Summary

for females ages 18 years and up (full criteria)
at La Jolla, California and other locations
study started
Michael T. McHale

Description

Summary

This randomized phase II trial studies how well ATR kinase inhibitor M6620 (M6620) and gemcitabine hydrochloride work compared to standard treatment with gemcitabine hydrochloride alone in treating patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back after a period of improvement (recurrent). ATR kinase inhibitor M6620 may stop the growth of tumor cells by blocking an enzyme needed for cell growth, and may also help gemcitabine hydrochloride work better. Gemcitabine hydrochloride is a drug used in chemotherapy that works to stop the growth of tumor cells by blocking cells from growing and repairing themselves, causing them to die. It is not yet known whether adding ATR kinase inhibitor M6620 to standard treatment with gemcitabine hydrochloride is more effective than gemcitabine hydrochloride alone in treating patients with ovarian, primary peritoneal, or fallopian tube cancer.

Official Title

Phase 2 Study of M6620 (VX-970) in Combination With Gemcitabine Versus Gemcitabine Alone in Subjects With Platinum-Resistant Recurrent Ovarian or Primary Peritoneal Fallopian Tube Cancer

Details

PRIMARY OBJECTIVES:

  1. Assess and compare progression free survival (PFS) between gemcitabine (gemcitabine hydrochloride)/M6620 (VX-970) and gemcitabine alone arms.

SECONDARY OBJECTIVES:

  1. Determine and compare overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) between gemcitabine/M6620 (VX-970) and gemcitabine alone arms.

II. Determine and compare the safety profile of gemcitabine/M6620 (VX-970) and gemcitabine alone regimens.

III. Assess and compare PFS at 6 months between gemcitabine/M6620 (VX-970) and gemcitabine alone arms.

IV. Determine and compare the clinical benefit rate (CBR) between gemcitabine/M6620 (VX-970) and gemcitabine alone arms.

  1. Determine and compare the duration of response (DOR) between gemcitabine/M6620 (VX-970) and gemcitabine alone arms.

VI. Determine and compare cancer antigen (CA)125 reduction by >= 50% between gemcitabine/M6620 (VX-970) and gemcitabine alone arms.

VII. Determine and compare overall survival (OS) between gemcitabine/M6620 (VX-970) and gemcitabine alone arms.

VIII. Determine the ORR for subjects in the gemcitabine alone arm who cross over to the gemcitabine/M6620 (VX-970) arm.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may crossover to Arm II.

ARM II: Patients receive gemcitabine hydrochloride as in Arm I and ATR kinase inhibitor M6620 IV over 60-90 minutes on days 2 and 9. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, and then every 6 months for 2 years.

Keywords

Ovarian Serous Tumor Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Carcinoma Fallopian Tube Neoplasms Ovarian Neoplasms Gemcitabine ATR Kinase Inhibitor M6620 Gemcitabine Hydrochloride Laboratory Biomarker Analysis

Eligibility

You can join if…

Open to females ages 18 years and up

  • Patients must have histologically confirmed high grade serous ovarian or primary peritoneal or fallopian tube cancer; platinum resistant disease is defined as progression within 6 months after last platinum regimen
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) with conventional techniques or as >= 10 mm (>= 1 cm) with spiral computed tomography (CT)scan, magnetic resonance imaging (MRI), or calipers by clinical exam; measurable disease by RECIST version (v)1.1 with at least one measurable target lesion
  • Prior therapy: No line limit but no more than 1 prior regimens in the platinum resistant setting; no prior treatment targeting the ATR/checkpoint kinase 1 (CHK1)pathway and no prior gemcitabine as single agent; hormonal therapies immunotherapy,and antiangiogenic therapies (as single agents) do not count as lines; poly (adenosine diphosphate [ADP]-ribose) polymerases (PARP)-inhibitors count as line of therapy;prior carboplatin/gemcitabine is allowed provided that there was no disease progression within 12 months after completion of the carboplatin/gemcitabine regimen;subjects may begin protocol treatment at least 4 weeks or 5 half-lives, whichever is shorter, after their last dose of chemotherapy or hormonal therapy, assuming they are otherwise eligible
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky >= 70%)
  • Life expectancy of greater than 6 months
  • Within 2 weeks prior to initiation of study treatment: Leukocytes >= 3,000/mcL
  • Within 2 weeks prior to initiation of study treatment: Absolute neutrophil count >=1,500/mcL
  • Within 2 weeks prior to initiation of study treatment: Platelets >= 100,000/mcL
  • Within 2 weeks prior to initiation of study treatment: Total bilirubin within normal institutional limits
  • Within 2 weeks prior to initiation of study treatment: Aspartate aminotransferase(AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Within 2 weeks prior to initiation of study treatment: Creatinine =< upper limit of institutional normal OR creatinine clearance >= 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal

  • Confirmation of availability of a formalin-fixed, paraffin-embedded (FFPE) tumor specimen with adequate tumor tissue (either one paraffin embedded tissue block OR 10 5-micron unstained slides from the block on regular (non-plus) slides and 1 hematoxylin and eosin [H&E] slide)
  • All acute, clinically significant treatment-related toxicity from prior therapy,except for alopecia, must have resolved to grade =< 1 prior to study entry
  • At least 4 weeks since major surgery or radiation therapy
  • Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 6 months after completion of study; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • No known hypersensitivity or contraindication to the components of study treatment(M6620 [VX-970], gemcitabine)
  • Ability to understand and the willingness to sign a written informed consent document

You CAN'T join if...

  • Patients with primary platinum refractory disease, defined as progression while first line platinum based chemotherapy
  • Patients who have had chemotherapy within 4 weeks or five half-lives, whichever is shorter, (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients who have had radiotherapy within 4 weeks
  • Patients who are receiving any other investigational agents
  • Patients with known brain metastases should be excluded from this clinical trial; a scan to confirm the absence of brain metastasis is not required
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to M6620 (VX-970) or gemcitabine
  • Concomitant administration with strong inhibitors or inducers of cytochrome P450,family 3, subfamily A, polypeptide 4 (CYP3A4) should be avoided; it is important to regularly consult a frequently-updated medical reference for a list of drugs to avoid or minimize use of; patients receiving any medications or substances that are inhibitors or inducers of cytochrome P450 3A (CYP3A4 enzyme) are ineligible; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with M6620 (VX-970) and/or gemcitabine
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated

Locations

  • UC San Diego Moores Cancer Center accepting new patients
    La Jolla California 92093 United States
  • University of California San Diego accepting new patients
    San Diego California 92103 United States

Details

Status
accepting new patients
Start Date
Sponsor
National Cancer Institute (NCI)
ID
NCT02595892
Phase
Phase 2
Lead Scientist
Michael T. McHale
Study Type
Interventional
Last Updated
June 11, 2018