Trial Outcomes & Findings for VEGF Trap and Docetaxel in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer (NCT NCT00436501)

Last Updated: 2019-02-26

Results Overview

Escalating dose levels of VEGF Trap were administered intravenously over three dose levels (2, 4, or 6 mg/kg; one dose every 21 days) to identify the maximum tolerated dose (MTD). The MTD is defined as the highest dose level below which 2 or more patients encounter a dose limiting toxicity (DLT), graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. MTD established on absence of observed DLT(s) in either cycle 0 (single agent) or cycle 1 (combination therapy) of any given dose level.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

58 participants

Primary outcome timeframe

21 day cycle, up to 3 cycles

Results posted on

2019-02-26

Participant Flow

Recruitment Period: January 18, 2007 to September 27, 2010. All recruitment done in medical clinic settings.

Of 58 total participants enrolled at multiple sites, three in the Phase II portion of the study were excluded from the trial.

Participant milestones

Participant milestones
Measure	Phase I VEGF Trap, Docetaxel Phase I VEGF Trap starting dose 2 mg/kg intravenous (IV) over 1 hour on day 1 of course 1, then VEGF Trap IV and Docetaxel 75 mg/m\^2 IV over 1 hour on day 1 in all subsequent courses. Courses repeat every 21 days. Escalating doses of VEGF Trap (2, 4, or 6 mg/kg) until maximum tolerated dose (MTD) determined.	Phase II: VEGF Trap, Docetaxel Phase II VEGF Trap 6 mg/kg (the MTD determined in Phase I) and Docetaxel 75 mg/m\^2 as in Phase I. Courses repeat every 21 days.
Complete Study Participation STARTED	9	49
Complete Study Participation COMPLETED	9	49
Complete Study Participation NOT COMPLETED	0	0
Phase 1: VEGF Trap Escalating Dose STARTED	9	0
Phase 1: VEGF Trap Escalating Dose COMPLETED	9	0
Phase 1: VEGF Trap Escalating Dose NOT COMPLETED	0	0
Phase 2: MTD VEGF Trap + Docetaxel STARTED	0	49
Phase 2: MTD VEGF Trap + Docetaxel COMPLETED	0	46
Phase 2: MTD VEGF Trap + Docetaxel NOT COMPLETED	0	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I VEGF Trap, Docetaxel Phase I VEGF Trap starting dose 2 mg/kg intravenous (IV) over 1 hour on day 1 of course 1, then VEGF Trap IV and Docetaxel 75 mg/m\^2 IV over 1 hour on day 1 in all subsequent courses. Courses repeat every 21 days. Escalating doses of VEGF Trap (2, 4, or 6 mg/kg) until maximum tolerated dose (MTD) determined.	Phase II: VEGF Trap, Docetaxel Phase II VEGF Trap 6 mg/kg (the MTD determined in Phase I) and Docetaxel 75 mg/m\^2 as in Phase I. Courses repeat every 21 days.
Phase 2: MTD VEGF Trap + Docetaxel Withdrawal by Subject	0	2
Phase 2: MTD VEGF Trap + Docetaxel Incomplete Assessment	0	1

Baseline Characteristics

VEGF Trap and Docetaxel in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I VEGF Trap, Docetaxel n=9 Participants Phase I VEGF Trap starting dose 2 mg/kg intravenous (IV) over 1 hour on day 1 of course 1, then VEGF Trap IV and Docetaxel 75 mg/m\^2 IV over 1 hour on day 1 in all subsequent courses. Courses repeat every 21 days. Escalating doses of VEGF Trap (2, 4, or 6 mg/kg) until maximum tolerated dose (MTD) determined.	Phase II VEGF Trap, Docetaxel n=46 Participants Phase II VEGF Trap 6 mg/kg (the MTD determined in Phase I) and Docetaxel 75 mg/m\^2 as in Phase I. Courses repeat every 21 days.	Total n=55 Participants Total of all reporting groups
Age, Continuous	59 years n=5 Participants	58 years n=7 Participants	58 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	46 Participants n=7 Participants	55 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	44 Participants n=7 Participants	53 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	45 Participants n=7 Participants	52 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	9 participants n=5 Participants	46 participants n=7 Participants	55 participants n=5 Participants
Participant Cancer Histology Adenocarcinoma	0 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants
Participant Cancer Histology Clear cell	1 participants n=5 Participants	4 participants n=7 Participants	5 participants n=5 Participants
Participant Cancer Histology Endometrioid	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Participant Cancer Histology Mixed	0 participants n=5 Participants	5 participants n=7 Participants	5 participants n=5 Participants
Participant Cancer Histology Serous	6 participants n=5 Participants	31 participants n=7 Participants	37 participants n=5 Participants
Participant Cancer Histology Transitional cell	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Participant Cancer Histology Unclassified	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants

