Ovarian Cancer Clinical Trial

Gemcitabine Hydrochloride Alone or With M6620 in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

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.

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Full Description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

I. 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.

V. 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 intravenously (IV) over 30 minutes on days 1 and 8. Cycles 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 as in Arm I and ATR kinase inhibitor M6620 IV over 60-90 minutes on days 2 and 9. Cycles 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.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

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 a line of therapy unless given in the maintenance setting; PARP-inhibitors given as maintenance after platinum therapy do not count as a 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
Leukocytes >= 3,000/microliter (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 m^2 for patients with creatinine levels above institutional normal (within 2 weeks prior to initiation of study treatment)
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
The effects of M6620 (VX-970) on the developing human fetus are unknown; for this reason and because deoxyribonucleic acid (DNA) damage inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, 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

Exclusion Criteria:

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 because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; 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
M6620 (VX-970) is primarily metabolized by the cytochrome P450 3A4 (CYP3A4) enzyme; therefore concomitant administration with strong inhibitors or inducers of CYP3A4 should be avoided; because the lists of these agents are constantly changing, 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 CYP3A4 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 because M6620 (VX-970) and/or gemcitabine are agents with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M6620 (VX-970) and/or gemcitabine, 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 because of the potential for pharmacokinetic interactions with M6620 (VX-970) and/or gemcitabine; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated

Study is for people with:

Ovarian Cancer

Phase:

Phase 2

Estimated Enrollment:

70

Study ID:

NCT02595892

Recruitment Status:

Active, not recruiting

Sponsor:

National Cancer Institute (NCI)

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There are 16 Locations for this study

See Locations Near You

Mayo Clinic Hospital in Arizona
Phoenix Arizona, 85054, United States
Mayo Clinic in Arizona
Scottsdale Arizona, 85259, United States
UC San Diego Moores Cancer Center
La Jolla California, 92093, United States
UC San Diego Medical Center - Hillcrest
San Diego California, 92103, United States
Mayo Clinic in Florida
Jacksonville Florida, 32224, United States
Massachusetts General Hospital Cancer Center
Boston Massachusetts, 02114, United States
Brigham and Women's Hospital
Boston Massachusetts, 02115, United States
Beth Israel Deaconess Medical Center
Boston Massachusetts, 02215, United States
Dana-Farber Cancer Institute
Boston Massachusetts, 02215, United States
Wayne State University/Karmanos Cancer Institute
Detroit Michigan, 48201, United States
Mayo Clinic in Rochester
Rochester Minnesota, 55905, United States
Thomas Jefferson University Hospital
Philadelphia Pennsylvania, 19107, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh Pennsylvania, 15232, United States
Vanderbilt University/Ingram Cancer Center
Nashville Tennessee, 37232, United States
M D Anderson Cancer Center
Houston Texas, 77030, United States
University of Virginia Cancer Center
Charlottesville Virginia, 22908, United States
University of Wisconsin Hospital and Clinics
Madison Wisconsin, 53792, United States

How clear is this clinincal trial information?

Study is for people with:

Ovarian Cancer

Phase:

Phase 2

Estimated Enrollment:

70

Study ID:

NCT02595892

Recruitment Status:

Active, not recruiting

Sponsor:


National Cancer Institute (NCI)

How clear is this clinincal trial information?

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