the Phase 2 study who met the following requirements: Histologic diagnosis of ovarian or primary peritoneal cancer, no concurrent chemotherapy, treatment with at least 1 dose of pemetrexed or 1 dose of carboplatin, presence of measurable disease as defined by RECIST. |
| Arm/Group Title | Pemetrexed/Carboplatin Phase 2 |
|---|---|
| Arm/Group Description | Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. |
| Measure Participants | 61 |
| Median (95% Confidence Interval) [Months] |
7.1
|
| Title | Phase 2 - Overall Survival |
|---|---|
| Description | Overall survival is defined as the time from the date of study enrollment to the date of death from any cause. This analysis was not done due to the high number of censored patients. |
| Time Frame | baseline to date of death from any cause (up to 31 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Protocol Qualified (PQ) population. This analysis was not done due to the high number of censored patients. |
| Arm/Group Title | Pemetrexed/Carboplatin Phase 2 |
|---|---|
| Arm/Group Description | Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. |
| Measure Participants | 0 |
| Title | Phase 2 - Number of Participants With Adverse Events (Toxicity) |
|---|---|
| Description | A listing of adverse events is located in the Reported Adverse Event module. |
| Time Frame | baseline through end of Phase 2 (up to 31 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat (ITT) population - all patients that consented and were successfully screened (note patient may or may not have received treatment; patients that were screen failures were not included in this population). |
| Arm/Group Title | Pemetrexed/Carboplatin Phase 2 |
|---|---|
| Arm/Group Description | Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. |
| Measure Participants | 66 |
| Serious Adverse Events |
15
75%
|
| Other Adverse Events |
63
315%
|
| Title | Phase 2 - Progression-Free Survival |
|---|---|
| Description | Progression-free survival (PFS) is defined as the time from the date of study enrollment to the date of objectively determined PD or death from any cause, whichever comes first. For patients who are still alive at the time of analysis, and who do not have PD, PFS will be censored at the date of the last objective progression-free disease assessment. |
| Time Frame | baseline to measured progressive disease (up to 31 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Protocol Qualified (PQ) population. This population includes all patients in the Phase 2 study who met the following requirements: Histologic diagnosis of ovarian or primary peritoneal cancer, no concurrent chemotherapy, treatment with at least 1 dose of pemetrexed or 1 dose of carboplatin, presence of measurable disease as defined by RECIST. |
| Arm/Group Title | Pemetrexed/Carboplatin Phase 2 |
|---|---|
| Arm/Group Description | Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. |
| Measure Participants | 61 |
| Median (95% Confidence Interval) [Months] |
9.4
|
Adverse Events
| Time Frame | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse events are reported regardless of potential relatedness to study drug or Grade (severity). | |||||||||||||
| Arm/Group Title | Pemetrexed 500 + Carboplatin AUC 5 (Phase 1) | Pemetrexed 600 + Carboplatin AUC 5 (Phase 1) | Pemetrexed 600 + Carboplatin AUC 6 (Phase 1) | Pemetrexed 700 + Carboplatin AUC 6 (Phase 1) | Pemetrexed 800 + Carboplatin AUC 6 (Phase 1) | Pemetrexed 900 + Carboplatin AUC 6 (Phase 1) | Pemetrexed 500 + Carboplatin AUC 6 (Phase 2) | |||||||
| Arm/Group Description | Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 5) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. | Pemetrexed (600 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 5) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. | Pemetrexed (600 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. | Pemetrexed (700 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. | Pemetrexed (800 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. | Pemetrexed (900 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. | Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. | |||||||
All Cause Mortality |
||||||||||||||
| Pemetrexed 500 + Carboplatin AUC 5 (Phase 1) | Pemetrexed 600 + Carboplatin AUC 5 (Phase 1) | Pemetrexed 600 + Carboplatin AUC 6 (Phase 1) | Pemetrexed 700 + Carboplatin AUC 6 (Phase 1) | Pemetrexed 800 + Carboplatin AUC 6 (Phase 1) | Pemetrexed 900 + Carboplatin AUC 6 (Phase 1) | Pemetrexed 500 + Carboplatin AUC 6 (Phase 2) | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||||
