Neoplasms

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Antineoplastic Agents

All Drugs and Chemicals

Veliparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Patients receive veliparib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Robert Coleman

This phase II trial studies how well veliparib works in treating patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer that has come back or does not respond to treatment. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To estimate the proportion of patients who have objective tumor response (complete or partial).

II. To determine the frequency and severity of adverse events associated with treatment with veliparib (ABT-888) as assessed by the Active Version of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

SECONDARY OBJECTIVES:

I. To determine the duration of progression-free survival (PFS) and overall survival (OS).

II. To determine the proportion of patients who survive progression-free for at least 6 months.

TERTIARY OBJECTIVES:

I. To explore the association between single nucleotide polymorphisms (SNPs) in deoxyribonucleic acid (DNA) repair genes (e.g., breast cancer \[BRCA\]1, Fanconi) and clinical characteristics, response, and patient outcome (PFS and OS).

OUTLINE:

Patients receive veliparib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Veliparib in Treating Patients With Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

A Phase II Evaluation of the Poly (ADP-Ribose) Polymerase (PARP)-1 and -2 Inhibitor Veliparib (ABT-888) (NSC#737664) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients Who Carry a Germline BRCA1 or BRCA2 Mutation

If the clinical trial goes to the second stage and there is sufficient variability in the SNPs, then patients can be categorized by the nature of their SNPs and assessed for prognostic value through survival analysis (e.g. log-rank tests and Cox proportional hazards modeling). If the variability in SNPs is relatively low, assessment of prognostic value can be conducted with odds ratios of patients responding or surviving progression-free for at least 6 months. These techniques will use exact methods such as Fisher's exact test.

BRCA mutational status will be tabulated against the germline mutation to see what proportion of patients have a mutation reversal within the tumor and whether such reversals can explain resistance to the regimen under study.

Patients with complete and partial tumor response by RECIST V1.1 (per response evaluation criteria in Solid Tumors Criteria (RECIST V1.1) for target lesions and assessed by MRI (CT scan): Complete Response (CR), disappearance of all target lesions (confirmed at \>= 4 weeks); Partial Response (PR) \>= 30% decrease in the sum of the longest diameter of target lesions (confirmed at \>= 4 weeks); Overall Response = CR + PR.

Patients with grade 3 or greater Adverse Events (AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported.

The time from randomization until disease progression, death, or date of last contact. Endpoints are progression or death. Patients who are not observed with an endpoint are censored. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions (and \>= 5 mm increase of target lesions), or a measurable increase in a non-target lesion, or the appearance of new lesions.

This outcome captures whether or not the patient survived progression-free for at least 6 months, and is displayed as a proportion.

NRG Oncology

National Cancer Institute (NCI)

Patients receive veliparib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Correlative studies

Veliparib: Given PO

Treatment (Veliparib)

20-29 years

30-39 years

40-49 years

50-59 years

60-69 years

70-79 years

>=80 years

Age, Customized

Sex: Female, Male

Race (NIH/OMB)

Cell Type

Christopher Purdy on behalf of Mike Sill

Proportion of Patients With Complete and Partial Tumor Response

Proportion of Patients With Adverse Events as Assessed by CTCAE v4.0

Duration of PFS

Duration of OS

The Proportion of Patients Who Survive Progression-free for at Least 6 Months

SNPs With DNA Repair Genes, Tumor Response, PFS, OS, and Patient Demographics (e.g. Age, Race, Tumor Grade)

BRCA Mutation in Primary Tumor Tissue

Overall Study

Digestive System Diseases

Immune System Diseases

Stomach Neoplasms

Hypersensitivity

Genital Neoplasms, Female

Urogenital Neoplasms

Ovarian Diseases

Endocrine Gland Neoplasms

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Endocrine System Diseases

Gonadal Disorders

Male Urogenital Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

Pembrolizumab

Lenvatinib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Participants will receive pembrolizumab 200 milligram (mg) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle plus lenvatinib 20 mg administered orally (PO) once daily (QD) during each 21-day cycle for up to 35 cycles.

200 mg administered by IV infusion on Day 1 of each 21-day cycle.

20 mg administered orally (PO) QD during each 21-day cycle.

Ronnie Shapira, MD

Ronnie Shappira, MD

This is a study of pembrolizumab (MK-3475, KEYTRUDA®) in combination with lenvatinib (E7080) for the treatment of platinum sensitive recurrent ovarian cancer. Participants will receive pembrolizumab and lenvatinib.

This will be a phase-2, open-label, single-arm, single-center study to assess the effect of pembrolizumab and Lenvatinib combination therapy on platinum-sensitive recurrent ovarian cancer (ROC) patients.

