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FOCUS: PCC + Bevacizumab + CA4P Versus PCC + Bevacizumab + Placebo for Subjects With Platinum Resistant Ovarian Cancer

FOCUS: A Multicenter, Multinational, Double-Blind, 2-Arm, Randomized, Phase 2/3, Study of Physician's Choice Chemotherapy ([PCC] Weekly Paclitaxel or Pegylated Liposomal Doxorubicin [PLD]) Plus Bevacizumab and CA4P Versus PCC Plus Bevacizumab and Placebo for Subjects With Platinum-Resistant, Recurrent Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancer

Status
Terminated
Phases
Phase 2Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02641639
Enrollment
70
Registered
2015-12-29
Start date
2016-06-30
Completion date
2017-10-31
Last updated
2025-03-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Platinum Resistant Ovarian Cancer

Brief summary

This is a multicenter, multinational, randomized, double-blind, 2-arm, parallel-group, Phase 2/3 study to evaluate the efficacy and safety of PCC plus bevacizumab and CA4P versus PCC plus bevacizumab and placebo in subjects with platinum-resistant ovarian cancers (prOC). Subjects with platinum-resistant, recurrent, epithelial ovarian, primary peritoneal or fallopian tube cancer will be randomized 1:1 to receive PCC plus bevacizumab and CA4P or PCC plus bevacizumab and placebo. Subjects will be stratified by selected chemotherapy (PLD vs. paclitaxel), platinum free interval (\< 3 vs. 3 to 6 months from last platinum therapy to subsequent progression), and line of therapy (2nd vs. 3rd). This is a 2-part study, consisting of a Phase 2, exploratory study (Part 1) followed by a Phase 3, pivotal study (Part 2). Both parts of the study will have similar overall design. Approximately 80 subjects will be randomized into Part 1 and approximately 356 subjects will be randomized into Part 2.

Detailed description

This is a multicenter, multinational, randomized, double-blind, 2-arm, parallel-group, Phase 2/3 study to evaluate the efficacy and safety of PCC plus bevacizumab and CA4P versus PCC plus bevacizumab and placebo in subjects with platinum-resistant ovarian cancers (prOC). Subjects with platinum-resistant, recurrent, epithelial ovarian, primary peritoneal or fallopian tube cancer will be randomized 1:1 to receive PCC plus bevacizumab and CA4P or PCC plus bevacizumab and placebo. Subjects will be stratified by selected chemotherapy (PLD vs. paclitaxel), platinum free interval (\< 3 vs. 3 to 6 months from last platinum therapy to subsequent progression), and line of therapy (2nd vs. 3rd). This is a 2-part study, consisting of a Phase 2, exploratory study (Part 1) followed by a Phase 3, pivotal study (Part 2). Both parts of the study will have similar overall design. Approximately 80 subjects will be randomized into Part 1 and approximately 356 subjects will be randomized into Part 2. All subjects randomized will receive bevacizumab 10 mg/kg intravenously (IV) on Days 1 and 15, repeated every 4 weeks (q4wk) and PCC with paclitaxel 80 mg/m2 IV on Days 1, 8, 15 and 22, repeated q4wk, or paclitaxel 80 mg/m2 IV on Days 1, 8, 15, repeated q4wk or PLD 40 mg/m2 IV on Day 1, repeated q4wk. Subjects in the Treatment Arm will also receive CA4P 60 mg/m2 on the same day as bevacizumab (Days 1 and 15, repeated q4wk), while subjects in the Control Arm will receive placebo on those days. Order of dosing will follow the guidance listed below during this study when bevacizumab and CA4P / Placebo are dosed the same day as PCC, * Bevacizumab followed by CA4P / Placebo followed after 1-3 hours by paclitaxel, * PLD followed by bevacizumab followed by CA4P / Placebo Subjects will continue randomized treatment until disease progression, unacceptable toxicity, investigator decision, withdrawal of consent, or sponsor discontinues study for any reason. Subjects will undergo tumor assessments (RECIST) at baseline and every 8 weeks and CA-125 levels at baseline and every 4 weeks. The primary endpoint is PFS. Secondary endpoints include ORR, OS, proportion of subjects who remain progression free at 6, 9, and 12 months, and safety. Endpoints will be compared between the Treatment Arm and the Control arm. The study duration is estimated to last approximately 3 years. This study will have 2 parts with the same overall design. Part 1 will enroll up to approximately 80 subjects and will include multiple interim analyses to test the safety and efficacy assumptions in this specific subject population. Upon meeting certain efficacy criteria in Part 1, the protocol will be amended and additional sites added in order to enroll an additional 356 subjects into Part 2 of the study. Subjects enrolled in Part 2 will be analyzed separately and used as a stand-alone confirmatory efficacy study.