Serious Adverse Events |
||||||||||||||
| Pemetrexed 500 + Carboplatin AUC 5 (Phase 1) | Pemetrexed 600 + Carboplatin AUC 5 (Phase 1) | Pemetrexed 600 + Carboplatin AUC 6 (Phase 1) | Pemetrexed 700 + Carboplatin AUC 6 (Phase 1) | Pemetrexed 800 + Carboplatin AUC 6 (Phase 1) | Pemetrexed 900 + Carboplatin AUC 6 (Phase 1) | Pemetrexed 500 + Carboplatin AUC 6 (Phase 2) | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/4 (25%) | 0/3 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 15/66 (22.7%) | |||||||
| Blood and lymphatic system disorders | ||||||||||||||
| Anaemia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 3/66 (4.5%) | 5 |
| Pancytopenia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Thrombocytopenia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Cardiac disorders | ||||||||||||||
| Tachycardia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Gastrointestinal disorders | ||||||||||||||
| Abdominal pain | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Ascites | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Constipation | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/66 (0%) | 0 |
| Gastrointestinal haemorrhage | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/66 (0%) | 0 |
| Ileus | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Nausea | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Subileus | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Umbilical hernia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Vomiting | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/66 (3%) | 2 |
| General disorders | ||||||||||||||
| Multi-organ failure | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Immune system disorders | ||||||||||||||
| Drug hypersensitivity | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/66 (4.5%) | 3 |
| Infections and infestations | ||||||||||||||
| Bronchopulmonary aspergillosis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Herpes zoster | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Sepsis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Urinary tract infection | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Zygomycosis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Renal and urinary disorders | ||||||||||||||
| Renal failure | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Renal failure acute | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| Dyspnoea | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/66 (3%) | 2 |
| Pleural effusion | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Pulmonary oedema | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||||||||
| Pemetrexed 500 + Carboplatin AUC 5 (Phase 1) | Pemetrexed 600 + Carboplatin AUC 5 (Phase 1) | Pemetrexed 600 + Carboplatin AUC 6 (Phase 1) | Pemetrexed 700 + Carboplatin AUC 6 (Phase 1) | Pemetrexed 800 + Carboplatin AUC 6 (Phase 1) | Pemetrexed 900 + Carboplatin AUC 6 (Phase 1) | Pemetrexed 500 + Carboplatin AUC 6 (Phase 2) | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/4 (100%) | 3/3 (100%) | 4/4 (100%) | 3/3 (100%) | 3/3 (100%) | 2/3 (66.7%) | 63/66 (95.5%) | |||||||
| Blood and lymphatic system disorders | ||||||||||||||
| Anaemia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 2/4 (50%) | 2 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 19/66 (28.8%) | 32 |
| Leukopenia | 0/4 (0%) | 0 | 2/3 (66.7%) | 2 | 2/4 (50%) | 2 | 1/3 (33.3%) | 2 | 2/3 (66.7%) | 4 | 0/3 (0%) | 0 | 20/66 (30.3%) | 65 |
| Neutropenia | 0/4 (0%) | 0 | 2/3 (66.7%) | 4 | 3/4 (75%) | 3 | 1/3 (33.3%) | 5 | 2/3 (66.7%) | 3 | 0/3 (0%) | 0 | 32/66 (48.5%) | 109 |
| Thrombocytopenia | 2/4 (50%) | 3 | 1/3 (33.3%) | 1 | 3/4 (75%) | 5 | 3/3 (100%) | 3 | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 14/66 (21.2%) | 41 |
| Ear and labyrinth disorders | ||||||||||||||
| Tinnitus | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/66 (3%) | 2 |
| Vertigo | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Eye disorders | ||||||||||||||
| Conjunctivitis | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Eye pain | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/66 (0%) | 0 |
| Keratoconjunctivitis sicca | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 1/4 (25%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Lacrimation increased | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 1/4 (25%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 10/66 (15.2%) | 19 |