Female patients 18 years of age or older with histologically-confirmed epithelial ovarian cancer (EOC) - excluding low grade tumors and mucinous histology - and documented disease recurrence following primary or interval debulking surgery and 1-2 prior lines of chemotherapy (including a frontline platinum-based regimen) and a platinum-free interval greater than 6 months will be eligible to enroll in the study.

Twenty-four patients will be included in the study. The study diagram is shown in Figure 1 and the schedule of assessments (SoA) is shown in Section 6.0. After signing the informed consent, eligible subjects according to the inclusion and exclusion criteria will receive oral Lenvatinib 20 mg once daily (QD) plus intravenous (IV) pembrolizumab 200 mg every three weeks (Q3W) until evident progressive disease by CT (RECIST), or unacceptable toxicity, or until completion of 35 treatment cycles with pembrolizumab.

Disease status will be evaluated radiologically by computed tomography (CT) every 9 weeks, in comparison to pretreatment CT, until progression. In case of study withdrawal due to other reasons, radiological evaluation will be maintained every 9 weeks until disease progression or patient's withdrawal of consent or a new anticancer regimen is given. Patients with contrast media allergy will undergo chest CT without contrast medium as well as abdominal and pelvic magnetic resonance imaging (MRI).

Toxicity will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events Ver. 5.0 (NCI-CTCAE). Dose reductions and modification of Lenvatinib will be performed according to the indications in Section 5.2.3. Pembrolizumab dose will not be reduced but the dose can be delayed for up to 9 weeks in case of toxicity which requires steroid.

treatment and steroids withdrawal (refer to Section 5.2.2 on pembrolizumab dose interruptions). Refer to section 5.2.4 for dose modifications for overlapping toxicities.

Health-related quality of life will also be evaluated. Collateral research will focus on potential biomarkers of response to treatment and on micro- and macro-environmental changes occurring during the course of treatment. To that end, tumor biopsies, stool and vaginal swabs and blood (plasma, serum and peripheral blood mononuclear cells (PBMC)) samples will be collected at Screening and during the study. Analyses will be performed to determine pre- and post-treatment changes as well as differences between responders to treatment and non-responders.

Participants who stop study treatment after receiving 35 administrations of pembrolizumab for reasons other than disease progression or intolerability, or participants who attain a complete response (CR) and stop study treatment may be eligible for up to 1 year of treatment with pembrolizumab (17 cycles) ± Lenvatinib upon experiencing disease progression (Second Course Phase). Participants who complete treatment with pembrolizumab after 35 cycles (approximately 2 years) or CR will continue to receive Lenvatinib alone until disease progression, development of unacceptable toxicity, or withdrawal of consent.

Pembrolizumab and Lenvatinib for Platinum- Sensitive Recurrent Ovarian Cancer

A Phase II, Open Lable, Single Arm, Trial to Determine Efficacy and Safety of Lenvatinib in Combination With Pembrolizumab for Platinum- Sensitive Recurrent Ovarian Cancer

defined as the time from study treatment initiation to the first documented disease progression according to RECIST 1.1 or death from any cause.

defined as the percentage of evaluable patients with complete response (CR) or partial response (PR). Response will be evaluated by the Investigator according to RECIST 1.1.

defined as the time (in months) from initiation of treatment with pembrolizumab and Lenvatinib to subsequent chemotherapy treatment initiation.

defined as the time from study treatment initiation to death due to any cause.

To evaluate the impact of the treatment protocol on health-related quality of life (HR-QoL) as assessed by using the global score of the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30.

All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

Safety and tolerability assessed by CTCAE v5.0.

To evaluate the impact of the treatment protocol on health-related quality of life (HR-QoL) as assessed by using the ovarian cancer-specific protocol, (EORTC) QLQ-OV28 for participants treated with Lenvatinib in combination with pembrolizumab.

All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Veliparib in Treating Patients With Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer	NCT01540565	BRCA1 Mutation ... BRCA2 Mutation ... Ovarian Epithel... Recurrent Fallo... Recurrent Ovari... Recurrent Prima...	Laboratory Biom... Veliparib	18 Years -	National Cancer Institute (NCI)
Pembrolizumab and Lenvatinib for Platinum- Sensitive Recurrent Ovarian Cancer	NCT04519151	Ovarian Neoplas... Carcinoma, Ovar... Neoplasm of Sto... Ovarian Disease... Genital Neoplas... Ovarian Epithel... Urogenital Neop... Neoplasms, Glan...	Pembrolizumab Lenvatinib	18 Years -	Sheba Medical Center

Spots Global Cancer Trial Database for ovarian epithelial tumor