Interventions

CA4P is a synthetic phosphorylated prodrug of CA4, a naturally occurring derivative of the South African willow tree, combretum caffrum. CA4P targets pre-existing tumor vasculature, resulting in an acute, reversible reduction in TBF that leads to central necrosis within tumors.

DRUGPlacebo

Saline for infusion

Sponsors

Mateon Therapeutics
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

Inclusion: 1. Signed informed consent form (ICF) 2. Age ≥ 18 years (Age ≥ 19 years if required by local regulatory authorities) 3. ECOG PS of 0-1 4. Histologically or cytologically-confirmed epithelial ovarian, fallopian tube or primary peritoneal cancer in recurrent stage 5. prOC (platinum-resistant ovarian cancers) defined as progression within \> 1 to \< 6 months (+ 2 weeks) of completing previous cycle of primary platinum-based therapy, or during or within \< 6 months (+ 2 weeks) of starting additional platinum based therapies 6. Received ≥ 1 but ≤ 3 prior platinum-based regimens 7. Measurable disease according to RECIST 1.1 8. Left ventricular ejection fraction (LVEF) greater than or equal to at least 45% at baseline assessment if subject is receiving PLD, and/or anthracycline is a concomitant medication 9. No evidence of active (progressing) brain metastasis. (Treated brain metastasis allowed with a posttreatment magnetic resonance imaging (MRI) or Computed Tomography (CT) of brain showing no active (progressing) brain metastasis). Treatment of brain metastasis may include surgery, radiosurgery (linear accelerator (LINAC), gamma knife), or whole brain irradiation. Surgery for brain metastasis must be \> 8 weeks from study entry 10. Hemoglobin \> 9 g/dl. Erythroid growth factors should not have been used in the 2 weeks prior to study entry. Red blood cell transfusions are permitted to maintain the hemoglobin level \> 9 g/dl 11. Adequate bone marrow function in the investigator's opinion 12. Adequate hepatic function defined by the following: * Total bilirubin \< 2 x Upper Limit of Normal (ULN) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 X ULN for the referenced lab (\< 5 X ULN for subjects with liver metastases) 13. Adequate renal function defined by the following: \- Serum creatinine \< 2 X ULN for the referenced lab 14. Subjects of childbearing potential must have a negative serum pregnancy test prior to study entry and must be practicing a highly effective form of contraception 15. At least 2 weeks since prior radiotherapy and has recovered from any Grade 3 toxicities 16. Life expectancy ≥ 12 weeks Exclusion: 1. Subjects who have received prior CA4P therapy 2. Previously having failed treatment with bevacizumab combined with the intended PCC. \- For clarity: Investigators should not select a bevacizumab + PCC combination for the FOCUS trial if the patient has previously failed that same regimen, however they may select a new PCC regimen to combine with bevacizumab. For example, a patient who failed bevacizumab + weekly paclitaxel would be allowed to enroll in FOCUS only if they are assigned to bevacizumab + PLD for the study. 3. Previous treatment with greater than three traditional chemotherapy treatment regimens 4. Untreated brain metastasis or leptomeningeal brain metastasis 5. Solid organ or bone marrow transplant 6. Primary platinum-refractory disease (defined as progression during dosing or within one (1) month of completing the last cycle of patients first platinum-containing regimen) 7. \> Grade 2 peripheral neuropathy 8. Current thrombotic or hemorrhagic disorder/event or history of prior event within 6 months of start of Screening 9. History of prior cerebrovascular event, (including transient ischemic attack) within 6 months of start of Screening 10. Recent history (within 6 months of start of Screening) of angina pectoris, myocardial infarction (including non-Q wave MI), or NYHA Class III and IV congestive heart failure 11. History of torsade de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (\<60 bpm), heart block (excluding 1st degree block, benign PR interval prolongation only), congenital long QT syndrome or new ST segment elevation or depression or new Q wave on ECG 12. Known uncontrolled HIV infection 13. Uncontrolled, clinically significant active infection 14. Serious non-healing wound, ulcer or bone fracture 15. Subjects with known hypersensitivity to any of the components of CA4P, paclitaxel, PLD, or bevacizumab (paclitaxel and PLD dependent on whether PI plans they will be dosed with that PCC) 16. Subjects who are currently or planning on receiving concurrent investigational therapy or who have received investigational therapy for any indication within 30 days of the first scheduled day of dosing 17. Subjects with any other intercurrent medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a subject's ability to provide informed consent, cooperate and participate in the study, or to interfere with the interpretation of the study results 18. Subjects with other invasive malignancies, with the exception of non-melanoma skin cancer, or with previous cancer treatment that contraindicates this protocol therapy within last 3 years 19. Prior radiation therapy to the pelvis or abdomen within 4 weeks of entry into the study 20. History of fistula, gastrointestinal (GI) perforation or intra-abdominal abscess, or invasive disease/metastases of the bowel which in the investigators opinion may increase the risk of GI perforation with bevacizumab treatment. 21. Uncontrolled hypertension (HTN) \- Sustained BP greater than 150 mmHG SBP / 100 mmHG DBP 22. Uncontrolled elevated proteinuria levels in the investigator's opinion 23. Corrected QT interval (\[QTc\] Fridericia) \> 480 ms 24. Significant vascular disease or recent peripheral arterial thrombosis 25. Subjects with active bleeding or pathologic conditions that carry high risk of bleeding 26. Subjects who are pregnant or lactating

