Tshwane, South Africa

Heated Intraperitoneal Chemotherapy Followed by Niraparib for Ovarian, Primary Peritoneal and Fallopian Tube Cancer

S1803, Lenalidomide +/- Daratumumab/rHuPh20 as Post-ASCT Maintenance for MM w/MRD to Direct Therapy Duration

Lung-MAP: A Master Screening Protocol for Previously-Treated Non-Small Cell Lung Cancer

Primary Objective of the Master Protocol (LUNGMAP) The primary objective of this screening study is to test patient specimens to determine eligibility for participation in the biomarker-driven and non-matched sub-studies included within the Lung-MAP umbrella protocol. Secondary Objectives 1. Screening Success Rate Objective To evaluate the screen success rate defined as the percentage of screened patients that register for a therapeutic sub-study. Screen success rates will be evaluated for the total screened population and by the subset of patients screened following progression on previous therapy or pre-screened on current therapy. 2. Translational Medicine Objectives 1. To evaluate circulating tumor DNA (ctDNA) and compare to the FMI Foundation tissue molecular profiling results in patients who submit a new biopsy for screening. 2. To establish a tissue/blood repository. Ancillary Study S1400GEN Objectives The Lung-MAP Screening Study includes an ancillary study evaluating patient and physician attitudes regarding the return of somatic mutation findings suggestive of a germline mutation. Participation in this study is optional. 1. Primary Objective To evaluate patient attitudes and preferences about return of somatic mutation findings suggestive of a germline mutation in the Lung-MAP Screening Study. 2. Secondary Objectives 1. To evaluate Lung-MAP study physician attitudes and preferences about return of somatic mutation findings suggestive of a germline mutation in the Lung-MAP Screening Study. 2. To evaluate Lung-MAP patients' and study physicians' knowledge of cancer genomics. 3. To evaluate Lung-MAP patients' and study physicians' knowledge of the design of the Lung-MAP Screening Study. 4. To explore whether physician and patient knowledge of cancer genomics and attitudes and preferences about return of genomic profiling findings are correlated.

Lenalidomide, and Dexamethasone With or Without Daratumumab in Treating Patients With High-Risk Smoldering Myeloma

PRIMARY OBJECTIVES: I. To compare overall survival in patients with high-risk smoldering multiple myeloma randomized to daratumumab-lenalidomide (revlimid)-dexamethasone or revlimid-dexamethasone. SECONDARY OBJECTIVES: I. To compare progression-free survival and response rates between arms. II. To evaluate safety and compare toxicity rates between arms. III. To monitor incidence of infusion-related reactions over the first cycle of daratumumab. IV. To evaluate stem cell mobilization failure and early stem cell mobilization feasibility. EXPLORATORY OBJECTIVES: I. To measure treatment exposure and adherence. II. To estimate treatment duration and time to progression. PATIENT-REPORTED OUTCOMES OBJECTIVES: I. To compare change in health-related quality of life (Functional Assessment of Cancer Therapy [FACT]- General [G]]) from baseline to end of study therapy between arms. II. To compare change in FACT-G scores from treatment end to 6-months post-treatment end between arms. III. To describe changes in FACT-G scores over study therapy and shortly after treatment discontinuation and evaluate correlation with survival. IV. To evaluate attributes of select patient reported treatment-emergent symptomatic adverse events (Patient Reported Outcomes [PRO]-Common Terminology Criteria for Adverse Events [CTCAE]) longitudinally. V. To derive an overall PRO-CTCAE score at each assessment time point. VI. To measure the likelihood of medication adherence (ASK-12) at 6 month intervals throughout treatment. VII. To assess the association of overall PRO-CTCAE score with FACT-G score. VIII. To compare select PRO-CTCAE items and related provider-reported CTCAEs. IX. To evaluate association between treatment adherence and Adherence Starts with Knowledge 12 (ASK-12) score. X. To assess correlation of treatment adherence and ASK-12 score with FACT-G score. XI. To tabulate PRO compliance and completion rates. LABORATORY OBJECTIVES: I. To compare minimal residual disease negative rate after 12 cycles of study therapy between arms. II. To compare minimal residual disease (MRD) positive to negative conversion rates from 12 cycles to end of treatment between arms. III. To examine patterns of change in minimal residual disease levels during study therapy. IV. To evaluate agreement and discordance between methods determining disease-free status. V. To assess the prognostic value of minimal residual disease status at 12 cycles for overall and progression-free survival. IMAGING OBJECTIVES: I. To evaluate the association of baseline fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging with progression-free survival. II. To assess the ability of baseline FDG-PET/CT to predict minimal residual disease status after 12 cycles of study therapy and at the end of study therapy. III. To describe the results of subsequent FDG-PET/CT imaging studies in the subset of patients with baseline abnormal FDG-PET/CT, and to associate these results with progression-free survival (PFS). OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive daratumumab intravenously (IV) on days 1, 8, 15, and 22 of courses 1-2, days 1 and 15 of courses 3-6, and day 1 of courses 7-24. Patients also receive lenalidomide orally (PO) daily on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22 in courses 1-12. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive lenalidomide PO daily on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22 of courses 1-12. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. After completion of study, patients will be followed up every 3, 6 or 12 months for up to 15 years from study entry.