| Visual acuity reduced | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 2 | 0/66 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||
| Abdominal pain | 2/4 (50%) | 2 | 2/3 (66.7%) | 7 | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 3 | 0/3 (0%) | 0 | 9/66 (13.6%) | 11 |
| Abdominal pain upper | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 4/66 (6.1%) | 4 |
| Cheilitis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/66 (0%) | 0 |
| Constipation | 4/4 (100%) | 24 | 2/3 (66.7%) | 12 | 2/4 (50%) | 3 | 3/3 (100%) | 9 | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 4 | 21/66 (31.8%) | 39 |
| Diarrhoea | 0/4 (0%) | 0 | 1/3 (33.3%) | 2 | 1/4 (25%) | 1 | 1/3 (33.3%) | 2 | 2/3 (66.7%) | 5 | 0/3 (0%) | 0 | 10/66 (15.2%) | 16 |
| Dry mouth | 2/4 (50%) | 2 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/66 (3%) | 3 |
| Dyspepsia | 2/4 (50%) | 4 | 0/3 (0%) | 0 | 1/4 (25%) | 3 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 5/66 (7.6%) | 6 |
| Flatulence | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Gingivitis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/66 (0%) | 0 |
| Nausea | 4/4 (100%) | 15 | 2/3 (66.7%) | 10 | 3/4 (75%) | 9 | 3/3 (100%) | 12 | 3/3 (100%) | 12 | 2/3 (66.7%) | 5 | 42/66 (63.6%) | 108 |
| Salivary hypersecretion | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/66 (0%) | 0 |
| Stomatitis | 3/4 (75%) | 3 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 2/3 (66.7%) | 5 | 1/3 (33.3%) | 1 | 10/66 (15.2%) | 13 |
| Tongue discolouration | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/66 (0%) | 0 |
| Vomiting | 2/4 (50%) | 2 | 2/3 (66.7%) | 5 | 4/4 (100%) | 8 | 3/3 (100%) | 13 | 3/3 (100%) | 8 | 1/3 (33.3%) | 1 | 27/66 (40.9%) | 45 |
| General disorders | ||||||||||||||
| Chills | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 2/4 (50%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 2 |
| Face oedema | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Fatigue | 3/4 (75%) | 15 | 2/3 (66.7%) | 2 | 4/4 (100%) | 7 | 2/3 (66.7%) | 3 | 3/3 (100%) | 5 | 1/3 (33.3%) | 2 | 33/66 (50%) | 57 |
| Mucosal inflammation | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 10/66 (15.2%) | 18 |
| Oedema peripheral | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 5/66 (7.6%) | 8 |
| Pain | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/66 (0%) | 0 |
| Pyrexia | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 4/66 (6.1%) | 5 |
| Immune system disorders | ||||||||||||||
| Drug hypersensitivity | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 17/66 (25.8%) | 41 |
| Hypersensitivity | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/66 (1.5%) | 2 |
| Infections and infestations | ||||||||||||||
| Cystitis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 4/66 (6.1%) | 4 |
| Influenza | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/66 (0%) | 0 |
| Nasopharyngitis | 2/4 (50%) | 2 | 2/3 (66.7%) | 2 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 7/66 (10.6%) | 7 |
| Investigations | ||||||||||||||
| Alanine aminotransferase increased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 8/66 (12.1%) | 11 |
| Aspartate aminotransferase increased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 6/66 (9.1%) | 10 |
| Blood glucose increased | 0/4 (0%) | 0 | 1/3 (33.3%) | 3 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/66 (0%) | 0 |
| Haemoglobin | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 3 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/66 (3%) | 2 |
| Haemoglobin decreased | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 18/66 (27.3%) | 27 |
| Neutrophil count decreased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 10/66 (15.2%) | 44 |
| Platelet count decreased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 16/66 (24.2%) | 40 |
| White blood cell count decreased | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 4/66 (6.1%) | 15 |
| Metabolism and nutrition disorders | ||||||||||||||
| Anorexia | 0/4 (0%) | 0 | 1/3 (33.3%) | 2 | 2/4 (50%) | 2 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 5/66 (7.6%) | 8 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||