PRIMARY outcome

Timeframe: 21 day cycle, up to 3 cycles

Outcome measures

Outcome measures
Measure	Phase I VEGF Trap, Docetaxel n=9 Participants Phase I VEGF Trap starting dose 2 mg/kg intravenous (IV) over 1 hour on day 1 of course 1, then VEGF Trap IV and Docetaxel 75 mg/m\^2 IV over 1 hour on day 1 in all subsequent courses. Courses repeat every 21 days. Escalating doses of VEGF Trap (2, 4, or 6 mg/kg) until maximum tolerated dose (MTD) determined.	Phase II: VEGF Trap, Docetaxel Phase II VEGF Trap 6 mg/kg (the MTD determined in Phase I) and Docetaxel 75 mg/m\^2 as in Phase I. Courses repeat every 21 days.
Maximum Tolerated Dose of VEGF Trap (Phase I)	6 mg/kg	—

PRIMARY outcome

Timeframe: Up to 6 months

Frequency of clinical response (partial response or complete response) according to the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR): Disappearance all target lesions; Partial Response (PR): \>/= 30% decrease in sum of longest diameter (LD) of target lesions, reference baseline sum LD; Progressive Disease (PD): \>/= 20% increase in sum of LD of target lesions, reference smallest sum LD recorded since treatment started or appearance of 1+ new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum LD since treatment started.

Outcome measures

Outcome measures
Measure	Phase I VEGF Trap, Docetaxel n=9 Participants Phase I VEGF Trap starting dose 2 mg/kg intravenous (IV) over 1 hour on day 1 of course 1, then VEGF Trap IV and Docetaxel 75 mg/m\^2 IV over 1 hour on day 1 in all subsequent courses. Courses repeat every 21 days. Escalating doses of VEGF Trap (2, 4, or 6 mg/kg) until maximum tolerated dose (MTD) determined.	Phase II: VEGF Trap, Docetaxel n=46 Participants Phase II VEGF Trap 6 mg/kg (the MTD determined in Phase I) and Docetaxel 75 mg/m\^2 as in Phase I. Courses repeat every 21 days.
Number of Participants With Clinical Response (Partial Response or Complete Response) According to the Response Evaluation Criteria in Solid Tumors (RECIST) Complete Response	0 participants	11 participants
Number of Participants With Clinical Response (Partial Response or Complete Response) According to the Response Evaluation Criteria in Solid Tumors (RECIST) Partial Response	2 participants	14 participants

PRIMARY outcome

Timeframe: Time from start of treatment to time of progression, assessed up to 6 years.

Overall survival was defined from the date of study entry until death or date of last contact. Median survival time points calculated in the method of Kaplan-Meier. Standard RECIST criteria followed to evaluate response and progression, and all documented responses required confirmation by imaging, examination, or both, no sooner than 4 weeks after the initial documentation of response. In the absence of new symptoms, response assessment consistently done after two additional cycles of therapy.