Design outcomes

Primary

MeasureTime frameDescription
Progression Free Survival12 MonthsThe primary efficacy parameter in this study is statistically meaningful PFS, defined as the time from the date of randomization until patient discontinuation or death from any cause.

Secondary

MeasureTime frameDescription
Improvement in Objective Response Rate12 MonthsImprovement in objective response rate (ORR). The ORR will be defined as the proportion of subjects with a confirmed complete response (CR) or confirmed partial response (PR) per RECIST 1.1 criteria, based upon the best response. The ORR will be determined based on investigator assessment according to RECIST 1.1 criteria and/or GCIG CA-125 criteria.
Overall Survival (OS)12 MonthsEvaluation of overall survival (OS)
Proportion of Subjects Who Remain Progression-free at 12 Months12 MonthsAssessment of the proportion of subjects who remain progression-free at 12 months on the regimen of PCC plus bevacizumab and CA4P compared with PCC plus bevacizumab and placebo
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of PCC Plus Bevacizumab and CA4P Versus PCC Plus Bevacizumab and Placebo12 MonthsTo evaluate the Incidence of Treatment-Emergent Adverse Events of PCC plus bevacizumab and CA4P versus PCC plus bevacizumab and placebo as measured by aggregate reporting of the number of patient with abnormal findings on (physical exams, vital signs, laboratory measures, ECG, Eastern Cooperative Oncology Group (ECOG) performance status (PS)) and/or analysis of the incidence of adverse events (AEs) using the National Cancer Institute (NCI)-Common Terminology Criteria for AEs (CTCAE) version 4.03.

Countries

Belgium, Germany, United States

Participant flow

Participants by arm

ArmCount
Fosbretabulin Tromethamine
Physician's choice chemotherapy (weekly Paclitaxel or Pegylated Liposomal Doxorubicin \[PLD\]) plus bevacizumab and CA4P Fosbretabulin tromethamine: CA4P is a synthetic phosphorylated prodrug of CA4, a naturally occurring derivative of the South African willow tree, combretum caffrum. CA4P targets pre-existing tumor vasculature, resulting in an acute, reversible reduction in TBF that leads to central necrosis within tumors.
34
Placebo
Physician's choice chemotherapy (weekly Paclitaxel or Pegylated Liposomal Doxorubicin \[PLD\]) plus bevacizumab and placebo Placebo: Saline for infusion
36
Total70

