PRIMARY OVARIAN CANCER TRIALS Flashcards
Study #:GOG 3035/FLORA 5
Phase 3, Double-Blind, Placebo-Controlled Study Comparing Chemo-Immunotherapy (Paclitaxel-Carboplatin- Oregovomab) vs Chemotherapy (Paclitaxel-Carboplatin- Placebo) in Patients With Advanced Epithelial Ovarian, Fallopian Tube or Peritoneal Carcinoma
Schema:
Carbo/Taxol
Cohort 1: Adjuvent Carbo/Taxol+/- oregovomab
Cohort 2 NACT: NACT + Interval Surgery three (3) cycles of chemo +/- oregovoramab
Prior Therapies:
None
HIPEC patients excluded
Measurable Disease:
Debulking surgery must be optimal, R1 or R0
Inclusions:
• Newly diagnosed epithelial adenocarcinoma of ovarian, fallopian tube or peritoneal origin FIGO Stage III or IV disease.
• Eligible histologic epithelial cell types: high grade serous adenocarcinoma, high grade endometrioid adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, or adenocarcinoma not otherwise specified (N.O.S.).
• Cohort 1 – Primary Surgery: Preoperative serum CA-125 levels ≥ 50 U/mL, or in Cohort 2
• Cohort 2 - NACT + Interval Surgery: serum CA-125 levels ≥ 50 U/mL prior to first pre-operative chemotherapy.A3:H6
Exclusions:
•HIPEC excluded
•BRCA1 or BRCA2 germline gene mutation test result with positive, ambiguous or inconclusive result, known BRCA1 and BRCA2 somatic mutations, and known positive germline, or Somatic Homologous Recombination Deficiency (HRD) who will receive PARP inhibitor front-line maintenance therapy
• Subjects with mucinous adenocarcinoma, carcinosarcoma, neuroendocrine, and low-grade adenocarcinoma.
• Active autoimmune disease
• Chronic therapeutic corticosteroid use
• Hx malignancy within 5 years before the first dose
• History or evidence upon physical examination of CNS disease, seizures not controlled with standard medical therapy, or any brain metastases.
•Hx myocardial infarction 6 months
Study #:CASE 3821 HIPEC
*Must have surgery at Main campus
Hyperthermic Intraperitoneal Chemotherapy Mechanisms in Epithelial Ovarian Cancer
Schema:
Primary Objective: Changes in cell populations within the tumor microenvironment in tumors obtained from patients undergoing HIPEC at the time of IDS.
Secondary Objective: To associate HIPEC-induced intratumoral changes with response (PFS, OS)
Schema:
Prior Therapies:
•Received 3 cycles of neoadjuvant chemotherapy using a platinum/taxane based regimen and planning to undergo interval debulking surgery (IDS)
with HIPEC
•Post IDS subjects will receive an additional 3 cycles of adjuvant chemotherapy with a platinum/taxane based regimen at the direction of the treating clinician.
Measurable Disease:
No
Inclusion:
•Advanced epithelial ovarian, fallopian tube, or primary peritoneal (EOC) (≥ FIGO Stage IIB)
•Subjects must have a clinical and/or radiographic response to neoadjuvant chemotherapy to meet HIPEC criteria
• (ECOG) performance status 0-<2 [24]
Exclusion:
•Absence of baseline imaging studies (CT abdomen/pelvis and Chest x-ray minimum) prior to beginning chemotherapy
•No response (clinical or radiographic) to neoadjuvant chemotherapy.
•ECOG >/= 3
Study # LANCE
Laparoscopic cytoreduction After Neoadjuvant ChEmotherapy
(LANCE)
Schema:
Randomized 1:1
• Arm A (experimental arm): patients will have MIS or
• Arm B (reference arm): patients will have a laparotomy
Stratified by:
• Stage of the disease (IIIC vs IV),
• BRCA status (positive vs negative vs unknown,
• Receipt of hyperthermic intraperitoneal chemotherapy (HIPEC) (yes vs no).
Prior Therapies
• Complete or PR to 3 or 4 cycles of NACT, with complete radiologic resolution of
any disease outside the abdominal cavity
• Patients that received only 3 cycles of NACT, must have completed their regimen within 9 weeks. Patients that received 4 cycles of NACT, must have completed their regimen within 12 weeks.
Measurable Disease
NO
Inclusion:
• Stage IIIC or IV, high-grade (serous, endometrioid, clear-cell, transitional carcinomas), invasive epithelial ovarian carcinoma, primary peritoneal carcinoma, or fallopian-tube carcinoma or pathology consistent with high-grade mullerian carcinoma.
• Normalization of CA-125
• < 6 weeks from the last cycle of NACT to interval debulking surgery
• ECOG 0-2
• Disease free of other active malignancies in the previous five years, except basal cell carcinoma of the skin
Exclusion:
• Evidence of tumor not amenable to minimally invasive resection on pre-operative imaging (CT, PET-CT, or MRI) including but not limited to the following findings.