Outcome measures

Outcome measures
Measure	Phase I VEGF Trap, Docetaxel n=46 Participants Phase I VEGF Trap starting dose 2 mg/kg intravenous (IV) over 1 hour on day 1 of course 1, then VEGF Trap IV and Docetaxel 75 mg/m\^2 IV over 1 hour on day 1 in all subsequent courses. Courses repeat every 21 days. Escalating doses of VEGF Trap (2, 4, or 6 mg/kg) until maximum tolerated dose (MTD) determined.	Phase II: VEGF Trap, Docetaxel Phase II VEGF Trap 6 mg/kg (the MTD determined in Phase I) and Docetaxel 75 mg/m\^2 as in Phase I. Courses repeat every 21 days.
Median Overall Survival (OS) (Phase II)	26.6 months Interval 13.1 to 49.5	—

PRIMARY outcome

Timeframe: Up to 6 months

The percentage of participants in the Phase II arm with an objective response defined as a measurable response according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Standard RECIST criteria were followed to evaluate response and progression. All documented responses were required to undergo confirmation by imaging, examination, or both, no sooner than 4 weeks after the initial documentation of response. In the absence of new symptoms, this response assessment was consistently done after two additional cycles of therapy.

Outcome measures

Outcome measures
Measure	Phase I VEGF Trap, Docetaxel n=46 Participants Phase I VEGF Trap starting dose 2 mg/kg intravenous (IV) over 1 hour on day 1 of course 1, then VEGF Trap IV and Docetaxel 75 mg/m\^2 IV over 1 hour on day 1 in all subsequent courses. Courses repeat every 21 days. Escalating doses of VEGF Trap (2, 4, or 6 mg/kg) until maximum tolerated dose (MTD) determined.	Phase II: VEGF Trap, Docetaxel Phase II VEGF Trap 6 mg/kg (the MTD determined in Phase I) and Docetaxel 75 mg/m\^2 as in Phase I. Courses repeat every 21 days.
Overall Objective Response Rate According to RECIST (Phase II)	54 percentage of participants	—

PRIMARY outcome

Timeframe: Time from start of treatment to time of progression, assessed up to 6 years.

Progression-Free Survival was calculated from study entry until documented disease, death or date of last contact.

Outcome measures

Outcome measures
Measure	Phase I VEGF Trap, Docetaxel n=46 Participants Phase I VEGF Trap starting dose 2 mg/kg intravenous (IV) over 1 hour on day 1 of course 1, then VEGF Trap IV and Docetaxel 75 mg/m\^2 IV over 1 hour on day 1 in all subsequent courses. Courses repeat every 21 days. Escalating doses of VEGF Trap (2, 4, or 6 mg/kg) until maximum tolerated dose (MTD) determined.	Phase II: VEGF Trap, Docetaxel Phase II VEGF Trap 6 mg/kg (the MTD determined in Phase I) and Docetaxel 75 mg/m\^2 as in Phase I. Courses repeat every 21 days.
Median Progression-Free Survival (PFS) (Phase II)	6.4 months Interval 5.1 to 10.3	—

SECONDARY outcome

Timeframe: Response assessed following treatment (every 3 weeks), up to 6 years. Study duration January 2007 to May 2013.

Population: Number analyzed represents those Phase II participants with response as documented in Outcome Measure 2.

Duration of the response from time response is achieved until disease progression is detected. Response assessed following treatment (every 3 weeks) for disease progression. Study duration January 2007 to May 2013, approximately six and half years.

Outcome measures

Outcome measures
Measure	Phase I VEGF Trap, Docetaxel n=25 Participants Phase I VEGF Trap starting dose 2 mg/kg intravenous (IV) over 1 hour on day 1 of course 1, then VEGF Trap IV and Docetaxel 75 mg/m\^2 IV over 1 hour on day 1 in all subsequent courses. Courses repeat every 21 days. Escalating doses of VEGF Trap (2, 4, or 6 mg/kg) until maximum tolerated dose (MTD) determined.	Phase II: VEGF Trap, Docetaxel Phase II VEGF Trap 6 mg/kg (the MTD determined in Phase I) and Docetaxel 75 mg/m\^2 as in Phase I. Courses repeat every 21 days.
Overall Median Duration of Response (Phase II)	6.0 months Interval 1.8 to 27.0	—

SECONDARY outcome

Timeframe: Up to 6 years

Number of participants with adverse effects of treatment. Frequency and severity of adverse effects of treatment as assessed by NCI CTCAE v3.0 (Phase II)