Melanoma Margins Trial-II: 1cm v 2cm Wide Surgical Excision Margins for AJCC Stage II Primary Cutaneous Melanoma

This study will determine whether there is a difference in disease-free survival rates for patients with primary cutaneous melanoma with Breslow thickness > 2mm or 1-2mm with ulceration (pT2b-pT4b, AJCC 8th edition), treated with either a 1cm excision margin or 2cm margin. The study is designed to be able to prove or disprove that there is no difference in risk of the tumour recurring around the scar or anywhere else in the body between the two groups of patients. If the study shows no risk of tumour recurrence then we will also be able to determine how much of an impact the narrower excision has on patients in terms of improved quality of life and reduced side effects from the surgery and melanoma disease. This trial will also evaluate and determine the economic impact of narrower excision margins on the health services and society in general.

Comparing Proton Therapy to Photon Radiation Therapy for Esophageal Cancer

PRIMARY OBJECTIVES: I. To determine if overall survival (OS) is improved with proton beam radiation therapy (PBT) treatment as compared to intensity modulated photon radiation therapy (IMRT) as part of planned protocol treatment for patients with esophageal cancer. II. To determine if OS with PBT is non-inferior to IMRT as part of planned protocol treatment and that there will be less grade 3+ cardiopulmonary toxicity with PBT than with IMRT. SECONDARY OBJECTIVES: I. To compare the symptom burden and impact on functioning of patients between treatment modalities based on Patient Reported Outcome (PRO) measures of symptoms using MD Anderson Symptom Inventory (MDASI) and Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue. II. To compare the Quality-Adjusted Life Years (QALY) using EuroQol five-dimensional questionnaire (EQ5D) as a health outcome between PBT and IMRT, if the protocol primary endpoint is met. III. To assess the pathologic response rate between PBT and IMRT. IV. To assess the cost-benefit economic analysis of treatment between radiation modalities. V. To compare the length of hospitalization after protocol surgery between PBT and IMRT. VI. To compare the incidence of grade 4 lymphopenia during chemoradiation between PBT and IMRT. VII. To compare lymphocyte nadir at first follow-up visit after completion of chemoradiation between PBT & IMRT. VIII. To estimate the locoregional failure, distant metastatic free survival, and progression-free survival of patients treated with PBT versus IMRT. IX. To compare incidence of both early (< 90 days from treatment start) and late (≥ 90 days from treatment start) cardiovascular and pulmonary events between PBT versus IMRT. X. To compare the Total Toxicity Burden (TTB) of IMRT versus PBT based on a composite index of 9 individual cardiopulmonary toxicities. EXPLORATORY OBJECTIVES: I. To collect biospecimens for future analyses, for example to assess cardiac and inflammatory biomarkers in association with treatment complications. OUTLINE: Patients are randomized to 1 of 2 groups. GROUP I: Patients undergo PBT over 28 fractions 5 days a week for 5.5 weeks. Patients also receive paclitaxel intravenously (IV) and carboplatin IV on days 1, 8, 15, 22, 29, and 36 while undergoing PBT. GROUP II: Patients undergo IMRT over 28 fractions 5 days a week for 5.5 weeks. Patients also receive paclitaxel IV and carboplatin IV on days 1, 8, 15, 22, 29, and 36 while undergoing IMRT. In both groups, within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion. After completion of study treatment, patients are followed up every 3-6 months for 3 years and then annually thereafter.

