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A Phase 2 Study of Avutometinib (VS-6766) Alone and In Combination with Defactinib in Recurrent Low-Grade Serous Ovarian Cancer (LGSOC) (RAMP 201)
EU CTIS ID: 2024-516986-35-00
What this study is testing
Part A: To determine the optimal regimen, either avutometinib monotherapy or avutometinib in combination with defactinib, for subsequent evaluation for efficacy in the expansion phase (Part B) Part B: To determine the efficacy of the optimal regimen identified from Part A Part C: To further evaluate the efficacy of the optimal regimen identified from Part A Part D: To evaluate the efficacy of a lower dose of avutometinib in combination with defactinib
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 1. Female patients ≥ 18 years of age
- 10. Female patients with reproductive potential agree to use highly effective method of contraceptive (per Clinical Trial Facilitation Group [CFTG] recommendations in Section 11.4) during the trial and for 1 month following the last dose of study intervention.
- 2. Histologically proven LGSOC (ovarian, peritoneal) a. The Sponsor's Medical Monitor must review the pathology report prior to the start of treatment b. Adequate pathology material (as defined in the lab manual) must be available prior to enrollment to be used for central confirmation. Central pathological confirmation does not need to be completed prior to enrollment.
- 3. Tumor with known KRAS mutational status using a validated testing method (blood or tissue) prior to treatment assignment. Adequate material (as defined in the lab manual) must be available for central confirmation prior to treatment assignment.
- 4. Progression (radiographic or clinical) or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease. Below are additional prior treatments that are allowed once the requirement of prior platinum therapy is satisfied. a. Prior systemic therapy for metastatic disease (International Federation of Gynecology and Obstetrics [FIGO]stage II-IV) may consist of chemotherapy administered as single-agent or a platinum or another chemotherapy doublet with or without bevacizumab, with or without maintenance therapy or radiation therapy; hormonal therapy; and/or MEK/RAF inhibitor therapy. b. Only one prior line of MEK/RAF inhibitor therapy is allowed.
- 5. Measurable disease according to RECIST 1.1.
You likely can't join if
- 1. Systemic anti-cancer therapy within 4 weeks of the first dose of study intervention.
- 10. For patients with prior MEK exposure, Grade 4 toxicity deemed related to the MEK inhibitor.
- 11. Known hepatitis B, hepatitis C or human immunodeficiency virus infection that is active and/or requires therapy.
- 12. Active skin disorder that has required systemic therapy within the past year.
- 13. History of rhabdomyolysis.
- 2. Co-existing high-grade ovarian cancer or another histology.
See the full eligibility criteria
Who can join
- 1. Female patients ≥ 18 years of age
- 10. Female patients with reproductive potential agree to use highly effective method of contraceptive (per Clinical Trial Facilitation Group [CFTG] recommendations in Section 11.4) during the trial and for 1 month following the last dose of study intervention.
- 2. Histologically proven LGSOC (ovarian, peritoneal) a. The Sponsor's Medical Monitor must review the pathology report prior to the start of treatment b. Adequate pathology material (as defined in the lab manual) must be available prior to enrollment to be used for central confirmation. Central pathological confirmation does not need to be completed prior to enrollment.
- 3. Tumor with known KRAS mutational status using a validated testing method (blood or tissue) prior to treatment assignment. Adequate material (as defined in the lab manual) must be available for central confirmation prior to treatment assignment.
- 4. Progression (radiographic or clinical) or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease. Below are additional prior treatments that are allowed once the requirement of prior platinum therapy is satisfied. a. Prior systemic therapy for metastatic disease (International Federation of Gynecology and Obstetrics [FIGO]stage II-IV) may consist of chemotherapy administered as single-agent or a platinum or another chemotherapy doublet with or without bevacizumab, with or without maintenance therapy or radiation therapy; hormonal therapy; and/or MEK/RAF inhibitor therapy. b. Only one prior line of MEK/RAF inhibitor therapy is allowed.
- 5. Measurable disease according to RECIST 1.1.
- 6. An Eastern Cooperative Group (ECOG) performance status ≤ 1.
