A Phase 1/2 Study Evaluating Intermittent and Continuous OSI-906 and Weekly Paclitaxel in Patients With Recurrent Epithelial Ovarian Cancer (and Other Solid Tumors)
Overview
- Phase
- Phase 1
- Intervention
- OSI-906
- Conditions
- Ovarian Cancer
- Sponsor
- Astellas Pharma Inc
- Enrollment
- 152
- Locations
- 46
- Primary Endpoint
- Determine Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a multi-center, randomized, open-label, phase 1/2 study of continuous weekly paclitaxel and escalating doses of intermittent or continuous OSI-906 in patients with recurrent/relapsed ovarian and other solid tumors.
Detailed Description
The phase 1 dose escalation portion will establish the maximum tolerated dose (MTD) in patients with advanced solid tumors. Once the recommended phase 2 dose (RP2D) is established for both schedules, the phase 2 study will begin. Patients with relapsed/recurrent epithelial ovarian cancer will be randomized 1:1:1 to 3 treatment groups.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed epithelial ovarian carcinoma Patients with fallopian or peritoneal cancer will also be eligible
- •Patients with any solid tumor that may be treated with weekly paclitaxel will be eligible for the phase 1 portion
- •For the phase 2 portion, patients must have elevated CA125 levels evaluable/assessable according to Gynecological Cancer Intergroup (GCIG) criteria (ie, \> 70 U/mL) documented by 2 measurements at least 1 week apart
- •Patients must have radiologically confirmed progressive disease by RECIST v1.1 criteria within 6 months prior to randomization. (patients must have measurable disease according to RECIST v1.1)
- •Eastern Cooperative Oncology Group (ECOG) performance status(PS) 0 -1
- •Predicted life expectancy ≥ 12 weeks
- •Patients may have had prior therapy, providing the following conditions are met:
- •Chemotherapy: Prior chemotherapy must have been completed at least 3 weeks prior to study enrollment (6 weeks for mitomycin C, nitrosoureas or high-dose carboplatin \[≥ 600 mg/m²\]and 4 weeks for investigational drugs
- •Patient should have recovered from any drug-related toxicities (with the exception of grade 1 neuropathy and or alopecia)
- •Phase 1: While there is no limit on the number of prior regimens for patients entered into the phase 1 portion, any prior taxane therapy must have been administered on a 3 week schedule
Exclusion Criteria
- •Diabetes mellitus currently requiring medication (eg, insulin or oral hypoglycemics)
- •During the phase 2 portion, patients with histology of abdominal adenocarcinoma of unknown origin or a diagnosis of a borderline ovarian tumor
- •Previous or concurrent malignancies (excluding curatively treated basal or squamous cell carcinoma of the skin or cervical carcinoma in situ) unless the patient has been in remission for at least 3 years
- •History of significant cardiovascular disease unless the disease is well-controlled. Significant cardiac diseases includes second/third degree heart block; significant ischemic heart disease; poorly controlled hypertension; congestive heart failure of New York Heart Association (NYHA) Class II or worse (slight limitation of physical activity; comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea)
- •History of cerebrovascular accident (CVA) within 6 months prior to registration/randomization or that is not stable
- •Prior therapy with an insulin-like growth factor (IGF-1R) inhibitor
- •Use of drugs that have a risk of causing QT interval prolongation within 14 days prior to Day 1 dosing
- •Known or prior hypersensitivity to taxanes in spite of premedication or drugs containing Cremophor
- •Gastro-intestinal abnormalities, including bowel obstruction, inability to take oral medication, requirement for intravenous (IV) alimentation,active peptic ulcer or prior surgical procedures or bowel resection affecting absorption