Genetic Testing in Guiding Treatment for Patients With Brain Metastases

PRIMARY OBJECTIVES: I. To determine the activity of a CDK inhibitor in patients with progressive brain metastases derived from lung cancer, breast cancer, and other cancers harboring actionable genetic alterations associated with sensitivity to CDK inhibitors as measured by response rate (Response Assessment in Neuro-Oncology [RANO] criteria). II. To determine the activity of a PI3K inhibitor in patients with progressive brain metastases derived from lung cancer, breast cancer, and other cancers harboring actionable genetic alterations in the PI3K pathway as measured by response rate (RANO criteria). III: To determine the activity of an NTRK/ROS1 inhibitor in patients with progressive brain metastases derived from lung cancer harboring actionable NTRK/ROS1 gene fusions as measured by response rate (RANO criteria). IV. To determine the activity of an KRAS G12C inhibitor in patients with progressive brain metastases derived from lung cancer, and other cancers harboring a KRAS G12C mutation as measured by response rate (RANO criteria). SECONDARY OBJECTIVES: I. To evaluate the systemic response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria in each of the cohorts determined by treatment and primary cancer type. II. To evaluate the clinical benefit rate (complete response [CR] + partial response [PR] + stable disease [SD]) by Brain Metastases (BM)-RANO for central nervous system (CNS) in each of the cohorts determined by treatment and primary cancer type. III. To evaluate the clinical benefit rate (CR + PR + SD) by RECIST for extracranial disease in each of the cohorts determined by treatment and primary cancer type. IV. To evaluate the duration of response by BM-RANO in each of the cohorts determined by treatment and primary cancer type. V. To evaluate the duration of response by RECIST in each of the cohorts determined by treatment and primary cancer type. VI. To evaluate the progression-free survival for intracranial disease in each of the cohorts determined by treatment and primary cancer type. VII. To evaluate the progression-free survival for extracranial disease in each of the cohorts determined by treatment and primary cancer type. VIII. To evaluate the site of first progression (CNS versus [vs] non-CNS) in each of the cohorts determined by treatment and primary cancer type. IX. To evaluate the overall survival in each of the cohorts determined by treatment and primary cancer type. X. To evaluate the toxicity profile of agents in patients with brain metastases in each of the cohorts determined by treatment and primary cancer type. OUTLINE: Patients are assigned to 1 of 4 arms. ARM I (CDK GENE MUTATION): Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II (PI3K GENE MUTATION): Patients receive PI3K inhibitor paxalisib PO once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM III (NTRK/ROS1 GENE MUTATION): Patients receive entrectinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM IV (KRAS G12C MUTATION): Patients receive adagrasib (MRTX849) PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 8 weeks for 2 years, then every 3 months for years 3-4, and then every 6 months thereafter for up to 5 years after registration.

Regional Radiotherapy in Biomarker Low-Risk Node Positive and T3N0 Breast Cancer

Women with node positive breast cancer normally will receive endocrine therapy and some may receive chemotherapy to help prevent the cancer from coming back. Many women will also receive radiotherapy to the whole breast/chest area and the surrounding lymph glands (called regional radiotherapy). No one really knows whether patients with low risk breast cancer need to receive regional radiotherapy. Some women may be getting regional radiotherapy who do not need it. These women may be exposed to the side effects of their treatment without benefit.

Testing the Use of Combination Therapy in Adult Patients With Newly Diagnosed Multiple Myeloma, the EQUATE Trial