| Arthralgia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 2/4 (50%) | 4 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Back pain | 3/4 (75%) | 3 | 0/3 (0%) | 0 | 2/4 (50%) | 3 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 2/66 (3%) | 2 |
| Bone pain | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Joint swelling | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/66 (0%) | 0 |
| Musculoskeletal pain | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Myalgia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/66 (3%) | 2 |
| Pain in extremity | 0/4 (0%) | 0 | 2/3 (66.7%) | 3 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/66 (3%) | 2 |
| Nervous system disorders | ||||||||||||||
| Ageusia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/66 (0%) | 0 |
| Dizziness | 0/4 (0%) | 0 | 2/3 (66.7%) | 2 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 6/66 (9.1%) | 6 |
| Headache | 2/4 (50%) | 4 | 3/3 (100%) | 6 | 3/4 (75%) | 6 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 2 | 5/66 (7.6%) | 10 |
| Neuropathy peripheral | 1/4 (25%) | 3 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Paraesthesia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 2 | 2/3 (66.7%) | 3 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/66 (0%) | 0 |
| Peripheral sensory neuropathy | 0/4 (0%) | 0 | 2/3 (66.7%) | 2 | 1/4 (25%) | 2 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 6/66 (9.1%) | 7 |
| Polyneuropathy | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Psychiatric disorders | ||||||||||||||
| Insomnia | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 4/66 (6.1%) | 4 |
| Sleep disorder | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 3 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Renal and urinary disorders | ||||||||||||||
| Polyuria | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/66 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| Cough | 1/4 (25%) | 3 | 1/3 (33.3%) | 1 | 1/4 (25%) | 3 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/66 (4.5%) | 3 |
| Dry throat | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/66 (0%) | 0 |
| Dysphonia | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/66 (0%) | 0 |
| Dyspnoea | 1/4 (25%) | 2 | 2/3 (66.7%) | 2 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 4/66 (6.1%) | 6 |
| Epistaxis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/66 (0%) | 0 |
| Nasal mucosal disorder | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/66 (0%) | 0 |
| Oropharyngeal pain | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 2 |
| Rhinitis allergic | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 3 | 0/3 (0%) | 0 | 0/66 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||
| Alopecia | 2/4 (50%) | 2 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 18/66 (27.3%) | 19 |
| Dry skin | 0/4 (0%) | 0 | 2/3 (66.7%) | 2 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 4/66 (6.1%) | 4 |
| Eczema | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/66 (0%) | 0 |
| Erythema | 0/4 (0%) | 0 | 1/3 (33.3%) | 2 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/66 (3%) | 2 |
| Hyperhidrosis | 1/4 (25%) | 3 | 1/3 (33.3%) | 3 | 2/4 (50%) | 6 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/66 (3%) | 2 |
| Leukoplakia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/66 (0%) | 0 |
| Night sweats | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 2/4 (50%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Pruritus | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 6/66 (9.1%) | 10 |
| Rash | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 10/66 (15.2%) | 13 |
| Scar pain | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/66 (0%) | 0 |
| Skin hyperpigmentation | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/66 (1.5%) | 1 |
| Swelling face | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 1/4 (25%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/66 (0%) | 0 |
| Vascular disorders | ||||||||||||||
| Flushing | 1/4 (25%) | 1 | 2/3 (66.7%) | 5 | 3/4 (75%) | 3 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 3 | 6/66 (9.1%) | 12 |
| Hot flush | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/66 (3%) | 2 |
| Lymphoedema | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/66 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 800-545-5979 |
Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00489359
Other Study ID Numbers:
- 9516
- H3E-MC-JMHH
First Posted:
Jun 21, 2007
Last Update Posted:
Jun 16, 2011
Last Verified:
May 1, 2011