Outcome measures

Outcome measures
Measure	Phase I VEGF Trap, Docetaxel n=9 Participants Phase I VEGF Trap starting dose 2 mg/kg intravenous (IV) over 1 hour on day 1 of course 1, then VEGF Trap IV and Docetaxel 75 mg/m\^2 IV over 1 hour on day 1 in all subsequent courses. Courses repeat every 21 days. Escalating doses of VEGF Trap (2, 4, or 6 mg/kg) until maximum tolerated dose (MTD) determined.	Phase II: VEGF Trap, Docetaxel n=49 Participants Phase II VEGF Trap 6 mg/kg (the MTD determined in Phase I) and Docetaxel 75 mg/m\^2 as in Phase I. Courses repeat every 21 days.
Number of Participants With Treatment-related Adverse Effects as Assessed by NCI CTCAE v3.0 (Phase II)	9 Participants	46 Participants

SECONDARY outcome

Timeframe: 6 months

Population: Phase I, 2 participants had partial response and 3 were stable disease for a total of 5 responses but only 2 had a Clinical Response (confirmed). Phase II, 46 participants was evaluable out of 49 enrolled for response/toxicity.

Progression-free survival (PFS) defined as number of participants out of total in arm that had no disease progression as measured at 6 months. Standard RECIST criteria used to evaluate response and progression. All documented responses required confirmation by imaging, examination, or both, no sooner than 4 weeks after initial documentation of response. In the absence of new symptoms, response assessment was consistently done after two additional cycles of therapy.

Outcome measures

Outcome measures
Measure	Phase I VEGF Trap, Docetaxel n=9 Participants Phase I VEGF Trap starting dose 2 mg/kg intravenous (IV) over 1 hour on day 1 of course 1, then VEGF Trap IV and Docetaxel 75 mg/m\^2 IV over 1 hour on day 1 in all subsequent courses. Courses repeat every 21 days. Escalating doses of VEGF Trap (2, 4, or 6 mg/kg) until maximum tolerated dose (MTD) determined.	Phase II: VEGF Trap, Docetaxel n=46 Participants Phase II VEGF Trap 6 mg/kg (the MTD determined in Phase I) and Docetaxel 75 mg/m\^2 as in Phase I. Courses repeat every 21 days.
Number of Participants With PFS (Phase II) Partial Response	2 Participants	11 Participants
Number of Participants With PFS (Phase II) No change/Stable Disease	3 Participants	10 Participants
Number of Participants With PFS (Phase II) Progressive Disease	4 Participants	14 Participants
Number of Participants With PFS (Phase II) Complete Response	0 Participants	11 Participants

Adverse Events

Phase I VEGF Trap, Docetaxel

Serious events: 8 serious events

Other events: 9 other events

Deaths: 0 deaths

Phase II: VEGF Trap, Docetaxel

Serious events: 43 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Phase I VEGF Trap, Docetaxel n=9 participants at risk Phase I VEGF Trap starting dose 2 mg/kg intravenous (IV) over 1 hour on day 1 of course 1, then VEGF Trap IV and Docetaxel 75 mg/m\^2 IV over 1 hour on day 1 in all subsequent courses. Courses repeat every 21 days. Escalating doses of VEGF Trap (2, 4, or 6 mg/kg) until maximum tolerated dose (MTD) determined.	Phase II: VEGF Trap, Docetaxel n=46 participants at risk Phase II VEGF Trap 6 mg/kg (the MTD determined in Phase I) and Docetaxel 75 mg/m\^2 as in Phase I. Courses repeat every 21 days.
Blood and lymphatic system disorders Lowered leucocytes	44.4% 4/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	54.3% 25/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Blood and lymphatic system disorders Neutropenia	88.9% 8/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	80.4% 37/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Blood and lymphatic system disorders Prolonged PTT	11.1% 1/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	0.00% 0/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Metabolism and nutrition disorders Lowered magnesium	0.00% 0/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	2.2% 1/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Metabolism and nutrition disorders Raised creatinine	0.00% 0/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	2.2% 1/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Cardiac disorders Hypertension	22.2% 2/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	0.00% 0/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
General disorders Fatigue	44.4% 4/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	50.0% 23/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Respiratory, thoracic and mediastinal disorders Dyspnoea	33.3% 3/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	21.7% 10/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Skin and subcutaneous tissue disorders Skin Ulceration	11.1% 1/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	0.00% 0/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Gastrointestinal disorders Gastrointestinal fistula	0.00% 0/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	2.2% 1/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Nervous system disorders Neuropathy, sensory	0.00% 0/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	2.2% 1/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Nervous system disorders Transient ischaemic attack	0.00% 0/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	2.2% 1/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Gastrointestinal disorders Stomatitis	0.00% 0/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	6.5% 3/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
General disorders Headache	11.1% 1/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	2.2% 1/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).