Baseline characteristics

CharacteristicFosbretabulin TromethaminePlaceboTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
20 Participants19 Participants39 Participants
Age, Categorical
Between 18 and 65 years
14 Participants17 Participants31 Participants
Age, Continuous66.9 years
STANDARD_DEVIATION 8.02
63.2 years
STANDARD_DEVIATION 8.05
65 years
STANDARD_DEVIATION 8.18
Baseline Tumor Diameter Sum (cm)80.1 cm
STANDARD_DEVIATION 64.17
67.5 cm
STANDARD_DEVIATION 40.9
73.7 cm
STANDARD_DEVIATION 53.44
Ethnicity (NIH/OMB)
Hispanic or Latino
2 Participants5 Participants7 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
32 Participants31 Participants63 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants1 Participants1 Participants
Race (NIH/OMB)
Black or African American
4 Participants3 Participants7 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
30 Participants32 Participants62 Participants
Sex: Female, Male
Female
34 Participants36 Participants70 Participants
Sex: Female, Male
Male
0 Participants0 Participants0 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
6 / 344 / 36
other
Total, other adverse events
28 / 3430 / 36
serious
Total, serious adverse events
10 / 3411 / 36

Outcome results

Primary

Progression Free Survival

The primary efficacy parameter in this study is statistically meaningful PFS, defined as the time from the date of randomization until patient discontinuation or death from any cause.

Time frame: 12 Months

ArmMeasureValue (MEAN)
Fosbretabulin TromethamineProgression Free Survival116.9 days
PlaceboProgression Free Survival120.4 days
Secondary

Improvement in Objective Response Rate

Improvement in objective response rate (ORR). The ORR will be defined as the proportion of subjects with a confirmed complete response (CR) or confirmed partial response (PR) per RECIST 1.1 criteria, based upon the best response. The ORR will be determined based on investigator assessment according to RECIST 1.1 criteria and/or GCIG CA-125 criteria.

Time frame: 12 Months

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Fosbretabulin TromethamineImprovement in Objective Response Rate8 Participants
PlaceboImprovement in Objective Response Rate13 Participants
Secondary

Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of PCC Plus Bevacizumab and CA4P Versus PCC Plus Bevacizumab and Placebo

To evaluate the Incidence of Treatment-Emergent Adverse Events of PCC plus bevacizumab and CA4P versus PCC plus bevacizumab and placebo as measured by aggregate reporting of the number of patient with abnormal findings on (physical exams, vital signs, laboratory measures, ECG, Eastern Cooperative Oncology Group (ECOG) performance status (PS)) and/or analysis of the incidence of adverse events (AEs) using the National Cancer Institute (NCI)-Common Terminology Criteria for AEs (CTCAE) version 4.03.

Time frame: 12 Months

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Fosbretabulin TromethamineIncidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of PCC Plus Bevacizumab and CA4P Versus PCC Plus Bevacizumab and Placebo28 Participants
PlaceboIncidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of PCC Plus Bevacizumab and CA4P Versus PCC Plus Bevacizumab and Placebo30 Participants
Secondary

Overall Survival (OS)

Evaluation of overall survival (OS)

Time frame: 12 Months

ArmMeasureCategoryValue (COUNT_OF_PARTICIPANTS)
Fosbretabulin TromethamineOverall Survival (OS)Dies while on study6 Participants
Fosbretabulin TromethamineOverall Survival (OS)Censored28 Participants
PlaceboOverall Survival (OS)Dies while on study4 Participants
PlaceboOverall Survival (OS)Censored32 Participants
Secondary

Proportion of Subjects Who Remain Progression-free at 12 Months

Assessment of the proportion of subjects who remain progression-free at 12 months on the regimen of PCC plus bevacizumab and CA4P compared with PCC plus bevacizumab and placebo

Time frame: 12 Months

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Fosbretabulin TromethamineProportion of Subjects Who Remain Progression-free at 12 Months22 Participants
PlaceboProportion of Subjects Who Remain Progression-free at 12 Months24 Participants

Source: ClinicalTrials.gov · Data processed: Mar 10, 2026