• Failure of improvement of ascites during NACT (trace ascites is allowed)
• Small bowel or gastric tumor involvement
• Colon or rectal tumor involvement
• Diaphragmatic tumor involvement
• Splenic or hepatic surface or parenchymal tumor involvement
• Mesenteric tumor involvement
• Tumor infiltration of the lesser peritoneal sac
• History of psychological, familial, sociological or geographical condition potentially preventing compliance with the study protocol and follow-up schedule
• Inability to tolerate prolonged Trendelenburg position or pneumoperitoneum as deemed by participating institution’s clinicians
•Any other contraindication to MIS as assessed by the clinician
Study #: Trillium/ TTI-622-02
A Phase I/II Study of TTI-622 in Combination with Pegylated Liposomal
Doxorubicin in Patients with Platinum-Resistant Ovarian Cancer
Schema:
Experimental: Dose Escalation
TTI-622 will be administered with initial dose of 12 mg/kg by intravenous infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and 15 in subsequent cycles.
Pegylated Liposomal Doxorubicin (PLD) 40 mg/m^2 by intravenous infusion on Day 1 of each 28-day cycle.
Prior Therapies
Up to 4 prior lines (in the recurrent setting, so the frontline treatment/maintenance therapy does not count towards the 4-line maximum)
-No prior Doxil allowed
Measurable Disease
Yes RECIST 1.1
Inclusion:
•ECOG 0 or 1
•Epithelial ovarian cancer (EOC), fallopian tube carcinoma (FTC) or primary peritoneal carcinomas (PPC).
• Platinum-resistant disease
•Progression with standard of care therapies, including platinum-based therapies, PARPs or bevacizumab in the platinum-sensitive setting or intolerability
•All adverse events from prior treatment must be Grade ≤ 1, except alopecia and stable neuropathy, which must have resolved to Grade ≤ 2 or baseline.
Exclusion:
• Platinum-refractory disease (defined as progression on or within 3 months of completing primary first-line platinum-based treatment)
• Prior treatment with PLD
• Non-epithelial histology, including malignant mixed Mullerian tumors Ovarian tumors with low malignant potential (i.e., borderline tumors), low grade serous ovarian cancer or carcinosarcoma
•Hx acute coronary syndromes.
•Hx of or current Class II, III, or IV heart failure.
•Hx or evidence of known central nervous system (CNS) metastases or carcinomatous meningitis.
•Significant bleeding disorders
•Hx of severe hypersensitivity reactions to antibodies.
Systemic steroid therapy.
•Hx or autoimmune disease that has required systemic treatment
Study #: GOG 3052/VERASTEM
A Phase 2 Study of VS-6766 (Dual RAF/MEK Inhibitor) Alone and In
Combination with Defactinib (FAK Inhibitor) in Recurrent Low-Grade
Serous Ovarian Cancer (LGSOC)
Schema:
• Arm 1: VS-6766 4 mg BIW
• Arm 2: VS-6766 3.2 mg BIW +Defactinib 200 mg BID
Prior Therapy:
•Systemic therapy for Stage 1 disease will not count as prior regimen unless recurrence </= 3 mon.
•At least 1 prior line of PLATINUM systemic therapy for metastatic disease:
•single agent or platinum doublet chemotherapy w/ or w/o bevacizumab, maintenance therapy or radiation therapy; hormonal therapy
•MEK/RAF inhibitor therapy (only one prior line is allowed)
Excluded:
Prior MMAE-derived drugs
Radiotherapy within 21 days
Small molecules, chemotherapy, immunotherapy, or monoclonal antibodies within 28 days
Measurable Disease:
Yes per RECIST 1.1
Inclusion:
•Histologically proven LGSOC (ovarian, peritoneal)
Part A: must have a tumor with known KRAS mutation using a validated testing method prior to enrollment
Part B: all LGSOC subjects irrespective of KRAS mutation status are eligible, but KRAS mutational status must be known by validated method prior to treatment assignment.
Parts A and B: adequate material (as defined in the lab manual) must be available for central confirmation prior to treatment assignment.
•Progression (radiographic or clinical) or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease.
Exclusion:
Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy.
•History of prior malignancy with recurrence <3 years from the time of enrollment.
•Subjects who are appropriate candidates for debulking surgery
•Major surgery within 4 weeks (excluding placement of vascular access), minor surgery within 2 weeks, or palliative radiotherapy within 1 week (7 days) of the first dose of study therapy.
•Warfarin treatment
•SARS-Cov2 infection ≤28 days prior to first dose of study therapy
•Ocular disorders, CHF, class III/ IV cardiac disease
•Inability to swallow oral medications
•Impaired GI absorption, gastrectomy or active IBS