Other adverse events

Additional Information

Robert Coleman, MD / Professor

UT MD Anderson Cancer Center, Office of Multicenter Clinical Research

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Phase I VEGF Trap, Docetaxel n=9 participants at risk Phase I VEGF Trap starting dose 2 mg/kg intravenous (IV) over 1 hour on day 1 of course 1, then VEGF Trap IV and Docetaxel 75 mg/m\^2 IV over 1 hour on day 1 in all subsequent courses. Courses repeat every 21 days. Escalating doses of VEGF Trap (2, 4, or 6 mg/kg) until maximum tolerated dose (MTD) determined.	Phase II: VEGF Trap, Docetaxel n=46 participants at risk Phase II VEGF Trap 6 mg/kg (the MTD determined in Phase I) and Docetaxel 75 mg/m\^2 as in Phase I. Courses repeat every 21 days.
Blood and lymphatic system disorders Lowered haemoglobin	44.4% 4/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	41.3% 19/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Blood and lymphatic system disorders Lowered platelets	44.4% 4/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	26.1% 12/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Blood and lymphatic system disorders Lowered leucocytes	55.6% 5/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	28.3% 13/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Blood and lymphatic system disorders Neutropenia	11.1% 1/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	2.2% 1/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Blood and lymphatic system disorders Prolonged PTT	22.2% 2/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	6.5% 3/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Metabolism and nutrition disorders Lowered magnesium	33.3% 3/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	41.3% 19/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Metabolism and nutrition disorders Lowered potassium	22.2% 2/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	8.7% 4/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Metabolism and nutrition disorders Raised Alanine transaminase (ALT)	11.1% 1/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	8.7% 4/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Metabolism and nutrition disorders Raised Aspartate aminotransferase (AST)	44.4% 4/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	15.2% 7/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Metabolism and nutrition disorders Raised alkaline phosphatase	0.00% 0/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	23.9% 11/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Metabolism and nutrition disorders Raised creatinine	0.00% 0/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	10.9% 5/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Cardiac disorders Hypertension	55.6% 5/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	10.9% 5/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
General disorders Fatigue	55.6% 5/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	32.6% 15/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Respiratory, thoracic and mediastinal disorders Dyspnoea	33.3% 3/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	43.5% 20/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Skin and subcutaneous tissue disorders Nail changes	22.2% 2/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	21.7% 10/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Skin and subcutaneous tissue disorders Infection, nail beds	0.00% 0/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	10.9% 5/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Eye disorders Watery eyes	11.1% 1/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	47.8% 22/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Respiratory, thoracic and mediastinal disorders Voice changes	55.6% 5/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	23.9% 11/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Skin and subcutaneous tissue disorders Skin Ulceration	11.1% 1/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	0.00% 0/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Infections and infestations Infection	33.3% 3/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	10.9% 5/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Nervous system disorders Neuropathy, sensory	22.2% 2/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	37.0% 17/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Skin and subcutaneous tissue disorders Hand or foot reaction	22.2% 2/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	13.0% 6/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Respiratory, thoracic and mediastinal disorders Nose bleeds	44.4% 4/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	47.8% 22/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Skin and subcutaneous tissue disorders Alopecia	100.0% 9/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	76.1% 35/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
Gastrointestinal disorders Stomatitis	88.9% 8/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	71.7% 33/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).
General disorders Headache	66.7% 6/9 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).	39.1% 18/46 • Adverse events that occur up to 30 days after the last dose of treatment were collected. Among all Phase 2 participants, 307 treatment cycles of 21 days were administered (median 6, range 1-22).