- •Active infection or serious underlying medical condition (including any type of active seizure disorder within 12 months prior to registration/randomization) that would impair the ability of the patient to receive protocol treatment
Arms & Interventions
Phase 1 Arm A
Intermittent OSI-906 Once Daily (QD) on Days 1 - 3, 8 - 10, and 15 - 17 with paclitaxel on Days 1, 8, and 15 (except Treatment Period 1 (TP 1); in TP 1 OSI-906 on Days 1 - 3, 8 - 10, 15 - 17, and 22 - 24 with paclitaxel on Days 8, 15, and 22)
Intervention: OSI-906
Phase 1 Arm A
Intermittent OSI-906 Once Daily (QD) on Days 1 - 3, 8 - 10, and 15 - 17 with paclitaxel on Days 1, 8, and 15 (except Treatment Period 1 (TP 1); in TP 1 OSI-906 on Days 1 - 3, 8 - 10, 15 - 17, and 22 - 24 with paclitaxel on Days 8, 15, and 22)
Intervention: Paclitaxel
Phase 1 Arm B1
Continuous OSI-906 Twice Daily (BID) (Days 1 - 21) with paclitaxel dosing on Days 1, 8, and 15;(except TP 1; in TP 1 OSI-906 on Days 1 - 3, 8 - 10, 15 - 17, and 22 - 24 with paclitaxel on Days 8, 15 and 22)
Intervention: OSI-906
Phase 1 Arm B1
Continuous OSI-906 Twice Daily (BID) (Days 1 - 21) with paclitaxel dosing on Days 1, 8, and 15;(except TP 1; in TP 1 OSI-906 on Days 1 - 3, 8 - 10, 15 - 17, and 22 - 24 with paclitaxel on Days 8, 15 and 22)
Intervention: Paclitaxel
Phase 1 Arm B2
Continuous OSI-906 BID (Days 1 - 21) with paclitaxel dosing on Days 1, 8, and 15 (except TP 1; in TP 1 OSI-906 on Days 1 - 3, 8 - 10, 5 - 17, and 22 - 24 with paclitaxel on Days 8, 15, and 22); (additional PK sampling on Days 9 or 13 0r 14 for TP 1)
Intervention: OSI-906
Phase 1 Arm B2
Continuous OSI-906 BID (Days 1 - 21) with paclitaxel dosing on Days 1, 8, and 15 (except TP 1; in TP 1 OSI-906 on Days 1 - 3, 8 - 10, 5 - 17, and 22 - 24 with paclitaxel on Days 8, 15, and 22); (additional PK sampling on Days 9 or 13 0r 14 for TP 1)
Intervention: Paclitaxel
Phase 1 Arm B3
Continuous OSI-906 BID (Days 1 - 21) with paclitaxel dosing on Days 1, 8, and 15 with no separation in OSI-906 and paclitaxel dosing (except TP 1; in TP 1 continuous OSI-906 dosing 2 hours prior to the initiation of paclitaxel infusion on Day 8 only, with paclitaxel on Days 8, 15, and 22, and additional PK sampling on Day 9 or 13 or 14)
Intervention: OSI-906
Phase 1 Arm B3
Continuous OSI-906 BID (Days 1 - 21) with paclitaxel dosing on Days 1, 8, and 15 with no separation in OSI-906 and paclitaxel dosing (except TP 1; in TP 1 continuous OSI-906 dosing 2 hours prior to the initiation of paclitaxel infusion on Day 8 only, with paclitaxel on Days 8, 15, and 22, and additional PK sampling on Day 9 or 13 or 14)
Intervention: Paclitaxel
Phase 2 Arm A
Intermittent OSI-906 QD on Days 1 - 3, 8 - 10, and 15 - 17 with paclitaxel on Days 1, 8, and 15
Intervention: OSI-906
Phase 2 Arm A
Intermittent OSI-906 QD on Days 1 - 3, 8 - 10, and 15 - 17 with paclitaxel on Days 1, 8, and 15
Intervention: Paclitaxel
Phase 2 Arm B
Continuous OSI-906 BID from Day 1 onwards with paclitaxel on Days 1, 8, and 15
Intervention: OSI-906
Phase 2 Arm B
Continuous OSI-906 BID from Day 1 onwards with paclitaxel on Days 1, 8, and 15
Intervention: Paclitaxel
Phase 2 Arm C
Paclitaxel on Days 1, 8, and 15
Intervention: Paclitaxel
Phase 2 Arm C Roll-over
Continuous OSI-906 BID from Day 1 onwards
Intervention: OSI-906
Outcomes
Primary Outcomes
Determine Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)
Time Frame: 28 days
Primary outcome measure for Phase 1 portion
Progression Free Survival (PFS)
Time Frame: 36 months
Primary outcome measure for the Phase 2 portion; The time from the date of randomization until date of radiographic disease progression per RECIST v1.1 or until death due to any cause
Secondary Outcomes
- Objective Response Rate (ORR)(36 months)
- Cancer Antigen 125 (CA125) Response Rate(36 months)
- Duration of Response (DOR)(36 months)
- Duration of CA-125 Response (CA-125 DOR)(36 months)
- Overall Survival (OS)(36 months)
- Safety assessed via physician exam, vital signs, clinical laboratory tests, electrocardiograms (ECG), and adverse events(36 months)