- 7.Must have adequate organ function defined by the following laboratory parameters: a. Adequate hematologic function including: hemoglobin [Hb] ≥9.0 g/dL; platelets ≥100,000/mm3; and absolute neutrophil count [ANC] ≥ 1500/mm3. If a red blood cell transfusion has been administered the Hb must remain stable and ≥9 g/dL for at least 1 week prior to first dose of study intervention. b. Adequate hepatic function: (i) total bilirubin ≤1.5 × upper limit of normal [ULN] for the institution; patients with Gilbert syndrome may enroll if total bilirubin is <3.0 mg/dL (51 μmol/L) upon discussion with Medical Monitor: (ii) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN (or < 5 x ULN in patients with liver metastases. c. Adequate renal function with creatinine clearance rate of ≥50 mL/min as calculated by the Cockcroft-Gault formula or serum creatinine of ≤ 1.5 x ULN. d. International normalized ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) ≤ 1.5 x ULN in the absence of anticoagulation or therapeutic levels in the presence of anticoagulation. e. Albumin ≥3.0 g/dL (451 μmol/L). f. Creatine phosphokinase (CPK) ≤2.5 x ULN. g. Adequate cardiac function with left ventricular ejection fraction ≥ 50% by echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan.
- 8. Baseline QTc interval < 460 ms (average of triplicate readings) (Common Terminology Criteria for Adverse Events [CTCAE] Grade 1) using Fredericia's QT correction formula. NOTE: This criterion does not apply to patients with a right or left bundle branch block.
- 9. Adequate recovery from toxicities related to prior treatments to at least Grade 1 by CTCAE v 5.0. Exceptions include alopecia and peripheral neuropathy Grade ≤2. Patients with other toxicities that are stable on supportive therapy may be allowed to participate with prior approval by the Sponsor.
What rules you out
- 1. Systemic anti-cancer therapy within 4 weeks of the first dose of study intervention.
- 10. For patients with prior MEK exposure, Grade 4 toxicity deemed related to the MEK inhibitor.
- 11. Known hepatitis B, hepatitis C or human immunodeficiency virus infection that is active and/or requires therapy.
- 12. Active skin disorder that has required systemic therapy within the past year.
- 13. History of rhabdomyolysis.
- 2. Co-existing high-grade ovarian cancer or another histology.
- 3. History of prior malignancy with recurrence <3 years from the time of enrollment. Patients with basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, and in situ cervical cancer that has undergone potentially curative therapy with no evidence of disease recurrence for >/=1 year since completion of appropriate therapy may be included. Patients with other malignancies associated with very low risk of metastasis or death may be included upon discussion with the Medical Monitor
- 4. Patients who are deemed in the opinion of their treating physician to be appropriate candidates for a debulking surgery. These patients should preferentially receive surgery prior to consideration of trial therapy.
- 5. 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 intervention.
- 6. Treatment with warfarin. Patients on warfarin for deep vein thrombosis/pulmonary embolism can be converted to low-molecular-weight heparin or direct oral anticoagulants (DOACs).
- 7. Exposure to medications (with or without prescriptions), supplements, herbal remedies, or foods with potential for drug-drug interactions with study interventions within 5 half-lives (if known) or 14 days prior to the first dose of study intervention, including: a. Strong CYP3A4 inhibitors or inducers, due to potential drug-drug interactions with bothavutometinib and defactinib. b. Strong CYP2C9 inhibitors or inducers, due to potential drug-drug interactions with defactinib. Not applicable if and when patients randomized to avutometinib monotherapy. c. Strong P-glycoprotein (P-gp) inhibitors or inducers, due to potential drug-drug interactions with both avutometinib and defactinib. d. Strong breast cancer resistance protein (BCRP) inhibitors or inducers, due to potential drug-drug interactions with avutometinib or defactinib.
- 8. Symptomatic brain metastases requiring steroids or other interventions. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 2 weeks prior to first dose of study intervention, and are neurologically stable, with no evidence of interim progression. Patients with new asymptomatic CNS metastases detected during the screening period must receive radiation therapy and/or surgery for CNS metastases. Following treatment, these patients may then be eligible if all other criteria are met.
- 9. Known severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) infection (clinical symptoms) </= 28 days prior to first dose of study intervention.
The study team makes the final eligibility decision.
Where it's taking place
- United States
- Canada
- United Kingdom
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling female, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United States; Canada; United Kingdom. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.