PRIMARY OBJECTIVE: I. To determine if bortezomib, daratumumab and hyaluronidase-fihj (daratumumab), lenalidomide and dexamethasone (Btz-DRd) consolidation followed by daratumumab and lenalidomide (DR) maintenance after standard induction therapy with daratumumab, lenalidomide and dexamethasone (DRd) results in superior overall survival compared to DRd consolidation followed by DR maintenance, in minimal residual disease (MRD) positive patients. SECONDARY OBJECTIVES: I. To determine if Btz-DRd consolidation followed by DR maintenance after standard induction therapy with DRd results in superior overall survival compared to DRd consolidation followed by DR maintenance in MRD negative patients. II. To determine if Btz-DRd consolidation followed by DR maintenance after standard induction therapy with DRd results in superior progression-free survival compared to DRd consolidation followed by DR maintenance in both MRD positive and MRD negative patients. III. To describe and compare the incidence of toxicities during consolidation between Btz-DRd and DRd arms. IV. To assess the improvement in MRD negative rate with consolidation among patients who are MRD positive after induction. V. To assess the sustained MRD negative rate among patients who are MRD negative after induction. PATIENT REPORTED OUTCOMES (PRO) OBJECTIVES: I. To quantify the extent to which the addition of bortezomib to DRd over consolidation treatment contributes to neuropathy and associated physical and functional impairments. (Primary PRO Objective) II. To evaluate the rate of resolution of neurotoxicity and associated physical and functional impairments following completion of consolidation therapy. (Secondary PRO Objective) III. To investigate the relationship between MRD status and patient reported health-related quality of life outcomes. (Exploratory PRO Objective) IV. To evaluate attributes of select patient reported treatment-emergent symptomatic adverse events (PRO- Common Terminology Criteria for Adverse Events [CTCAE]) longitudinally and compare responses with provider-reported adverse events. (Exploratory PRO Objective) V. To tabulate PRO compliance and completion rates. (Exploratory PRO Objective) IMAGING OBJECTIVES: I. To evaluate the association between post-induction fludeoxyglucose F-18 (18F-FDG) positron emission tomography (PET)/computed tomography (CT) and patient outcomes (overall survival [OS] and progression-free survival [PFS]). (Primary Imaging Objective) II. To evaluate the association between baseline 18F-FDG PET/CT and patient outcomes (PFS and OS). (Secondary Imaging Objective) III. To compare overall survival with the addition of Bortezomib to consolidation DRd therapy among 18F-FDG PET/CT-positive and 18F-FDG PET/CT-negative subgroups. (Secondary Imaging Objective) IV. To evaluate the ability of baseline 18F-FDG PET/CT to predict post-induction depth of response as measured by MRD assessment. (Secondary Imaging Objective) V. To evaluate the ability of post-induction 18F-FDG PET/CT to predict MRD conversion post-consolidation. (Secondary Imaging Objective) VI. To utilize 18F-FDG PET/CT, standard risk factors and clinical data to identify distinct subgroups with differing patient outcomes (PFS and OS). (Exploratory Imaging Objective) VII. To compare the various qualitative 18F-FDG PET/CT criteria to determine which criteria yields superior risk stratification. (Exploratory Imaging Objective) OUTLINE: ARM A (INDUCTION): All patients receive standard induction therapy comprising the following: daratumumab subcutaneously (SC) on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7-9, lenalidomide orally (PO) daily on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity. After completion of standard induction therapy, patients are randomized to 1 of 2 arms. ARM B: CONSOLIDATION: Patients receive bortezomib SC on days 1, 8, and 15, daratumumab SC on day 1, lenalidomide PO daily on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive lenalidomide PO daily on days 1-21 and daratumumab SC on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM C: CONSOLIDATION: Patients receive daratumumab SC on day 1, lenalidomide PO daily on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive lenalidomide PO daily on days 1-21, and daratumumab SC on day 1. Cycles repeats every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, every 6 months if 2-5 years from study entry, then annually for up to 15 years from study entry.

Colon Adjuvant Chemotherapy Based on Evaluation of Residual Disease

Currently, there are no biomarkers validated prospectively in randomized studies for resected colon cancer to determine need for adjuvant chemotherapy. However, circulating tumor DNA (ctDNA) shed into the bloodstream represents a highly specific and sensitive approach (especially with serial monitoring) for identifying microscopic or residual tumor cells in colon cancer patients and may outperform traditional clinical and pathological features in prognosticating risk for recurrence. Colon cancer patients who do not have detectable ctDNA (ctDNA-) are at a much lower risk of recurrence and may not need adjuvant chemotherapy. Furthermore, for colon cancer pts with detectable ctDNA (ctDNA+) who are at a very high risk of recurrence, the optimal adjuvant chemotherapy regimen has not been established. We hypothesize that for pts whose colon cancer has been resected, ctDNA status may be used to risk stratify for making decisions about adjuvant chemotherapy.